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1,600 | 27,917,518 | This systematic review suggests that age is not a limiting factor for dental implant therapy | The aim of this systematic review was to evaluate implant loss in younger and older patients . | Background . Short implants have become popular in the reconstruction of jaws , especially in cases with limited bone height . Shorter implants , those with locking tapers and plateau root shapes , tend to have longer survival times . We retrospectively investigated the cumulative survival rates of Bicon short implants ( < 8 mm ) according to patient variables over a 5-year period . Material s and Methods . This study included 111 consecutively treated patients with 371 implants supporting fixed or removable prosthetics . Data were evaluated to acquire cumulative survival rates according to gender , age , tobacco use , surgical procedure , bone quality , and restoration type . Statistics were performed using chi-square , Mann-Whitney , and Kruskal Wallis H tests . Results . The survival rate was 97.3 % with , on average , 22.8 months of follow-up . Patients older than 60 years had higher failure rate than the other age groups ( P < 0.05 ) . Placed region , age , and bone quality had adverse effects on survival rate in the < 8 mm implant group with statistically significant difference ( P < 0.05 ) . Conclusions . Approximately 23-month follow-up data indicate that short implants with locking tapers and plateau-type roots have comparable survival rates as other types of dental implants . However , due to limitations of study , these issues remain to be further investigated in future r and omized controlled clinical trials BACKGROUND Health risks associated with smoking have been exhaustively documented and include increased incidence of periodontal disease , greater risk of osteitis following oral surgery , and compromised wound healing due to hypoxia . Information related directly to dental implants , although limited , points to higher rates of implant failures among smokers than non-smokers . This paper reports on long-term clinical outcomes of osseointegrated dental implants placed in smokers and non-smokers in a longitudinal clinical study of endosseous dental implants . METHODS In 1990 , the Dental Implant Clinical Research Group ( DICRG ) of the Department of Veterans Affairs ( DVA ) launched an 8-year , r and omized , prospect i ve clinical study of more than 2,900 endosseous dental implants in more than 800 patients at 32 study centers . Confounding variables , including smoking patterns , were recorded . For this report , new follow-up data were analyzed for two groups : 1 ) current smokers and 2 ) those who never smoked combined with those who quit . Most of the variables recorded for each implant were screened on a univariate basis as possible predictors associated with implant survival/failure . Those with P values less than 0.15 and those likely to be a factor of clinical importance were placed in a logistic regression equation and analyzed for a simultaneous effect on survival . A step-wise procedure was used to eliminate those variables that showed the least significance , until only those variables with a Wald chi-square of significance in the presence of others remained . The effects of clustering within patients and of unbalanced distribution within hospitals were st and ardized to facilitate analysis of influence of demographic variables . The GEE analysis was performed with the patient as the primary cluster . RESULTS Current data do not support earlier findings that smoking contributes to early implant failure ( placement to uncovering ) . A trend of greater failures in smokers appeared between the time after uncovering and before insertion of the prosthesis . Hydroxyapatite (HA)-coated implants had significantly lower failure rates . For the entire 3-year period , overall failures were significantly higher for smokers than non-smokers . CONCLUSIONS Results suggest that increased implant failures in smokers are not the result of poor healing or osseointegration , but of exposure of peri-implant tissues to tobacco smoke . Data also suggest that detrimental effects may be reduced by : 1 ) cessation of smoking ; 2 ) the use of preoperative antibiotics ; and 3 ) the use of HA-coated implants PURPOSE To evaluate aged partially and fully edentulous patients who received dental implants and were maintained over time . Further , to determine how the partially and edentulous ageing population s ( 65 and above ) with dental implants maintain bone levels , proper oral hygiene , and perceive benefits of dental implants . MATERIAL S AND METHODS Since 1995 , patients receiving dental implants have been prospect ively entered into an Access-based computerized program ( Triton Tacking System ) . Patient demographics ( age , sex ) , bone quality , quantity , implant location , and type of surgery have been continuously entered into the data base . The data base was queried for patients receiving implants ( first stage ) between 66 and 93 years of age . Thirty-one patients were within this age group . Twenty-five patients returned to the clinic for periodontal and dental implant evaluation . The Periodontal Index was used to evaluate selected teeth in terms of probing depth , bleeding on probing , plaque accumulation , and mobility . Using NIH Image J , radiographs taken at second stage and last examination were measured for changes in interproximal bone levels . Once identified , each patient anomalously filled out an abbreviated quality of health life form . Due to small sample size , descriptive statistics were used to compare clinical findings . RESULTS Fifteen males ranging from 78 to 84 ( mean age 84 years ) years and 16 females from 66 to 93 ( mean age 83 years ) ( age range 66 - 93 ) were contacted by phone or mail and asked to return to our office for a re-examination . For this group , the first dental implants were placed in 1996 ( n = initial two implants ) and continuously recorded through 2013 ( n = last seven implants ) . Thirty-one patients received a total of 84 implants . Two patients were edentulous , and the remaining were partially edentulous . Four implants were lost . Between implant placement and 6- to 7-year interval , 13 patients with 40 implants had a cumulative survival rate of 94.6 % . Of the original group ( n = 33 ) , three were deceased , two were in nursing homes , and three could not be located . CONCLUSIONS Aged patients receiving dental implants had excellent implant survival rates , low periodontal disease index scores with minimal changes in interproximal bone levels . Results from this study indicate that patients with advanced age , in reasonably good health , have excellent implant survival rates , excellent quality of life scores , and can be maintained in good oral health BACKGROUND The placement of an implant into a fresh extraction socket has been identified as a reliable technique , allowing a reduction in the time needed for prosthetic rehabilitation . This treatment modality is widely reported in the scientific literature ; however , the long-term outcomes and the need for guided bone regeneration ( GBR ) are still topics of debate . The aim of this prospect i ve study is to evaluate the clinical and radiologic findings from the 10-year follow-up of immediately placed implants , with and without the GBR procedure . METHODS A total of 159 implants in 91 patients are included in this study ; 101 implants required a GBR procedure simultaneously with placement . All implants were used to support a single crown restoration . The clinical /radiographic measurements were repeated each year up to the 10-year follow-up . At the 10-year follow-up visit , the papilla index and the apico-coronal location of mid-buccal soft tissue positions were recorded . RESULTS The 10-year cumulative success rate was 91.8 % ( 87.9 % in the non-GBR group and 94.1 % in the GBR group ) . The clinical attachment level ( CAL ) measurements were stable throughout the study , and 82 % of the implants showed marginal bone loss ( MBL ) of 0.6 to 1.5 mm at the 10-year visit ; moreover , these two parameters did not show significant differences between the GBR and non-GBR groups . Seventy percent of the implant sites showed acceptable outcomes in terms of interproximal papilla . The facial gingival level was more apical in the non-GBR group than in the GBR group ( P < 0.05 ) . CONCLUSIONS The present prospect i ve clinical study shows that implants placed in fresh extraction sockets had a high cumulative success rate , namely 91.8 % after 10 years . No differences were detected in survival and success rate of implants whether GBR procedures were performed or not . The CAL , MBL , and marginal level of soft tissue measurements were stable throughout the 10-year evaluation OBJECTIVES The purpose of the present clinical study was to report on the clinical performance of screw-cylinder implants with special consideration of the survival rate of short implants . MATERIAL AND METHODS In this prospect i ve study with consecutive patient recruitment , Camlog screw-cylinder implants with a particle-blasted and acid-etched microstructured surface and a triple-cam tube-in-tube implant-abutment connection have been used only . Two groups of implants were evaluated : implants of 9 and 11 mm in length were considered short , those of 13 and 16 mm were considered long . Besides clinical and radiographic parameters , data of complications , patients ' subjective evaluation of treatment outcome , general medical history and smoking habits were recorded . RESULTS Three hundred and thirty-three Camlog screw-cylinder implants were inserted in 133 patients . One hundred and twenty-nine patients were available for follow-up , representing 325 implants . The median observation period was 33 months ( Q(25 % ) 26 ; Q(75 % ) 38 ) . After a maximum observation period of 55 months , the Kaplan-Meier-survival analysis revealed no significant difference between the mean survival probabilities of 98.3 % ( n=59 , patient-related ) of short implants , and of 95.7 % of long implants ( n=70 , patient-related ) ( P=0.162 ) . No significant difference was found between implant survival rates considering maxilla ( 98.7 % ) and m and ible ( 98.2 % ) . A stratified analysis of short implants revealed a significant influence of premature cover screw exposures ( P=0.02 ) and smoking ( P=0.008 ) on implant survival . These influences were not found significant for long implants . CONCLUSIONS The prognosis of short Camlog implants is comparable with that of long implants . Therefore , their clinical use instead of performance of sophisticated vertical augmentation procedures before installation of long implants might be considered as alternative treatment option . In smokers , the use of short implants should be considered cautiously , however . The risk of premature cover screw exposure should be minimized PURPOSE This 15-year prospect i ve study evaluated the success rate and preservation of the gingival margin of single implants placed in a flapless procedure loaded immediately after extraction or after a healing period . MATERIAL S AND METHODS Immediate flapless implant placement was performed in patients who fulfilled specified inclusion criteria . Implants were either immediately restored with a provisional crown or left unloaded ( received healing abutment only ) . Implant success and gingival margin levels were evaluated after implant placement and after 1 to 15 years . RESULTS A total of 305 healthy nonsmoking subjects ( 90 men , 215 women ) were treated with 430 immediate implants during a 15-year period ( December 1994 to December 2009 ) and monitored for 1 to 15 years . Two hundred seventy-five implants received an immediate provisional crown , and 155 received a healing abutment . The implant survival rate was 93.03 % ( ± 3.74 % ) . The immediate provisional helped to maintain the original gingival margin , although the implant survival rate was higher for implants that were not immediately restored ( 96.78 % ) than for the implants that were immediately restored with a provisional ( 90.9 % ) . CONCLUSIONS This 15-year prospect i ve study showed a favorable implant success rate related to the flapless immediate implant placement protocol with healing abutment placement or an immediate provisional crown to replace a single missing tooth PURPOSE The aim of this prospect i ve comparative study was to assess whether age has influence on peri-implant health in patients treated with m and ibular two-implant overdentures during a 10-year evaluation period . MATERIAL S AND METHODS A prospect i ve study was carried out with two groups of edentulous patients , viz a younger ( n = 52 ; mean age 45 years , 35 - 50 years ) and an older ( n = 53 ; mean age 68 years , 60 - 80 years ) group . In all patients , two dental implants were placed in the interforaminal region of the m and ible and after a 3-month healing period overdentures were fabricated . Clinical and radiographic parameters were evaluated immediately after completion of the prosthetic treatment , and after 1 , 5 and 10 years . Implant loss , plaque index , gingival index , bleeding index , and probing depth were assessed as clinical parameters . Peri-implant bone loss was assessed on dental radiographs made with a st and ardized long-cone technique with a direction device . RESULTS Implant survival after 10 years was 97.1 % and 93.4 % in the younger and older group , respectively . Ten-year scores of plaque , gingiva , and bleeding were between 0 and 1 for both groups ( possible scores 0 - 3 ) , and mean probing depth was 3 mm in both groups . Mean peri-implant bone loss after 10 years was 1.2 and 1.4 mm in the younger and older patients , respectively . No significant differences were observed between the groups . CONCLUSION Clinical performance of m and ibular two-implant overdentures is equally successful in younger and older patients This prospect i ve study evaluated the long-term performance of tapered screw implants placed in patients with a variety of potentially compromising clinical variables . Sixty patients were treated with 218 implants ; each case included one or more potential risk factors associated with increased rates of implant failure , peri-implant bone loss or clinical complications in the dental literature : short implants ( 23 % ) , comorbid conditions ( 25 % ) , maxillary implants ( 61 % ) , immediate loading ( 88.5 % ) , placement into extraction sockets ( 91 % ) , and partial edentulism ( 97 % ) . The implants were restored with a variety of prostheses . Marginal bone changes were calculated utilizing periapical radiographs taken at placement and at all subsequent appointments utilizing a st and ardized paralleling device and a 1-mm measurement grid . Mean clinical follow-up was 67.5 ( range : 1 - 94 ) months for implants and 60 ( range : 15 - 74 ) months for prostheses . Four implants failed to integrate and were immediately replaced by wide-diameter implants . Eight prostheses sustained porcelain fracture ( n = 7 ) or cement failure ( n = 1 ) and were replaced . No peri-implant marginal bone loss was observed for 98 % of the implants ; the remaining 2 % exhibited 1 mm of bone loss . Cumulative survival rates were 98.2 % for implants and 96.3 % for prostheses after 5 years of clinical loading . Concerns that tapered implant design s may be more prone to crestal bone loss than cylinder design s are unsupported by the results of this study . Tapered implants maintained integration and marginal bone levels despite the presence of one or more potentially compromising variables The purpose of this study was ( 1 ) to investigate denture satisfaction following the conversion of existing m and ibular complete dentures to implant overdentures ( IOD ) in very old edentulous patients who depend on help for activities of daily living and ( 2 ) to evaluate secondary end points , such as functional , structural , nutritional , and patient-centered aspects . For this r and omized clinical trial , 2 interforaminal short implants were placed in the intervention group ( n = 16 , 85.0 ± 6.19 yrs ) to retain m and ibular IODs ; the control group ( n = 18 , 84.1 ± 5.55 yrs ) received conventional relines . During the first year , no implant was lost ; however , 2 patients died . IODs proved more stable , and participants in the intervention group demonstrated significantly higher denture satisfaction as well as an increased oral health – related quality of life compared to the control group . Maximum voluntary bite force improved significantly with IODs , yet the chewing efficiency was not different between groups . Masseter muscle thickness increased with IODs , mainly on the preferred chewing side . Body mass index decreased in both groups , but the decline tended to be smaller in the intervention group ; blood markers and the Mini Nutritional Assessment did not confirm this tendency . These results indicate that edentulous patients who depend on help for activities of daily living may benefit from IODs even late in life ( Clinical Trial.gov NCT01928004 ) Implant prognoses for healthy elderly patients have been found to be comparable with those reported for younger patients . In 1991 , the Dental Implant Clinical Research Group initiated a prospect i ve , r and omized clinical study in cooperation with the Department of Veterans Affairs to investigate the influence of implant design , application , and site of placement on long-term clinical performance and crestal bone height . As a result of the large sample size and wide range of patient ages , the study provided an opportunity to determine if age correlates with implant survival . Interim analysis of 2,132 root form implants at uncovering on an implant , case , and patient basis suggests that implant survival does not appear to be influenced by age in the largely white , male sample . ( Implant Dent 1994;3:247–251 OBJECTIVES Osteoporosis is known to impair the process of implant osseointegration . The recent discovery that statins ( HMG-CoA reductase inhibitors ) act as bone anabolic agents suggests that statins can be used as potential agents in the treatment of osteoporosis . Therefore , we hypothesized that statins will promote osteogenesis around titanium implants in subjects with osteoporosis . MATERIAL AND METHODS Fifty-four female Sprague Dawley rats , aged 3 months old , were r and omly divided into three groups : Sham-operated group ( SHAM ; n=18 ) , ovariectomized group ( OVX ; n=18 ) , and ovariectomized with Simvastatin treatment group ( OVX+SIM ; n=18 ) . Fifty-six days after being ovariectomized ( OVX ) , screw-shaped titanium implants were inserted into the tibiae . Simvastatin was administered orally at 5 mg/kg each day after the placement of the implant in the OVX+SIM group . The animals were sacrificed at either 28 or 84 days after implantation and the undecalcified tissue sections were obtained . Bone-to-implant contact ( BIC ) and bone area ( BA ) within the limits of implant threads were measured around the cortical ( zone A ) and cancellous ( zone B ) bone regions . Furthermore , bone density ( BD ) of zone B in a 500 microm wide zone lateral to the implants was also measured . RESULTS There were no significant differences in BIC and BA measurements in zone A in any of the three groups at either 28 or 84 days after implantation ( P>0.05 ) . By contrast , in zone B , significant differences in the measurement of BIC , BA , and BD were observed at 28 and 84 days between all three groups . Bone healing decreased with lower BIC , BA , and BD around implant in OVX group compared with other two groups , and Simvastatin reversed the negative effect of OVX on bone healing around implants with the improvement of BIC , BA , and BD in zone B. CONCLUSION Osteoporosis can significantly influence bone healing in the cancellous bone around titanium implants and Simvastatin was shown to significantly improve the osseointegration of pure titanium implants in osteoporotic rats AIM To assess the failure and bone-to-implant contact rate of dental implants placed on osteoporotic subjects . METHODS Extensive examination strategies were created to classify studies for this systematic review . MEDLINE ( via PubMed ) and EMBASE data base were examined for studies in English up to and including May 2014 . The examination presented a combination of the MeSH words described as follow : " osteoporosis " or " osteopenia " or " estrogen deficiency " AND " implant " or " dental implant " or " osseointegration " . Assessment of clinical and /or histological peri-implant conditions in osteoporosis subjects treated with titanium dental implants . The examination included a combination of the MeSH terms described as follow : " osteoporosis " or " osteopenia " or " estrogen deficiency " AND " implant " or " dental implant " or " osseointegration " . RESULTS Of 943 potentially eligible articles , 12 were included in the study . A total of 133 subjects with osteoporosis , 73 subjects diagnosed with osteopenia and 708 healthy subjects were assessed in this systematic review . In these subjects were installed 367 , 205 , 2981 dental implants in osteoporotic , osteopenic and healthy subjects , respectively . The failure rate of dental implant was 10.9 % in osteoporotic subjects , 8.29 % in osteopenic and 11.43 % in healthy ones . Bone-to-implant contact obtained from retrieved implants ranged between 49.96 % to 47.84 % , for osteoporosis and non-osteoporotic subjects . CONCLUSION Osteoporotic subjects presented higher rates of implant loss , however , there is a lower evidence to strengthen or refute the hypothesis that osteoporosis may have detrimental effects on bone healing . Consequently , final conclusions regarding the effect of osteoporosis in dental implant therapy can not be made at this time . There are no r and omized clinical trial accessible for evaluation and the retrospective nature of the evaluated studies shall be taken in account when interpreting this study PURPOSE The aim of this study was to evaluate the survival rate of immediately provisionalized implants with up to 5 years follow-up . MATERIAL S AND METHODS The study consisted of 226 patients , 113 consecutive patients with immediately provisionalized dental implants ( cases ) and 113 r and omly selected , age- , gender- , and implant position-matched controls with conventional late implant loading . Survival rate and incidence of complications were recorded . RESULTS Follow-up ranged from 6 to 60 months . Smoking was reported by 20.8 % of patients . Maxillary incisors and m and ibular lateral incisors were the most common areas for implant placement . Conventionally loaded implants were narrower ( p = .03 ) and shorter ( p = .001 ) . Immediate implantation into a fresh extraction socket was performed in 69 % of the cases and in 36.3 % of the controls ( p = .001 ) . Implant survival rate was 96.5 % . Of the eight failed implants , six were immediately provisionalized and two were conventionally loaded . No statistically significant difference was found in survival rates between groups ( p > 0.05 ) . Five of the failed implants ( case group ) were immediately loaded implants placed in fresh extraction sockets . CONCLUSION Immediate implant provisionalization achieved similar high success rates compared with the conventional , delayed approach . As immediate implant provisionalization is mainly desired in the anterior region , the high success rates are encouraging |
1,601 | 20,614,426 | House dust mite impermeable bedding as an isolated intervention is unlikely to offer clinical benefit .
Trials to date have on the whole been small and of poor method ological quality , making it difficult to offer any definitive recommendations on the role , if any , of house dust mite avoidance measures in the management of house dust mite sensitive perennial allergic rhinitis .
The results of these studies suggest that use of acaricides and extensive bedroom-based environmental control programmes may be of some benefit in reducing rhinitis symptoms and , if considered appropriate , these should be the interventions of choice .
Isolated use of house dust mite impermeable bedding is unlikely to prove effective | BACKGROUND This is an up date of a Cochrane Review first published in The Cochrane Library in Issue 4 , 2001 and previously up date d in 2003 and 2007.It is estimated that in developed countries approximately 30 % of the general population suffer from one or more allergic disorders , of which allergic rhinitis is particularly common .
Perennial rhinitis is most often due to allergy to the house dust mite .
In such patients house dust mite avoidance is logical , but there is considerable uncertainty regarding the efficacy and effectiveness of interventions design ed to reduce dust mite exposure .
OBJECTIVES To assess the benefit ( and harm ) of measures design ed to reduce house dust mite exposure in the management of house dust mite sensitive allergic rhinitis . | A r and omized comparison group pretest-posttest experimental design was used to quantitatively determine the effects of environmental control measures on patients with allergic rhinitis . Environmental controls included wrapping the mattress with a vinyl cover , washing the top bedding cover with 55 degrees C hot water every two weeks , removal of soft furniture , and wet cleaning of the bedroom floor every day . Thirty subjects were r and omly assigned to experimental and control groups . The amount of house dust mites in dust sample s collected from the bedroom floor , bedding and mattress , as well as the nasal symptoms of patients , were measured twice at one-month intervals . A significant decrease in house dust mites in dust sample s and relief in patients ' nasal symptoms were observed in the experimental group who had environmental controls Background : Environmental control has been put forward as an integral part of the management of house dust mite ( HDM ) allergy in sensitized patients . To vali date this statement allergic disorders involved in HDM allergy – allergic asthma , rhinitis and atopic eczema/dermatitis syndrome ( AEDS ) – should be taken together and studied in terms of the efficacy of environmental control . Because a generic quality of life question naire exceeds the border of disease , this may be used as major outcome parameter BACKGROUND Encasing bedding in impermeable covers reduces exposure to house-dust mites , but the clinical benefit of this intervention as part of mite-avoidance measures for patients with allergic rhinitis is not known . We performed a multicenter , r and omized , placebo-controlled trial of one year of use of impermeable bedding covers in the bedrooms of patients with rhinitis who were sensitized to house-dust mites to determine the effects on the signs and symptoms of disease . METHODS Three participating university medical centers enrolled 279 patients with allergic rhinitis who were r and omly assigned to receive impermeable or non-impermeable ( control ) covers for their mattress , pillow , and duvet or blanket . At the start of the study , all participants received information on general allergen-avoidance measures . The severity of rhinitis was measured on a rhinitis-specific visual-analogue scale and by means of a daily symptom score and nasal allergen provocation testing . We also measured the concentrations of Dermatophagoides pteronyssinus ( Der p1 ) and D. farinae ( Der f1 ) in dust from patients ' mattresses , bedroom floors , and living-room floors at base line and after 12 months as a measure of the efficacy of the intervention . RESULTS A total of 232 patients completed the study . There was a significant reduction in Der p1 and Der f1 concentrations in the mattresses of the impermeable-cover group , whereas there was no significant reduction in the control group . However , there was no significant effect on the clinical outcome measures . Analyses of subgroups defined according to age , level of exposure , type and severity of sensitization , or characteristics of the patient 's home had similar results . CONCLUSIONS Mite-proof bedding covers , as part of a structured allergy-control program , reduced the level of exposure to mite allergens . Despite the success of the intervention , this single avoidance measure did not lead to a significant improvement of clinical symptoms in patients with allergic rhinitis A double blind , r and omized , comparative study versus placebo , was done during 6 months in 32 children , aged 4 - 12 years , who suffer from either allergic asthma or rhinitis or both , slept in a bedroom rich in dust mite , have well documented allergy solely to house dust mite ( H.D.M. ) , and a condition severe enough to require continuous medication . After thorough cleaning , their bedrooms were sprayed on day 0 and day 90 with the total content of a canister containing either Acardust or Placebo . Rooms were cleaned regularly throughout the study period . Each child completed an individual daily score card ( scales from 0 - 3 ) for asthma , and rhinitis symptoms , medication taken , and any additional symptoms . Peak flow was recorded twice weekly . All the children were examined every month ( at the clinic ) when also PFF , FEVI , doctor 's and patient 's opinion of clinical symptoms were recorded according to the same scale ( 0 - 3 ) and dust sample s from child 's bedroom were examined for H.D.M. antigen content . At day 0 , 90 and 180 , total IgE and dust mite specific IgE determination was done . At the end of the study , patient 's and doctor 's opinion about the spray 's efficacy were recorded on a scale from 0 - 3 . The results were in favor of Acardust for asthma , according to patient 's opinion ( p = 0.001 ) , doctor 's opinion ( p = 0.04 ) and individual score cards ( p = 0.03 ) , and for nasal secretion ( p = 0.01 ) , sneezing and lacrimation ( p = 0.02 ) ; concurrent medication dropped significantly ( p = 0.01 ) in the Acardust group . No side-effects were reported . We consider Acardust a safe and valuable preventive treatment in H.D.M. allergy BACKGROUND Data for trends in prevalence of asthma , allergic rhinoconjunctivitis , and eczema over time are scarce . We repeated the International Study of Asthma and Allergies in Childhood ( ISAAC ) at least 5 years after Phase One , to examine changes in the prevalence of symptoms of these disorders . METHODS For the ISAAC Phase Three study , between 2002 and 2003 , we did a cross-sectional question naire survey of 193,404 children aged 6 - 7 years from 66 centres in 37 countries , and 304,679 children aged 13 - 14 years from 106 centres in 56 countries , chosen from a r and om sample of schools in a defined geographical area . FINDINGS Phase Three was completed a mean of 7 years after Phase One . Most centres showed a change in prevalence of 1 or more SE for at least one disorder , with increases being twice as common as decreases , and increases being more common in the 6 - 7 year age-group than in the 13 - 14 year age-group , and at most levels of mean prevalence . An exception was asthma symptoms in the older age-group , in which decreases were more common at high prevalence . For both age-groups , more centres showed increases in all three disorders more often than showing decreases , but most centres had mixed changes . INTERPRETATION The rise in prevalence of symptoms in many centres is concerning , but the absence of increases in prevalence of asthma symptoms for centres with existing high prevalence in the older age-group is reassuring . The divergent trends in prevalence of symptoms of allergic diseases form the basis for further research into the causes of such disorders This study was design ed to assess the effectiveness of a high-efficiency particulate air ( HEPA ) filter in alleviating allergic respiratory symptoms . Thirty-two patients were studied who had symptomatic perennial rhinitis and /or asthma during the fall and winter months and had a positive skin test with house dust or house dust -- mite extract . An ENVIRACAIRE room air cleaner was placed in the bedroom for 8 weeks . In a r and om manner , the active filter was used for 4 weeks and a blank filter for 4 weeks . There was an average 70 % reduction in the particulate matter greater than or equal to 0.3 micron with the HEPA filter . In a double-blind design , results were assessed by analysis of the patients ' symptom/medication scores and subjective evaluation . For the total study , there was no difference in the total symptom/medication scores or individual symptom scores during the placebo and active-filter periods . Analysis of the last 2 weeks of each filter period in which respiratory infection was absent demonstrated definite differences in total and individual symptoms , suggesting active-filter benefit . Patients ' subjective responses also suggested benefit from the filter . The overall impression is that the HEPA filter can reduce allergic respiratory symptoms UNLABELLED The aim of this intervention study was to identify any health improvements in the upper and lower airways of office workers after the installation of local electrostatic air cleaners . Eighty persons with airways symptoms were recruited and r and omly assigned to an intervention or control group . Half of the air cleaners had a non-functioning electrostatic unit . Both participants and field research ers were blinded to the group status . Subjective symptoms were recorded using a question naire , and indexes calculated for general , irritation and skin symptoms . Objective respiratory health indicators were recorded , with acoustic rhinometry and peak expiratory flow ( PEF ) meters . In the intervention group there was a decrease in mean dust concentration from 65 to 35 microg/m(3 ) , and a reduction from 57 to 47 microg/m(3 ) in the control group ( P < 0.05 for difference in decline ) . The reduction was observed for all particles sizes . The irritation and general symptom indices decreased in both groups , but there was no improvement in the intervention group , compared with the control group . Median PEF increased 3 ml/s in the intervention group , and decreased 4 ml/s in the control group . The adjusted odds ratio for an increase above the 70th percentile was 5.7 ( 95 % CI 1.0 - 32 ) . PRACTICAL IMPLICATION S Electrostatic air cleaners can reduce the dust concentration effectively in the office environment . Small , medium and large sized particles can be reduced by approximately 50 % , relatively most effectively for the respirable particles . However , the air cleaners tested in this study produced an annoying fan noise . Cleaning efficiency and noise data should be given consideration before installation . This experimental field study suggests that office workers with airways symptoms may benefit from installation of local electrostatic air cleaners N-(3,4-dimethoxycinnamoyl ) anthranilic acid ( N-5 ' ) , a new orally useable mast cell stabilizer , was investigated for its efficacy , safety and usefulness in the treatment of 302 patients with perennial nasal allergy by an intergroup , double-blind comparative test using disodium cromoglycate ( DSCG ) and an inactive placebo as control . The results indicated that N-5 ' , as a mild mast cell stabilizer , was comparable to DSCG in efficacy and minimum in side effect The efficacy of an air‐cleaning device equipped with a high efficiency particulate air ( HEPA ) filter ( without further avoidance measures ) was studied in patients allergic to house dust mite . The effects of the air‐cleaner on indoor Dermatophagoides sp. levels , symptom score and bronchial hyperresponsiveness in nine mite‐allergic patients were assessed using a cross‐over controlled study . No significant effect was demonstrated on indoor Dermatophagoides sp. levels when comparing the period of air‐cleaner activity ( 2 months ) with the control period ( 2 months ) . The Dermatophagoides sp. levels in the houses studied were lower than the risk level for asthmatic attacks , making it difficult to assess any effect on asthma ; however , neither bronchial hyperresponsiveness nor rhinitis symptom score were changed by air‐cleaner activity . During the trial period , however the mean level of Dermatophagoides sp. allergen in the houses changed spontaneously from 4.4 Hg/g ( mean level in the first 2 trial months ) to 1 . 75 μg/g of dust ( second 2 months ) ( P < 0.05 ) . Owing to this change , the mean rhinitis symptom score also decreased ( P < 0.05 ) , even if no significant correlation was demonstrated ( r = 0.4 P= 0.089 ) . HEPA filter air‐cleaners appear insufficient as substitutes for st and ard avoidance measures in mite allergic patients Inheritance and allergen exposure are key factors in the development and the course of atopic allergy , expressed as conjunctivitis , rhinitis , asthma or dermatitis . This study concerns the clinical significance of mite and mite‐allergen avoidance measures based on intensive cleaning with acaricide ( solidified benzylbenzoate ) added ( 10 dwellings ) , and without biocidal activity ( 10 other homes ) as a control in a double‐blind trial with matched pairs . Twenty subjects with persisting rhinitic complaints were selected . They lived in 20 different dwellings and were ail sensitized to pyroglyphid mites ; 12 of them were also sensitized to stored product miles ( Acari ) . Daily symptoms and medication score , guanine and dust exposure , total and mite‐specific IgE in serum , eosinophilia in the blood and in the nasal smear , intracutaneous tests with house dust mite and storage mite extracts were compared in both pairs and groups . Acarological data , physiochemical aspects and exposure assessment are discussed in detail elsewhere . Symptom scores dropped significantly , as did the total IgE and exposure to dust and mite products in the acaricidal cleaner treatment group . After 1 year , the daily symptoms median was 47 % ( P= 0.025 ) , total IgE was 38 % ( P=0.0049 ) , and exposure to dust and mite products ( guanine exposure ) was 53 % ( P= 0.0449 ) better or lower than in the controls . Intensive cleaning , without acaricidal treatment performed twice a year , result ed in clinical improvement in four out of 10 subjects , of whom none became free of complaints . In the Acarosan treatment group ( cleaning+ benzylbenzoate ) eight out of 10 subjcets improved , in three cases subjective symptoms disappeared . The conclusion is that mite avoidance in homes can be carried out successfully with a special acaricidal cleaning formulation Acarosan We report on the mechanisms , the environmental changes and patient compliance with regard to conventional and new dust and mite avoidance measures to prevent allergic symptoms caused by mite allergens , taking into account both allergen contamination and the developmental success of pyroglyphid Acari . Twenty patients with persisting rhinitic complaints were selected and matched . Although the patients had performed some conventional dust and mite avoidance measures ( patient compliance was 90 % ) , the dwellings proved to be a stimulus for mite development . Moisture problems due to faulty construction and excessive moisture production were common . Since humidity conditions could not be changed at short notice , the 20 homes were subjected to the new variants of mite allergen avoidance based on intensive cleaning without ( control ) and with an acaricide incorporated ( acaricidal cleaner [ Acarosan ] ) . After the carrying out of conventional avoidance measures , these patients still had allergic symptoms , and dust from only 23 to 52 % of their textile objects was under the proposed guanine ( mite faeces indicator ) risk level . Only the acaricidal cleaner was able to decrease the allergenic mite load ( and the burden of the patients ) significantly in this 12 month period . With respect to mite‐extermination , acaricidal cleaning was 88 % better than intensive cleaning . Reduction of guanine was 38 % better in the Acarosan treatment group |
1,602 | 28,375,548 | One adverse event was reported by one study .Exercise-based cardiac rehabilitation improves exercise capacity , but exercise was found to have no impact on health-related quality of life in the short-term ( median 12 weeks follow-up ) , in heart transplant recipients whose health is stable .
There was no evidence of statistical heterogeneity across trials for exercise capacity and no evidence of small study bias .
We found moderate quality evidence suggesting that exercise-based cardiac rehabilitation improves exercise capacity , and that exercise has no impact on health-related quality of life in the short-term ( median 12 weeks follow-up ) , in heart transplant recipients . | BACKGROUND Heart transplantation is considered to be the gold st and ard treatment for selected patients with end-stage heart disease when medical therapy has been unable to halt progression of the underlying pathology .
Evidence suggests that aerobic exercise training may be effective in reversing the pathophysiological consequences associated with cardiac denervation and prevent immunosuppression-induced adverse effects in heart transplant recipients .
OBJECTIVES To determine the effectiveness and safety of exercise-based rehabilitation on the mortality , hospital admissions , adverse events , exercise capacity , health-related quality of life , return to work and costs for people after heart transplantation . | BACKGROUND Hypertension is the most prevalent comorbidity after heart transplantation ( HT ) . Exercise training ( ET ) is widely recommended as a key non-pharmacologic intervention for the prevention and management of hypertension , but its effects on ambulatory blood pressure ( ABP ) and some mechanisms involved in the pathophysiology of hypertension have not been studied in this population . The primary purpose of this study was to investigate the effects of ET on ABP and arterial stiffness of HT recipients . METHODS 40 HT patients , r and omized to ET ( n = 31 ) or a control group ( n = 9 ) underwent a maximal grade d exercise test , 24-hour ABP monitoring , and carotid-femoral pulse wave velocity ( PWV ) assessment before the intervention and at a 12-week follow-up assessment . The ET program was performed thrice-weekly and consisted primarily of endurance exercise ( 40 minutes ) at ~70 % of maximum oxygen uptake ( Vo2MAX ) . RESULTS The ET group had reduced 24-hour ( 4.0 ± 1.4 mm Hg , p < 0.01 ) and daytime ( 4.8 ± 1.6 mm Hg , p < 0.01 ) systolic ABP , and 24-hour ( 7.0 ± 1.4 mm Hg , p < 0.001 ) daytime ( 7.5 ± 1.6 mm Hg , p < 0.001 ) and nighttime ( 5.9 ± 1.5 mm Hg , p < 0.001 ) diastolic ABP after the intervention . The ET group also had improved Vo2MAX ( 9.7 % ± 2.6 % , p < 0.001 ) after the intervention . However , PWV did not change after ET . No variable was changed in the control group after the intervention . CONCLUSIONS The 12-week ET program was effective for reducing ABP but not PWV in heart transplant recipients . This result suggests that endurance ET may be a tool to counteract hypertension in this high-risk population In heart transplant ( HTx ) recipients , there has been reluctance to recommend high‐intensity interval training ( HIIT ) due to denervation and chronotropic impairment of the heart . We compared the effects of 12 weeks ' HIIT versus continued moderate exercise ( CON ) on exercise capacity and chronotropic response in stable HTx recipients > 12 months after transplantation in a r and omized crossover trial . The study was completed by 16 HTx recipients ( mean age 52 years , 75 % males ) . Baseline peak oxygen uptake ( VO2peak ) was 22.9 mL/kg/min . HIIT increased VO2peak by 4.9 ± 2.7 mL/min/kg ( 17 % ) and CON by 2.6 ± 2.2 mL/kg/min ( 10 % ) ( significantly higher in HIIT ; p < 0.001 ) . During HIIT , systolic blood pressure decreased significantly ( p = 0.037 ) with no significant change in CON ( p = 0.241 ; between group difference p = 0.027 ) . Peak heart rate ( HRpeak ) increased significantly by 4.3 beats per minute ( p = 0.014 ) after HIIT with no significant change in CON ( p = 0.34 ; between group difference p = 0.027 ) . Heart rate recovery ( HRrecovery ) improved in both groups with a trend toward greater improvement after HIIT . The 5‐month washout showed a significant loss of improvement . HIIT was well tolerated , had a superior effect on oxygen uptake , and led to an unexpected increase in HRpeak accompanied by a faster HRrecovery . This indicates that the benefits of HIIT are partly a result of improved chronotropic response Background Aerobic exercise training improves vasodilatory capacity of peripheral resistance vasculature and modifies plasma proinflammatory markers in chronic heart failure patients . It is , however , currently unknown whether aerobic exercise has a similar effect in heart transplant recipients ( HTR ) . Design and Methods Eight weeks after transplantation , 14 HTR were r and omly assigned to 12 weeks of supervised aerobic exercise training ( TRAINED ; n = 8) or attention-time control ( CONTROL ; n = 6 ) in addition to posttransplantation medical care . Peak forearm blood flow and calf blood flow ( CBF ) during reactive hyperemia after 5 min of limb ischemia was used as a measure of endothelium-dependent vasodilation of limb resistance arteries . Plasma C-reactive protein , interleukin-6 ( IL-6 ) , tumor necrosis factor-alpha ( TNF-α ) , soluble intercellular adhesion molecule-1 ( sICAM-1 ) , and exercise capacity were measured at baseline and again after 12 weeks in both groups . Results Peak CBF increased 22 % in the TRAINED ( 25.9±5.8 - 31.6±7.9 ml/min/100 ml , P<0.05 ) , but there was no change in peak CBF after 12 weeks in CONTROL . Plasma C-reactive protein , IL-6 , TNF-α , sICAM-1 did not change in TRAINED , but there was a significant increase in TNF-α ( 1.66±1.02 vs. 3.07± 1.10 pg/ml , P < 0.05 ) , and sICAM-1 ( 205.9±59.1 vs. 245.0 ± 47.9 ng/ml , P<0.01 ) in CONTROL after 12 weeks . Furthermore , exercise test duration improved 51.7 % ( P<0.01 ) and there was a trend toward an increase in peak VO2 ( P = 0.05 ) in TRAINED after 12 weeks but neither changed in CONTROL . Conclusion A program of supervised aerobic exercise improves endothelium-dependent vasodilation of the calf , but not forearm resistance arteries , and may attenuate a progressive increase in selected proinflammatory markers in HTR Aim To evaluate the effects of home- and hospital-exercise programs on exercise capacity and chronotropic variables in patients with heart transplantation . Methods Forty patients were r and omized into two groups either hospital- or home-based exercise program . The patients were compared , before and after the rehabilitation program , with respect to maximal oxygen uptake ( pVO2 ) , chronotropic variables [ heart rate reserve ( HRRe ) , heart rate recovery ( HRR1 ) , and chronotropic response index ( CRI ) ] and Duke Treadmill Score ( DTS ) . Results Hospital-based exercise group has shown a significant recovery in post-exercise pVO2 ( pre-exercise 16.73 ± 3.9 ml/kg/min , post-exercise 19.53 ± 3.89 ml/kg/min , P = 0.002 ) and DTS ( pre-exercise 4.74 ± 1.17 , post-exercise 5.61 ± 1.11 , P = 0.002 ) . A significant recovery in favor of the hospital-based exercise group was found in HRRe ( pre-exercise 26.9 ± 14.6 , post-exercise 34.6 ± 14.6 , P = 0.01 ) . No significant change was observed in HRR1 ( pre-exercise −1.38 ± 1.04 , post-exercise −1.21 ± 1.89 , P = 0.49 ) and CRI ( pre-exercise 0.44 ± 0.23 , post-exercise 0.48 ± 0.20 , P = 0.15 ) in hospital-based exercise group . No significant change was observed in any parameters of home-based group ( P > 0.05 ) . Conclusion A significant recovery was observed both in the functional capacity and the chronotropic response in hospital-based exercise program . Exercise programs that are planned to be performed under supervision in rehabilitation units are useful for the patients with heart transplant in terms of the exercise capacity and chronotropic variables OBJECTIVE To compare the effects of two physical therapy exercise in-hospital programs in pulmonary function and functional capacity of patients in the postoperative period of heart transplantation . METHODS Twenty-two heart transplanted patients were r and omized to the control group ( CG , n=11 ) and training group ( TG , n=11 ) . The control group conducted the exercise program adopted as routine in the institution and the training group has had a protocol consisting of 10 stages , with incremental exercises : breathing exercises , resistance training , stretching and walking . The programs began on the first day after extubation and stretched until hospital discharge . Assessed pulmonary function , distance walked in six minutes walk test ( 6MWT ) and peripheral muscle strength by one repetition maximum test ( 1RM ) . RESULTS Similar behavior was observed between the two groups treated , with statistically significant increases between the first and second test of the following variables : FVC ( 59 % in CG and 35.2 % in TG ) ; MIP ( 8.6 % in CG and 53.5 % in TG ) , MEP ( 28.8 % in CG and 40.7 % in TG ) and 6MWT ( 44.5 % in CG and 31.4 % in TG ) . There was an increase of peripheral strength by 1RM test , over time , to the muscle groups of the elbow flexors , shoulder flexors , hip abductors and knee flexors . CONCLUSION Heart transplant patients benefit from exercise programs in hospital , regardless of the program type applied . A new training proposal did not result in superiority compared to routine programme applied . Exercise protocol s provided improves in ventilatory variables and functional capacity of this population The aim of the review was to assess the effect of patient education in ischaemic heart disease . Thirteen r and omised controlled trials of moderate to good quality including 68,556 patients were selected . The effect on mortality , cardiac morbidity , hospitalisation and health-related quality of life was assessed and only non-significant tendencies of effect were found . The authors of the review nevertheless conclude that the review supports current rehabilitation programmes that include patient education . Further research in patient education , especially concerning the most effective methods of education delivery , is needed BACKGROUND Heart transplantation normalizes central hemodynamics , but endothelial dysfunction persists after transplantation . METHODS To investigate the effects of aerobic exercise on arterial function , oxidative stress , lipid profile , and sympathetic nervous system activity , 20 heart transplant recipients ( age , 54.3 + /- 9.1 years ; 17 men , 3 women ) were r and omly assigned to 12 weeks of supervised treadmill exercise ( Trained ; n = 10 ) or st and ard medical care ( Control ; n = 10 ) . Supervised exercise was initiated at 8 weeks after transplant . Brachial artery reactivity was assessed using flow-mediated dilation . RESULTS The VO2 peak increased 26 % in the Trained patients ( 15.4 + /- 4.3 vs 19.4 + /- 5.5 ml/kg/min ; p < or = 0.05 ) but did not change in the Controls ( 16.2 + /- 5.2 vs 16.8 + /- 2.8 ml/kg/min ; p > or = 0.05 ) . Brachial artery flow-mediated dilation ( 10.1 % + /- 6.1 % vs 9.6 % + /- 6.2 % ) and absolute brachial diameter ( 0.48 + /- 0.22 vs 0.42 + /- 0.24 mm ) did not change in Trained patients , but brachial flow-mediated dilation ( 10.5 % + /- 2.8 % vs 7.9 % + /- 5.1 % ) and the absolute change in brachial diameter ( 0.48 + /- 0.16 vs 0.36 + /- 0.24 mm ) decreased significantly ( p < or = 0.05 ) in the Control patients . Resting norepinephrine decreased significantly ( p < or = 0.05 ) after training ( 0.32 + /- 0.19 vs 0.22 + /- 0.22 ng/ml ) , but there was a nonsignificant trend toward increased norepinephrine in the Controls ( 0.26 + /- 0.17 vs 0.53 + /- 0.41 ng/ml ; p = 0.07 ) . The lipid profile and marker of oxidative stress did not differ between the groups before or after the intervention . CONCLUSIONS To our knowledge , this is the first prospect i ve , r and omized study to investigate the effects of heart transplantation and aerobic exercise on peripheral artery function in the same cohort of heart transplant recipients . Brachial artery flow-mediated dilation increased early in the post-operative period . Aerobic exercise preserved but did not improve brachial artery flow-mediated dilation . Heart transplant recipients who did not participate in supervised exercise showed a progressive decline in brachial artery flow-mediated dilation Longterm treatment after heart transplantation ( HTX ) improves survival , although the quality of life and exercise tolerance decreased continuously between one and ten years after transplantation . The role of physical exercise and psychological support in longterm treatment after HTX has not been determined . We analyzed the effects of a one year outpatient rehabilitation program in combination with a home based , computer assisted training program on exercise capacity , coronary risk factors and quality of life . 20 heart transplant recipients in an intervention group and 12 patients after HTX in a control group participated in the study ( IG ( CG ) ; 5.1±2.2 ( 4.5±2.3 ) years after HTX ; age : 55±7 ( 54±8 ) years ; body mass index : 28.3±1.0 ( 28.7±0.9 ) kg·m–2 ) . Before and after the intervention , maximum and constant load exercise capacity , and self-reported quality of life were evaluated . The 12 month intervention period included 10 days of exercise testing as well as medical and psychological support . Furthermore , the IG group performed a computer-assisted and controlled home ergometer training every second day . After one year with 114±18 exercise training sessions , maximum oxygen consumption increased in the IG from 18.8±4.2 to 20.1±4.2 ml · min–1 · kg–1 ( p<0.05 ; CG 19.3± 4.5 to 18.5±2.8 ml·min– 1 · kg–1 ; p<0.01 IG vs CG ) . In the IG , lower back pain , body fat , and blood pressure were all reduced , while the self-reported quality of life , endurance exercise capacity and HDL cholesterol were increased . No significant changes occurred in the control group . When initiated years after heart transplantation , longterm rehabilitation reduced coronary risk factors and significantly improved both the subjects ’ quality of life , as well as a near to normal capacity for physical work . Bei gesteigerten Überlebensraten nach Herztransplantation ( HTX ) ist die subjektive Lebensqualität und Leistungsfähigkeit i m Langzeitverlauf reduziert , einhergehend mit erhöhten kardiovaskulären Risikoparametern . Ziel der prospektiven Studie war die Entwicklung und Evaluierung eines Modells zur Phase III Rehabilitation Herztransplantierter i m Langzeitverlauf , um in Ergänzung zur etablierten medizinischen Nachsorge Lebensqualität , Gesundheitsverhalten und Risikosituation zu verbessern . Bei 20 Patienten der Interventions - bzw . 12 Patienten der Kontrollgruppe ( IG ( KG ) ) ; 5,1±2,2 ( 4,5±2,3 ) Jahre nach HTX ; Alter : 55±7 ( 54±8 ) Jahre ; BMI : 28,3±1,0 ( 28,7±0,9 ) kg·m–2 ) wurde vor und nach der Intervention bzw . Kontrollphase jeweils eine Ergospirometrie durchgeführt , die subjektive Lebensqualität mit dem PLC-Fragebogen sowie die kardialen Risikoparameter untersucht . Intervention : Die IG erhielt an 10 Tagen , verteilt über 12 Monate psychologische und sportmedizinische Beratungen sowie Ergometerausdauertests . Auf der Basis der Testergebnisse wurde für die IG ein fernüberwachtes Heimergometertraining jeden 2 . Tag über 30 min individuell gesteuert . Die Kontrollgruppe erhielt das etablierte Nachsorgeprogramm . Nach einem Jahr und 114±18 Heimtrainingseinheiten stieg die Ausdauerleistung in der IG bei unveränderter Herzfrequenz von 46±12 auf 66±16 W ( + 43 % , p<0,01 ) . In den Stufentests zeigte die IG Verbesserungen der maximalen Leistung ( 102±23 auf 114±25 W ; p<0,01 ; KG : 108±30 und 107±23 W ) bei gleicher maximaler Herzfrequenz . Body-Mass-Index , Körperfettanteil , Blutdruck , HDL-Cholesterin sowie die subjektive Lebensqualität in physischen Dimensionen waren nach der Jahresmaßnahme nur in der IG signifikant verbessert . 5 Jahre nach HTX führt ein ambulantes Rehabilitationsprogramm zur Verbesserung bzw . Normalisierung der Lebensqualität , der Leistungsfähigkeit und der kardiovaskulären Risikoparameter BACKGROUND Growing evidence in long-term treatment of heart transplant ( HTx ) recipients indicates effects of high-intensity interval training ( HIIT ) on several parameters , including oxygen uptake , vascular function and psychological distress . In this study we compare the effect of HIIT vs continued moderate training ( CON ) on vascular function , biomarkers and health-related quality of life ( HRQoL ) in HTx recipients . METHODS A r and omized , controlled crossover trial of stable HTx recipients > 12 months after transplantation was done on patients with 12 weeks of HIIT or 12 weeks of CON , followed by a 5-month washout and crossover . Outcomes included endothelial function , arterial stiffness , biomarkers , HRQoL and markers of anxiety and depression . RESULTS Sixteen HTx recipients ( mean age 52 years , 75 % male ) completed the study . HIIT increased VO(2peak ) more than CON ( between-group difference , p < 0.001 ) . The physical component score of the 36-item Short Form ( SF-36 ) was increased significantly in HIIT patients ( p = 0.02 ) and borderline increased in CON patients ( p = 0.07 ) , whereas there was no significant effect of exercise on the mental component . Depression score decreased significantly in HIIT patients ( p = 0.04 ) with no change in CON patients ( p = 0.75 ) , whereas anxiety score decreased significantly in both HIIT ( p < 0.01 ) and CON ( p < 0.05 ) patients . There were no between-group differences in any of the measures ( all p > 0.05 ) . Arterial stiffness and biomarkers were not changed , nor did endothelial function change after HIIT ( p = 0.08 ) or CON ( p = 0.68 ) . CONCLUSIONS HIIT and CON are both well tolerated and induce similar improvements in physical components of HRQoL and in markers of anxiety . Effects of either training modality on vascular function and biomarkers could not be confirmed BACKGROUND The role of walking , as compared with vigorous exercise , in the prevention of cardiovascular disease remains controversial . Data for women who are members of minority racial or ethnic groups are particularly sparse . METHODS We prospect ively examined the total physical-activity score , walking , vigorous exercise , and hours spent sitting as predictors of the incidence of coronary events and total cardiovascular events among 73,743 postmenopausal women 50 to 79 years of age in the Women 's Health Initiative Observational Study . At base line , participants were free of diagnosed cardiovascular disease and cancer , and all participants completed detailed question naires about physical activity . We documented 345 newly diagnosed cases of coronary heart disease and 1551 total cardiovascular events . RESULTS An increasing physical-activity score had a strong , grade d , inverse association with the risk of both coronary events and total cardiovascular events . There were similar findings among white women and black women . Women in increasing quintiles of energy expenditure measured in metabolic equivalents ( the MET score ) had age-adjusted relative risks of coronary events of 1.00 , 0.73 , 0.69 , 0.68 , and 0.47 , respectively ( P for trend , < 0.001 ) . In multivariate analyses , the inverse gradient between the total MET score and the risk of cardiovascular events remained strong ( adjusted relative risks for increasing quintiles , 1.00 , 0.89 , 0.81 , 0.78 , and 0.72 , respectively ; P for trend < 0.001 ) . Walking and vigorous exercise were associated with similar risk reductions , and the results did not vary substantially according to race , age , or body-mass index . A brisker walking pace and fewer hours spent sitting daily also predicted lower risk . CONCLUSIONS These prospect i ve data indicate that both walking and vigorous exercise are associated with substantial reductions in the incidence of cardiovascular events among postmenopausal women , irrespective of race or ethnic group , age , and body-mass index . Prolonged sitting predicts increased cardiovascular risk UNLABELLED In heart transplant patients it is common to observe a reduced exercise capacity and diminished quality of life . The objective of this study was to compare the effectiveness of a hospital-based exercise program versus that of a home-based exercise program on the functional capacity , quality of life , and psychological symptoms among heart transplant patients . METHODS Thirty-eight heart transplant patients were r and omly placed into two groups : a hospital-based exercise program ( group 1 , n = 15 ) or a home-based exercise program ( group 2 , n = 13 ) . All patients performed flexibility , stretching , aerobic , strengthening , breathing , and relaxation exercise programs for 8 weeks . We performed estimates of functional capacity ( maximal oxygen consumption-pVO2 ) , quality of life ( Short Form-36-SF36 ) , and psychological symptoms ( Beck Depression Inventory-BDI , the State-Trait Anxiety Inventory-STAI ) . RESULTS In group 1 , significant increases were observed in pVO2 and all SF36 subgroups , with the exception of vitality and social function subgroups ( P < .05 ) . Significant increases were not observed on the BDI or STAI ( P > .05 ) . Group 2 failed to show significant improvements in any variable , with the exception of the score on the bodily pain subgroup of the SF36 ( P > .05 ) . CONCLUSION Based on our clinical results , we recommend a well-organized exercise program performed in a rehabilitation unit to improve postoperative exercise capacity and quality of life among heart transplant patients BACKGROUND Cardiac allograft vasculopathy ( CAV ) is a progressive form of atherosclerosis occurring in heart transplant ( HTx ) recipients , leading to increased morbidity and mortality . Given the atheroprotective effect of exercise on traditional atherosclerosis , we hypothesized that high-intensity interval training ( HIIT ) would reduce the progression of CAV among HTx recipients . METHODS Forty-three cardiac allograft recipients ( mean ± SD age 51 ± 16 years ; 67 % men ; time post-HTx 4.0 ± 2.2 years ) , all clinical ly stable and > 18 years old , were r and omized to either a HIIT group or control group ( st and ard care ) for 1 year . The effect of training on CAV progression was assessed by intravascular ultrasound ( IVUS ) . RESULTS IVUS analysis revealed a significantly smaller mean increase [ 95 % CI ] in atheroma volume ( PAV ) of 0.9 % [ 95 % CI -;0.3 % to 1.9 % ] in the HIIT group as compared with the control group , 2.5 % [ 1.6 % to 3.5 % ] ( p = 0.021 ) . Similarly , the mean increase in total atheroma volume ( TAV ) was 0.3 [ 0.0 to 0.6 ] mm(3)/mm in the HIT group vs 1.1 [ 0.6 to 1.7 ] mm(3)/mm in the control group ( p = 0.020 ) , and mean increase in maximal intimal thickness ( MIT ) was 0.02 - 0.01 to 0.04 ] mm in the HIIT group vs 0.05 [ 0.03 to 0.08 ] mm in the control group ( p = 0.054 ) . Qualitative plaque progression ( virtual histology parameters ) and inflammatory activity ( biomarkers ) were similar between the 2 groups during the study period . CONCLUSIONS HIIT among maintenance HTx recipients result ed in a significantly impaired rate of CAV progression . Future larger studies should address whether exercise rehabilitation strategies should be included in CAV management protocol Exercise training is an effective intervention for treating and preventing hypertension , but its effects on heart rate ( HR ) response to exercise and cardiorespiratory fitness ( CRF ) of non-hypertensive offspring of hypertensive parents ( FH+ ) has not been studied . We compared the effects of three times per week equal-volume high-intensity aerobic interval ( AIT ) and continuous moderate-intensity exercise ( CME ) on HR response to exercise and CRF of FH+ . Forty-four young FH+ women ( 25.0 ± 4.4 years ) r and omized to control ( CON ; n = 12 ) , AIT ( 80–90 % of VO2MAX ; n = 16 ) , or CME ( 50–60 % of VO2MAX ; n = 16 ) performed a grade d exercise test ( GXT ) before and after 16 weeks of follow-up to evaluate HR response to exercise and several parameters of CRF . Resting , maximal , and reserve HR did not change after the follow-up in all groups . HR recovery ( difference between HRMAX and HR at 1 minute of GXT recovery phase ) improved only after AIT ( 11.8 ± 4.9 vs. 20.6 ± 5.8 bpm , p < 0.01 ) . Both exercise programmes were effective for improving CRF parameters , but AIT was more effective than CME for improving oxygen consumption at the respiratory compensation point ( VO2RCP ; 22.1 % vs. 8.8 % , p = 0.008 ) and maximal effort ( VO2MAX ; 15.8 % vs. 8.0 % , p = 0.036 ) , as well as tolerance time ( TT ) to reach anaerobic threshold ( TTAT ; 62.0 vs. 37.7 , p = 0.048 ) , TTRCP ( 49.3 vs. 32.9 , p = 0.032 ) , and TTMAX ( 38.9 vs. 29.2 , p = 0.042 ) . Exercise intensity was an important factor in improving HR recovery and CRF of FH+women . These findings may have important implication s for design ing exercise-training programmes for the prevention of an inherited hypertensive disorder BACKGROUND In patients who have received a cardiac transplant , the denervated donor heart responds abnormally to exercise and exercise tolerance is reduced . The role of physical exercise in the treatment of patients who have undergone cardiac transplantation has not been determined . We assessed the effects of training on the capacity for exercise early after cardiac transplantation . METHODS Twenty-seven patients who were discharged within two weeks after receiving a heart transplant were r and omly assigned to participate in a six-month structured cardiac-rehabilitation program ( exercise group , 14 patients ) or to undergo unstructured therapy at home ( control group , 13 patients ) . Each patient in the exercise group underwent an individualized program of muscular-strength and aerobic training under the guidance of a physical therapist , whereas control patients received no formal exercise training . Cardiopulmonary stress testing was performed at base line ( within one month after heart transplantation ) and six months later . RESULTS As compared with the control group , the exercise group had significantly greater increases in peak oxygen consumption ( mean increase , 4.4 ml per kilogram of body weight per minute [ 49 percent ] vs. 1.9 ml per kilogram per minute [ 18 percent ] ; P=0.01 ) and workload ( mean increase , 35 W [ 59 percent ] vs. 12 W [ 18 percent ] ; P=0.01 ) and a greater reduction in the ventilatory equivalent for carbon dioxide ( mean decrease , 13 [ 20 percent ] vs. 6 [ 11 percent ] ; P=0.02 ) . The mean dose of prednisone , the number of patients taking antihypertensive medications , the average number of episodes of rejection and of infection during the study period , and weight gain did not differ significantly between the groups . CONCLUSIONS When initiated early after cardiac transplantation , exercise training increases the capacity for physical work This study examined the effect of 12 weeks of combined aerobic and resistance training on aerobic capacity , left ventricular ejection fraction , and arterial afterload during submaximal cycle exercise in 18 recent ( < 1 month from transplantation ) cardiac transplant recipients . The main finding of this study is that 12 weeks of combined aerobic and resistance training is an effective intervention to increase aerobic capacity in this population . However , exercise training was not associated with favorable improvements in left ventricular systolic function , because stroke volume and ejection fraction were reduced after training because of an increase in arterial afterload Abstract Objectives . This study investigates the effect of aerobic interval training on diastolic function at rest and during exercise in stable heart transplant ( HTx ) recipients . Design . Twenty-three stable HTx recipients ( 74 % males , mean age 50 ± 14.9 years ) were recruited to a training programme . Intervention was 8 weeks intensive training or control in a r and omized controlled design . Results . At baseline , participants had normal or mild diastolic dysfunction at rest . During exercise , mean E/e′ increased from 9.0 ( ± 2.8 ) to 12.8 ( ± 7.7 ) ( p = 0.09 ) , E/A increased from 2.1 ( ± 0.6 ) to 2.6 ( ± 0.7 ) ( p = 0.02 ) , and deceleration time decreased by over 50 ms , all markers of increased filling pressure . There were no correlations between diastolic function and VO2peak at baseline . After intervention VO2peak increased from 23.9 ( ± 4.5 ) to 28.3(± 6 ) ml/kg/min in the training group ( difference between groups p = 0.0018 ) . No consistent pattern of improvement in diastolic function at rest or during exercise was seen . Conclusion . The study does not support a role of diastolic dysfunction in the limited exercise capacity of HTx recipients and suggests that in these patients peripheral factors are of greater importance The purpose of this study was to determine the efficacy of resistance exercise in reversing skeletal muscle myopathy in heart transplant recipients . Myopathy , engendered by both heart failure and immunosuppression with glucocorticoids , is a post-transplant complication . The sequelae of myopathic disease includes fiber-type shifts and deficits in aerobic metabolic capability . We r and omly assigned patients to either 6 months of resistance exercise ( training group ; n = 8) or a control ( control group ; n = 7 ) group . Exercise was initiated at 2 months after transplant . Biopsy of the right vastus lateralis was performed before and after the 6-month intervention . Myosin heavy chain ( MHC ) composition was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis . Biochemical assays were performed to determine citrate synthase , 3-hydroxyacyl-CoA-dehydrogenase , and lactate dehydrogenase activity . There were no group differences ( p > or=0.05 ) in MHC composition and enzymatic reserve at baseline . Improvements in the training group for citrate cynthase ( + 40 % ) , 3-hydroxyacyl-CoA-dehydrogenase ( + 10 % ) , and lactate dehydrogenase activity ( + 48 % ) were significantly greater ( p < or=0.05 ) than in the control group ( + 10 % , -15 % , and + 20 % , respectively ) . Oxidative type 1 MHC isoform concentration increased significantly in the training group ( + 73 % , p < or=0.05 ) but decreased in the control group ( -28 % ; p < or=0.05 ) . Glycolytic type 2x MHC isoform increased significantly ( 17 % ; p < or=0.05 ) in the control group but decreased ( -33 % ; p < or=0.05 ) in the training group . This is the first study to demonstrate that resistance training elicits myofibrillar shifts from less oxidative type II fibers to more oxidative fatigue-resistant type I fibers in heart transplant recipients . Resistance exercise initiated early in the post-transplant period is efficacious in changing skeletal muscle phenotype through increases in enzymatic reserve and shifts in fiber morphology Background Heart transplant recipients have lower exercise capacity and impaired cardiac function compared with the normal population . High-intensity interval training ( HIIT ) improves exercise capacity and cardiac function in patients with heart failure and hypertension , but the effect on cardiac function in stable heart transplant recipients is not known . Thus , we investigated whether HIIT improved cardiac function and exercise capacity in stable heart transplant recipients by use of comprehensive rest- and exercise-echocardiography and cardiopulmonary exercise testing . Design and methods Fifty-two clinical ly stable heart transplant recipients were r and omised either to HIIT ( 4 × 4 minutes at 85–95 % of peak heart rate three times per week for eight weeks ) or to control . Three such eight-week periods were distributed throughout one year . Echocardiography ( rest and submaximal exercise ) and cardiopulmonary exercise testing were performed at baseline and follow-up . Results One year of HIIT increased VO2peak from 27.7 ± 5.5 at baseline to 30.9 ± 5.0 ml/kg/min at follow-up , while the control group remained unchanged ( 28.5 ± 7.0 vs. 28.0 ± 6.7 ml/kg per min , p < 0.001 for difference between the groups ) . Systolic and diastolic left ventricular functions at rest and during exercise were generally unchanged by HIIT . Conclusions Whereas HIIT is feasible in heart transplant recipients and effectively improves exercise capacity , it does not alter cardiac systolic and diastolic function significantly . Thus , the observed augmentation in exercise capacity is best explained by extra-cardiac adaptive mechanisms BACKGROUND A recommended component of heart transplant recipients ( HTR ) is endurance-oriented exercise therapy . However , the trainability of HTR after transplantation is vague . We examined the effect of high-volume and -intensity exercise training on exercise performance in HTR , compared with HTR undergoing regular rehabilitation training , and sedentary healthy subjects ( SHS ) . METHODS We studied four groups of individuals ; of those , three groups were HTR . Subjects were a regularly trained HTR group of denervated ( HTR-D ; N = 15 ) , reinnervated ( HTR-R ; N = 26 ) hearts , a high-volume and -intensity endurance-training group ( training time 7 - 20 h.wk(-1 ) ; HTR-ET ; N = 12 ) , and a group of sedentary healthy subjects ( SHS ; N = 21 ) . All participants performed cardiopulmonary exercise testing . RESULTS The HTR-ET achieved a significantly higher performance ( 255 + /- 47 W , VO(2max ) of 45.2 + /- 6.9 mL.kg(-1).min(-1 ) ) in contrast to all other groups ( HTR-D : 119 + /- 17 W , VO(2max ) of 17.4 + /- 4.5 mL.kg(-1).min(-1 ) ; HTR-R : 119 + /- 17 W , VO(2max ) of 16.9 + /- 3.7 mL.kg(-1).min(-1 ) ; SHS : 184 + /- 19 W , VO(2max ) of 35.0 + /- 6.9 mL.kg(-1).min(-1 ) ) . The HR at maximal power output in the HTR-ET was 169 + /- 17 bpm and similar to SHS ( 164 + /- 17 bpm ) , but significantly higher than HTR-D ( 125 + /- 16 ) and HTR-R ( 142 + /- 10 ) . Maximal lactate concentration ( LAmax ) of HTR-ET was 9.9 + /- 2.2 mmol . L(-1 ) , comparable to SHS ( 9.2 + /- 2.1 mmol . L(-1 ) ) , and significantly higher than HTR-D ( 5.5 + /- 1.5 mmol . L(-1 ) ) and HTR-R ( 5.1 + /- 1.0 mmol . L(-1 ) ) . CONCLUSIONS Data suggest that HTR can perform high-volume and -intensity exercise training , reaching exercise performance comparable to or even exceeding values of sedentary or moderately trained healthy subjects BACKGROUND Exercise performance in heart-transplanted patients increases with respect to pre-transplantation but remains subnormal , and it does not improve with time after surgery . Possible causes include persisting denervation , and sympathetic vasoconstriction inducing functional vascular abnormalities that prevent adequate increase in blood flow to the exercising limbs . We tested the effects of physical training on baroreceptors-mediated control of heart rate and blood pressure in recently heart-transplanted subjects . METHODS Patients were r and omly allocated to physical training ( n=13 , 30 min cycling at 60 - 70 % of peak oxygen consumption for 5 days/week for 6 months ) or to control ( n=11 ) . Upright exercise test to exhaustion was performed at the beginning of the study after 3 and 6 months . Reflex changes in RR interval and blood pressure in response to sinusoidal neck suction ( 6 and 12 cycles/min 0 to -30 mm Hg swing ) were considered as evidence of reinnervation and baroreflex control of blood pressure , respectively . RESULTS After 6 months peak oxygen consumption ( p<0.001 ) , exercise time ( p<0.01 ) and workload ( p<0.01 ) increased in trained patients . Before training RR interval and blood pressure were not modified by neck suction . After physical training systolic ( p<0.01 ) and diastolic blood pressure decreased , RR interval and blood pressure could be modulated ( p<0.05 ) by slow ( 6 cycles/min ) neck suction , indicating initial cardiac sympathetic reinnervation and restored sensitivity to autonomic modulation on the arteries . No changes were observed in controls . CONCLUSIONS Physical training improved exercise performance and the control exerted by the autonomic nervous system through the sympathetic nerves at both cardiac and vascular level The aim of this study was to examine the effects of 12 weeks of supervised aerobic and strength training ( SET ) versus no‐training ( NT ) on peak aerobic power ( VO2peak ) , submaximal exercise left ventricular ( LV ) systolic function , peripheral vascular function , lean tissue mass and maximal strength in clinical ly stable heart transplant recipients ( HTR ) . Forty‐three HTR were r and omly assigned to 12 weeks of SET ( n = 22 ; age : 57 ± 10 years ; time posttransplant : 5.4 ± 4.9 years ) or NT ( n = 21 ; age : 59 ± 11 years ; time posttransplant : 4.4 ± 3.3 years ) . The change in VO2peak ( 3.11 mL/kg/min , 95 % CI : 1.2–5.0 mL/kg/min ) , leg and total lean tissue mass ( 0.78 kg , 95 % CI : 0.31–1.3 kg and 1.34 kg , 95 % CI : 0.34–2.3 kg , respectively ) , chest‐press ( 10.4 kg , 95 % CI : 5.2–15.5 kg ) and leg‐press strength ( 34.7 kg , 95 % CI : 3.7–65.6 kg ) were significantly higher after SET versus NT . No significant change was found for submaximal exercise LV systolic function or brachial artery endothelial‐dependent or ‐independent vasodilation . Supervised exercise training is an effective intervention to improve VO2peak , lean tissue mass and muscle strength in HTR . This training regimen did not improve exercise LV systolic function or brachial artery endothelial function Coronary allograft vasculopathy is a well‐known long‐term complication after cardiac transplantation . Endothelial dysfunction is involved and may be prevented by aerobic exercise . The purpose of this study was to examine whether high intensity aerobic exercise improves peak oxygen uptake ( VO2 peak ) and endothelial function in heart transplant ( HT ) recipients . Twenty‐seven long‐term HT recipients were r and omized to either 8‐weeks high intensity aerobic exercise or no training . Flow mediated dilation of the brachial artery ( FMD ) was measured by ultrasound and VO2 peak by the analysis of expired air . Blood pressure and biomarkers were measured before and after 8 weeks . VO2 peak increased significantly in the exercise group ( VO2 peak 23.9 ± 1.79 to 28.3 ± 1.63 mL/kg/min compared to controls ( VO2 peak 24.6 ± 1.38 to 23.4 ± 1.58 , p < 0.001 exercise vs. control).FMD increased in the exercise group compared to controls ( 8.3 ± 1.1 % to 11.4 ± 1.2 % vs. 5.6 ± 1.0 % to 5.3 ± 1.7 % , p = 0.024 ) . No increase in nitroglycerin‐induced vasodilation was observed . Systolic blood pressure fell in the exercise group ( 142 ±4.2 mmHg to127 ± 3.4 mmHg , p = 0.01 ) and was unchanged in controls ( 141 ± 4.2 mmHg to 142 ±6.4 mmHg , NS ) . High intensity aerobic exercise reduces systolic blood pressure and improves endothelial function in HT recipients Background : A hospital-based cardiac rehabilitation program can significantly improve the cardiopulmonary endurance and quality of life ( QOL ) in patients after orthotopic heart transplantation ( OHT ) . Home-based programs for these patients have advantages of low cost and high accessibility , but little is known about their efficacy . This prospect i ve study was design ed to evaluate the effect of an 8-week home-based exercise program on muscular strength and endurance of lower limbs , aerobic capacity and QOL in OHT recipients . Methods : Thirty-seven OHT recipients were r and omized into exercise ( n = 14 ) or control ( n = 23 ) groups . Exercise group subjects were to exercise at least 3 times a week for 8 weeks . Each subject was evaluated by Cybex testing of right quadriceps strength and endurance , 1-min sit-to-st and test , a symptom-limited maximal exercise test and QOL assessment before and after 8 weeks . Results : Subjects in the exercise group improved significantly in sit-to-st and test , fatigue index of the right quadriceps , maximal workload achieved and physical domain of QOL compared to controls after 8 weeks , regardless of older age and lower value for sit-to-st and test at baseline . Conclusions : OHT recipients can significantly improve their muscular endurance , sit-to-st and test scores and QOL after a medically directed home-based exercise program |
1,603 | 30,149,418 | In vitro and animal studies have shown a potential chemopreventive effect of statins and their efficacy in adjuvant therapy of colorectal cancer .
Statins also show a potential role in chemoprevention of colorectal cancer in patients with inflammatory bowel disease .
CONCLUSIONS Accumulating evidence suggests that statins may have a role in colorectal cancer prevention and treatment . | OBJECTIVES Statins act by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase and are an important drug class in the treatment of lipid disorders .
They lower cholesterol levels and modulate cardiovascular disease risk in both primary and secondary prevention .
In addition , some studies have shown that statins may have an effect on colorectal cancer development and treatment .
Our objective is to summarize published studies on the effect of statins on colorectal carcinogenesis . | Numerous r and omized , double-blind , placebo-controlled studies and observational studies have shown that statins reduce mortality and major cardiovascular events in older high-risk persons with hypercholesterolemia . The Heart Protection Study showed that statins reduced mortality and major cardiovascular events in high-risk persons regardless of the initial level of serum lipids , age , or gender . The up date d National Cholesterol Education Program III guidelines state that in very high-risk persons , a serum low-density lipoprotein ( LDL ) cholesterol level of < 70 mg/dl ( 1.8 mmol/l ) is a reasonable clinical strategy for moderately high-risk persons ( 2 or more risk factors and a 10-year risk for coronary artery disease of 10 % to 20 % ) , and the serum LDL cholesterol should be reduced to < 100 mg/dl ( 2.6 mmol/l ) . When LDL cholesterol-lowering drug therapy is used to treat high-risk persons or moderately high-risk persons , the serum LDL cholesterol should be reduced by at least 30 % to 40 % . The serum LDL cholesterol should be decreased to less than 160 mg/dl in persons at low risk for cardiovascular disease . Addition of other lipid-lowering drugs to statin therapy has not been demonstrated to further reduce cardiovascular events and mortality Summary Purpose Pre clinical data has demonstrated the potential of simvastatin to overcome cetuximab resistance in KRAS mutant CRC patients . Therefore , we design ed a study using simvastatin/cetuximab/irinotecan for KRAS mutant CRC patients who are refractory to irinotecan and oxaliplatin-based chemotherapy . Patients and methods In this phase II study , patients received 500 mg/m2 cetuximab , 150–180 mg/m2 ( day 1 ) , and 80 mg simvastatin ( once daily , days 1–14 , every 2 weeks ) . The primary endpoint was the objective response rate ( ORR ) . Secondary endpoints were progression-free survival ( PFS ) , overall survival ( OS ) , the disease control rate ( DCR ) , and safety . We also analyzed the relationship between the RAS gene expression signature score and treatment response to simvastatin/cetuximab/irinotecan . Results Fifty-two KRAS mutant CRC patients were enrolled . The ORR ( complete response [ CR ] , 0 ; partial response [ PR ] , 1 ) was 1.9 % ( 95 % confidence interval [ CI ] , −1.8–5.6 ) . The DCR ( CR , 0 ; PR , 1 ; stable disease , 33 ) was 65.4 % ( 95 % CI , 52.5–78.3 ) . The median PFS and OS from the time of study drug administration were 7·6 months ( 95 % CI , 4.4–10.8 ) and 12.8 months ( 95 % CI , 9.5–16.2 ) , respectively . The most common grade 3/4 adverse events were anemia ( 28.8 % ) , neutropenia ( 13.5 % ) , and diarrhea ( 7.7 % ) . The RAS signature score was significantly correlated with the maximal change in target lesions from baseline ( r = 0.57 , P = 0.014 ) . Conclusion The simvastatin/cetuximab/irinotecan regimen showed promising efficacy and safety in KRAS mutant CRC patients who failed irinotecan and oxaliplatin-based chemotherapy . The RAS signature may be a novel predictor of treatment response to cetuximab-combined chemotherapy in CRC patients Importance Patients with cancer who use statins appear to have a substantially better survival than nonusers in observational studies . However , this inverse association between statin use and mortality may be due to selection bias and immortal-time bias . Objective To emulate a r and omized trial of statin therapy initiation that is free of selection bias and immortal-time bias . Design , Setting , and Participants We used observational data on 17 372 patients with cancer from the Surveillance , Epidemiology , and End Results (SEER)-Medicare data base ( 2007 - 2009 ) with complete follow-up until 2011 . The SEER-Medicare data base links 17 US cancer registries and cl aims files from Medicare and Medicaid in 12 US states . We included individuals with a new diagnosis of colorectal , breast , prostate , or bladder cancer who had not been prescribed statins for at least 6 months before the cancer diagnosis . Individuals were duplicated , and each replicate was assigned to either the strategy “ statin therapy initiation within 6 months after diagnosis ” or “ no statin therapy initiation . ” Replicates were censored when they stopped following their assigned strategy , and the potential selection bias was adjusted for via inverse-probability weighting . Hazard ratios ( HRs ) , cumulative incidences , and risk differences were calculated for all-cause mortality and cancer-specific mortality . We then compared our estimates with those obtained using the same analytic approaches used in previous observational studies . Exposures Statin therapy initiation within 6 months after cancer diagnosis . Main Outcomes and Measures Cancer-specific and all-cause mortality using SEER-Medicare data and data from previous studies . Results Of the 17 372 patients whose data were analyzed , 8440 ( 49 % ) were men , and 8932 ( 51 % ) were women ( mean [ SD ] age , 76.4 [ 7.4 ] years ; range , 66 - 115 years ) . The adjusted HR ( 95 % CI ) comparing statin therapy initiation vs no initiation was 1.00 ( 0.88 - 1.15 ) for cancer-specific mortality and 1.07 ( 0.93 - 1.21 ) for overall mortality . Cumulative incidence curves for both groups were almost overlapping ( the risk difference never exceeded 0.8 % ) . In contrast , the methods used by prior studies result ed in an inverse association between statin use and mortality ( pooled hazard ratio 0.69 ) . Conclusion and Relevance After using methods that are not susceptible to selection bias from prevalent users and to immortal time bias , we found that initiation of therapy with statins within 6 months after cancer diagnosis did not appear to improve 3-year cancer-specific or overall survival BACKGROUND & AIMS Statin use has been associated with a reduced incidence of colorectal cancer and might also affect survival of patients diagnosed with colon cancer . Statins are believed to inhibit Ras signaling and may also activate the bone morphogenetic protein ( BMP ) signaling pathway in colorectal cancer cells . We investigated the effects of statins on overall survival of patients with a diagnosis of colon cancer , and whether their effects were associated with changes in KRAS or the BMP signaling pathways . METHODS Data were derived from the PHARMO data base network ( Netherl and s ) and linked to patients diagnosed with colon cancer from 2002 through 2007 , listed in the Eindhoven Cancer Registry . We obtained information on causes of death from statistics Netherl and s. We constructed a tissue microarray of 999 colon cancer specimens from patients who underwent surgical resection from 2002 through 2008 . Survival was analyzed with statin user status after diagnosis as a time-dependent covariate . Multivariable Poisson regression survival models and Cox analyses were used to study the effect of statins on survival . Tumor tissues were analyzed by immunohistochemistry for levels of SMAD4 , BMPR1A , BMPR1B , and BMPR2 proteins . Tumor tissues were considered to have intact BMP signaling if they contained SMAD4 plus BMPR1A , BMPR1B , or BMPR2 . DNA was isolated from tumor tissues and analyzed by quantitative polymerase chain reaction to detect mutations in KRAS . The primary outcome measures were overall mortality and cancer-specific mortality . RESULTS In this cohort , 21.0 % of the patients ( 210/999 ) were defined as statin users after diagnosis of colon cancer . Statin use after diagnosis was significantly associated with reduced risk of death from any cause ( adjusted relative risk [ RR ] , 0.67 ; 95 % confidence interval [ CI ] , 0.51 - 0.87 ; P = .003 ) and death from cancer ( adjusted RR , 0.66 ; 95 % CI , 0.49 - 0.89 ; P = .007 ) . Statin use after diagnosis was associated with reduced risk of death from any cause or from cancer for patients whose tumors had intact BMP signaling ( adjusted RR , 0.39 ; 95 % CI , 0.22 - 0.68 ; P = .001 ) , but not for patients whose tumors did not have BMP signaling ( adjusted RR , 0.81 ; 95 % CI , 0.55 - 1.21 ; P = .106 ; P < .0001 for the interaction ) . Statin use after diagnosis was not associated with reduced risk of death from any cause or from cancer for patients whose tumors did not contain KRAS mutations ( adjusted RR , 0.81 ; 95 % CI , 0.56 - 1.18 ; P = .273 ) or whose tumors did have KRAS mutations ( adjusted RR , 0.59 ; 95 % CI 0.35 - 1.03 ; P = .062 ; P = .90 for the interaction ) . CONCLUSIONS In an analysis of 999 patients with a diagnosis of colon cancer , we associated statin with reduced risk of death from any cause or from cancer . The benefit of statin use is greater for patients whose tumors have intact BMP signaling , independent of KRAS mutation status . R and omized controlled trials are required to confirm these results BACKGROUND Atorvastatin , rosuvastatin and pitavastatin are available for intensive , aggressive low-density lipoprotein cholesterol (LDL-C)-lowering therapy in clinical practice . The objective of the R and omized Head-to-Head Comparison of Pitavastatin , Atorvastatin , and Rosuvastatin for Safety and Efficacy ( Quantity and Quality of LDL ) ( PATROL ) Trial was to compare the safety and efficacy of atorvastatin , rosuvastatin and pitavastatin head to head in patients with hypercholesterolemia . This is the first prospect i ve r and omized multi-center trial to compare these strong statins ( UMIN Registration No : 000000586 ) . METHODS AND RESULTS Patients with risk factors for coronary artery disease and elevated LDL-C levels were r and omized to receive atorvastatin ( 10mg/day ) , rosuvastatin ( 2.5mg/day ) , or pitavastatin ( 2mg/day ) for 16 weeks . Safety was assessed in terms of adverse event rates , including abnormal clinical laboratory variables related to liver and kidney function and skeletal muscle . Efficacy was assessed by the changes in the levels and patterns of lipoproteins . Three hundred and two patients ( from 51 centers ) were enrolled , and these 3 strong statins equally reduced LDL-C and LDL particles , as well as fast-migrating LDL ( modified LDL ) by 40 - 45 % . Newly developed pitavastatin was non-inferior to the other 2 statins in lowering LDL-C. There were no differences in the rate of adverse drug reactions among the 3 groups , but HbA(1c ) was increased while uric acid was decreased in the atorvastatin and rosuvastatin groups . CONCLUSIONS The safety and efficacy of these 3 strong statins are equal . It is suggested that the use of these 3 statins be completely dependent on physician discretion based on patient background BACKGROUND Several studies have indicated that statins may have anticarcinogenic effects . The aim of the present study was to investigate if statin treatment was associated with a reduced risk of hepatocellular carcinoma ( HCC ) or colon cancer . METHODS A nationwide case-control study was carried out in which all cases of HCC and colon cancer in the Swedish population above 40 years of age between 1 July 2006 and 31 December 2010 were identified in the Swedish Cancer Register . For every case , five controls were selected and matched on age and sex . Data on statin use was extracted from the Swedish Prescribed Drug Register . We estimated risks using conditional logistic regression and adjusted for educational level , concomitant medications and comorbidity . RESULTS Identified were 3994 cases of HCC and matched with 19.970 controls , and 21.143 cases of colon cancer were identified and matched with 105.715 controls . In the adjusted analysis , the odds ratio ( OR ) for HCC among statin users was 0.88 ( 95 % confidence interval ( CI ) 0.81 - 0.96 ) , and the OR for colon cancer was 1.04 ( 95%CI 1.00 - 1.08 ) compared with non-users . CONCLUSION Statin use was associated with a modest decreased risk of HCC but did not influence the risk of colon cancer . Future r and omized placebo-controlled trials in HCC high-risk patients are warranted to further investigate the possible prophylactic effect of statins in HCC Pre clinical data showed anticancer effects of statins in melanoma , but meta‐analyses could not demonstrate a reduced melanoma incidence in statin users . Rather than preventing occurrence , statins might reduce growth and metastatic spread of melanomas and ultimately improve survival . In this population ‐based study , we investigated the relationship between statin use and survival of melanoma patients . Patients ≥18 years who were diagnosed with cutaneous melanoma ( Breslow thickness > 1 mm ) and registered in the Eindhoven Cancer Registry and in PHARMO Data base Network between 1 January 1998 and 31 December 2010 were eligible . The hazard ratio ( HR ) of all‐cause mortality was calculated by employing adjusted time‐dependent and time‐fixed Cox proportional hazard models . Disease‐specific survival was estimated by means of 3‐year relative survival rates ( RSR ) . A control cohort of r and omly selected patients using statins from PHARMO Data base Network matched on age and gender was used to compare RSR of statin users to the general population . After melanoma diagnosis , 171 of 709 patients used statins . Use of statins showed a nonsignificantly decreased hazard of death ( adjusted HR 0.76 , 95 % confidence interval [ CI ] 0.50–1.61 ) . After stratification for gender , male but not female statin users showed a favorable outcome compared to nonusers ( HR 0.57 , 95 % CI 0.32–0.99 ; HR 1.22 , 95 % CI 0.62–2.38 , respectively ) . Three‐year RSR for male statin users tended to be higher than for nonusers ( 91 % vs. 80.5 % , P = 0.06 ) , no differences were observed in women ( 87.1 % vs. 92.5 % , P = 0.76 ) . Statin use was not associated with an improved survival of melanoma patients . The trend for better survival of male in contrast to female statin users warrants further research Background : There is increasing evidence that aspirin , statins and ACE-inhibitors can reduce the incidence of colorectal cancer . The aim of the present study was to assess the impact of these medications on an individual ’s risk of advanced neoplasia in a colorectal cancer screening programme . Methods : A prospect ively maintained data base of the first round of screening in our geographical area was analysed . The outcome measure was advanced neoplasia ( cancer or intermediate or high risk adenomata ) . Results : Of the 4188 individuals who underwent colonoscopy following a positive occult blood stool test , colorectal pathology was present in 3043(73 % ) . Of the 3043 patients with colorectal pathology , 1704(56 % ) had advanced neoplasia . Patients with advanced neoplasia were more likely to be older ( OR 1.38 ; 95 % CI 1.19–1.59 ) and male ( OR 1.66 ; 95 % CI 1.43–1.94 ) ( both P<0.001 ) . In contrast , those on aspirin ( OR 0.68 ; 95 % CI 0.56–0.83 ) , statins ( OR 0.65 ; 95 % CI 0.55–0.78 ) or ACE inhibitors ( OR 0.71 ; 95 % CI 0.57–0.89 ) were less likely to have advanced neoplasia at colonoscopy ( all P<0.05 ) . Conclusion : In patients undergoing colonoscopy following a positive occult blood stool test with documented evidence of aspirin , statin or ACE-inhibitor usage , advanced neoplasia is less likely , suggesting that the usage of these medications may have a chemopreventative effect BACKGROUND & AIMS Inflammatory bowel diseases ( IBDs ) such as Crohn 's disease and ulcerative colitis are associated with an increased risk of colorectal cancer ( CRC ) . Chemopreventive strategies have produced weak or inconsistent results . Statins have been associated inversely with sporadic CRC . We examined their role as chemopreventive agents in patients with IBD . METHODS We collected data from 11,001 patients with IBD receiving care at hospitals in the Greater Boston metropolitan area from 1998 through 2010 . Diagnoses of CRC were determined using vali date d International Classification of Diseases , 9th revision , Clinical Modification codes . Statin use before diagnosis was assessed through analysis of electronic prescriptions . We performed multivariate logistic regression analyses , adjusting for potential confounders including primary sclerosing cholangitis , smoking , increased levels of inflammation markers , and CRC screening practice s to identify an independent association between statin use and CRC . We performed sensitivity analyses using propensity score adjustment and variation in the definition of statin use . RESULTS In our cohort , 1376 of the patients ( 12.5 % ) received 1 or more prescriptions for a statin . Patients using statins were more likely to be older , male , white , smokers , and have greater comorbidity than nonusers . Over a follow-up period of 9 years , 2 % of statin users developed CRC compared with 3 % of nonusers ( age-adjusted odds ratio , 0.35 ; 95 % confidence interval , 0.24 - 0.53 ) . On multivariate analysis , statin use remained independently and inversely associated with CRC ( odds ratio , 0.42 ; 95 % confidence interval , 0.28 - 0.62 ) . Our findings were robust on a variety of sensitivity and subgroup analyses . CONCLUSIONS Statin use was associated inversely with the risk of CRC in a large IBD cohort . Prospect i ve studies on the role of statins as chemopreventive agents are warranted Sulindac , atorvastatin , or prebiotic dietary fiber may reduce colorectal cancer ( CRC ) risk . However , clinical trial data are currently limited . We conducted a r and omized , phase II chemoprevention trial involving subjects 40 years or older , with previously resected colon cancer or multiple/advanced colorectal adenomas . Magnification chromoendoscopy ( MCE ) was performed to identify and characterize rectal aberrant crypt foci ( ACF ) ; eligibility criteria required five or more rectal ACFs at baseline . Intervention assignments were as follows : ( a ) atorvastatin 20 mg qd ; ( b ) sulindac 150 mg bid ; ( c ) oligofructose-enriched inulin ( as ORAFTI ® Synergy1 ) 6 gm bid ; or ( d ) control ( maltodextrin ) 6 gm bid , for 6 months . Percent change in rectal ACF number ( % ΔACF ) within arm was the primary endpoint . Secondary endpoints included changes in proliferation ( Ki67 ) and apoptosis ( caspase-3 ) , as measured from normal mucosa biopsy sample s. Among 85 eligible r and omized subjects , 76 ( 86 % ) completed the trial per protocol . The median ( range ) of rectal ACF was 9 ( 5–34 ) and 8 ( 0–37 ) at baseline and postintervention , respectively . The median ( SD ) for % ΔACF was 5.6 ( −69 % to 143 % ) , −18.6 ( −83 % to 160 % ) , −3.6 ( −88 % to 83 % ) , and −10.0 ( −100 % to 117 % ) in the atorvastatin , sulindac , ORAFTI ® Synergy1 and control arms , respectively . Neither within-arm ( P = 0.12–0.59 ) nor between-arm ( P = 0.30–0.92 ) comparisons of % ΔACF were statistically significant . The active and control interventions also seemed to have similar effects on mucosal proliferation and apoptosis ( P > 0.05 for each comparison ) . Data from this multicenter , phase II trial do not provide convincing evidence of CRC risk reduction from 6-month interventions with atorvastatin , sulindac , or ORAFTI ® Synergy1 , although statistical power was limited by the relatively small sample size . Cancer Prev Res ; 4(2 ) ; 259–69 . © 2011 AACR BACKGROUND Although pre clinical and epidemiological data suggest that statins may have antineoplastic properties , the impact of statin use on patient survival after a curative resection of stage III colon cancer is unknown . METHODS We conducted a prospect i ve observational study of 842 patients with stage III colon cancer enrolled in a r and omized adjuvant chemotherapy trial from April 1999 to May 2001 to investigate the relationship between statin use and survival . Disease-free survival ( DFS ) , recurrence-free survival ( RFS ) , and overall survival ( OS ) were investigated by Kaplan-Meier curves and log-rank tests in the overall study population and in a subset of patients stratified by KRAS mutation status ( n = 394 ) , and Cox proportional hazards regression was used to assess the simultaneous impact of confounding variables . All statistical tests were two-sided . RESULTS Among 842 patients , 134 ( 15.9 % ) reported statin use after completing adjuvant chemotherapy . DFS among statin users and nonusers was similar ( hazard ratio [ HR ] of cancer recurrence or death = 1.04 , 95 % confidence interval [ CI ] = 0.73 to 1.49 ) . RFS and OS were also similar between statin users and nonusers ( adjusted HR of cancer recurrence = 1.14 , 95 % CI = 0.77 to 1.69 ; adjusted HR of death = 1.15 , 95 % CI = 0.77 to 1.71 ) . Survival outcomes were similar regardless of increasing duration of statin use before cancer diagnosis ( P(trend ) = .63 , .63 , and .59 for DFS , RFS , and OS , respectively ) . The impact of statin use did not differ by tumor KRAS mutation status , with similar DFS , RFS , and OS for statin use among mutant and wild-type subgroups ( P(interaction ) = .84 , .67 , and .98 for DFS , RFS , and OS , respectively ) . CONCLUSION Statin use during and after adjuvant chemotherapy was not associated with improved DFS , RFS , or OS in patients with stage III colon cancer , regardless of KRAS mutation status BACKGROUND : Achieving a pathologic complete response to neoadjuvant chemoradiation improves prognosis in rectal cancer . Statin therapy has been shown to enhance the impact of treatment in several malignancies , but little is known regarding the impact on rectal cancer response to neoadjuvant chemoradiation . OBJECTIVE : The purpose of this study was to determine whether statin use during neoadjuvant chemoradiation improves pathologic response in rectal cancer . DESIGN : This was a retrospective cohort study based on data from a prospect ively maintained colorectal cancer data base . The 2 cohorts were defined by statin use during neoadjuvant chemoradiation . SETTING : This study was performed at a single tertiary referral center . PATIENTS : Four hundred seven patients with primary rectal adenocarcinoma who underwent neoadjuvant therapy then proctectomy between 2000 and 2012 were included . Ninety-nine patients ( 24.3 % ) took a statin throughout the entire course of neoadjuvant therapy . MAIN OUTCOME MEASURES : The primary outcome measure was pathologic response to neoadjuvant chemoradiotherapy as defined by the American Joint Committee on Cancer tumor regression grading system , grade s 0 to 3 . RESULTS : Patients in the statin cohort had a lower median regression grade ( 1 vs 2 , p = 0.01 ) and were more likely to have a better response ( grade s 0–1 vs 2–3 ) than those not taking a statin ( 65.7 % vs 48.7 % , p = 0.004 ) . Statin use remained a significant predictor of an American Joint Committee on Cancer grade 0 to 1 ( OR , 2.25 ; 95 % CI , 1.33–3.82 ) in multivariate analyses . Although statin use itself did not significantly improve oncologic outcomes , an American Joint Committee on Cancer grade 0 to 1 response was associated with statistically significant improvements in overall survival , disease-free survival , cancer-specific mortality , and local recurrence . LIMITATIONS : This was a retrospective study and subject to nonr and omization of patients and incorporated patients on variable statin agents and doses . CONCLUSIONS : Statin therapy is associated with an improved response of rectal cancer to neoadjuvant chemoradiation . These data provide the foundation for a prospect i ve clinical trial |
1,604 | 31,653,961 | Mecapegfilgrastim , lipegfilgrastim and balugrastim might be the most appreciate G-CSF drugs with both good efficacy and tolerability when treating cancer patients after cytotoxic chemotherapy | The optimum granulocyte colony-stimulating factor ( G-CSF ) treatment for cancer patients after being treated with cytotoxic chemotherapy remains unknown . | Purpose Pegfilgrastim is a pegylated form of filgrastim , a recombinant protein of granulocyte colony-stimulating factor , that is used to reduce the risk of febrile neutropenia ( FN ) . Here , we report the results of a phase III trial of pegfilgrastim in breast cancer patients receiving docetaxel and cyclophosphamide ( TC ) chemotherapy . Methods We conducted a double-blind , placebo-controlled , r and omized trial to determine the efficacy of pegfilgrastim in reducing the risk of FN in early-stage breast cancer patients . A total of 351 women ( 177 in the pegfilgrastim group and 174 in the placebo group ) between 20 and 69 years of age with stage I – III invasive breast carcinoma who were to receive TC chemotherapy ( docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks ) as either neoadjuvant or adjuvant therapy were enrolled ; 346 of these patients were treated with either pegfilgrastim ( n = 173 ) or placebo ( n = 173 ) . Results The incidence of FN was significantly lower in the pegfilgrastim group than in the placebo group ( 1.2 vs. 68.8 % , respectively ; P < 0.001 ) . In addition , patients in the pegfilgrastim group required less hospitalization and antibiotics for FN . Most adverse events were consistent with those expected for breast cancer subjects receiving TC chemotherapy . Conclusions Pegfilgrastim is safe and significantly reduces the incidence of FN in breast cancer patients Purpose Lipegfilgrastim is a once-per-cycle , fixed-dose , glycoPEGylated recombinant granulocyte colony-stimulating factor ( G-CSF ) recently approved in Europe to reduce the duration of chemotherapy-induced neutropenia and incidence of febrile neutropenia in patients with cancer receiving chemotherapy . Bone pain-related ( BPR ) adverse events are commonly associated with G-CSF therapy . This post hoc analysis examined BPR treatment-emergent adverse events ( TEAEs ) in two comparative studies of lipegfilgrastim or pegfilgrastim in patients receiving chemotherapy . Methods A post hoc analysis was conducted using integrated data from two double-blind r and omized studies in patients with breast cancer receiving docetaxel and doxorubicin and treated prophylactically with subcutaneous lipegfilgrastim 6 mg or pegfilgrastim 6 mg once per cycle . BPR TEAEs were defined as arthralgia , back pain , bone pain , musculoskeletal chest pain , musculoskeletal discomfort , musculoskeletal pain , myalgia , neck pain , noncardiac chest pain , and pain in extremity . Relationship of BPR TEAEs to study treatment or chemotherapy was also reported by the investigators . Results The analysis included 306 patients ( lipegfilgrastim : n = 151 ; pegfilgrastim : n = 155 ) . The proportion of patients experiencing BPR TEAEs was similar with lipegfilgrastim and pegfilgrastim ( 25.2 vs 21.9 % , respectively ) , as was the proportion of patients experiencing BPR treatment-emergent adverse drug reactions ( TEADRs ) ( 18.5 vs 16.8 % , respectively ) . No BPR TEADRs were serious , and none led to discontinuation . Conclusions Nonsevere BPR TEAEs and TEADRs were observed in patients with breast cancer receiving chemotherapy and G-CSF ; rates of BPR events were similar between lipegfilgrastim and pegfilgrastim . The similar BPR safety profile of lipegfilgrastim and pegfilgrastim provides support for use in patients with breast cancer receiving chemotherapy After informed consent , 86 patients with advanced cancer undergoing potentially myelosuppressive cytotoxic chemotherapy were r and omized to receive placebo or subcutaneous granulocyte-colony stimulating factor ( G-CSF ) 5 micrograms/Kg/day in order to prevent severe neutropenia and its related morbidity . The incidence of neutropenia ( absolute neutrophil count < 1,000/mm3 ) was significantly reduced in patients receiving G-CSF than in controls ( 18 % versus 42 % ; P < 0.05 ) . The duration of neutropenia was also shortened by the administration of G-CSF ( 4.8 versus 8.2 days ; P < 0.05 ) . Therapy with G-CSF has also a positive impact on the dose-intensity of employed regimens . Patients treated with G-CSF showed oral fungal disease in 9 % of cases , while control patients had a 21 % incidence ( NS ) . Patients treated with G-CSF received 91 % of the programmed dose-intensity as compared to 71 % of control patients ( P < 0.05 ) . These data strengthen the clinical usefulness of G-CSF in the prevention of chemotherapy-related neutropenia , infections , and reduction in dose-intensity . Further studies are required to establish if the increase in dose-intensity allowed by G-CSF treatment may positively influence the outcome of cancer patients Background Patients with acute myeloid leukemia ( AML ) are often neutropenic as a result of their disease . Furthermore , these patients typically experience profound neutropenia following induction and /or consolidation chemotherapy and this may result in serious , potentially life-threatening , infection . This r and omized , double-blind , phase 2 clinical trial compared the efficacy and tolerability of pegfilgrastim with filgrastim for assisting neutrophil recovery following induction and consolidation chemotherapy for de novo AML in patients with low-to-intermediate risk cytogenetics . Methods Patients ( n = 84 ) received one or two courses of st and ard induction chemotherapy ( idarubicin + cytarabine ) , followed by one course of consolidation therapy ( high-dose cytarabine ) if complete remission was achieved . They were r and omized to receive either single-dose pegfilgrastim 6 mg or daily filgrastim 5 μg/kg , beginning 24 hours after induction and consolidation chemotherapy . Results The median time to recovery from severe neutropenia was 22.0 days for both pegfilgrastim ( n = 42 ) and filgrastim ( n = 41 ) groups during Induction 1 ( difference 0.0 days ; 95 % CI : -1.9 to 1.9 ) . During Consolidation , recovery occurred after a median of 17.0 days for pegfilgrastim versus 16.5 days for filgrastim ( difference 0.5 days ; 95 % CI : -1.1 to 2.1 ) . Therapeutic pegfilgrastim serum concentrations were maintained throughout neutropenia . Pegfilgrastim was well tolerated , with an adverse event profile similar to that of filgrastim . Conclusion These data suggest no clinical ly meaningful difference between a single dose of pegfilgrastim and multiple daily doses of filgrastim for shortening the duration of severe neutropenia following chemotherapy in de novo AML patients with low-to-intermediate risk cytogenetics . Trial registration Clinical trials.gov BACKGROUND Neutropenia is common in patients receiving myelotoxic chemotherapy . Pegfilgrastim , a sustained- duration filgrastim is a once-per-cycle therapy for prophylactic neutrophil support . PATIENTS AND METHODS Women , treated with four cycles of doxorubicin/docetaxel chemotherapy every 21 days , received pegfilgrastim or filgrastim 24 h after chemotherapy as a single subcutaneous injection per chemotherapy cycle ( pegfilgrastim 30 , 60 or 100 microg/kg ) or daily subcutaneous injections ( filgrastim 5 microg/kg/day ) . Safety , efficacy and pharmacokinetics were analyzed . RESULTS The incidence of grade 4 neutropenia in cycle 1 was 95 , 90 and 74 % , in patients who received pegfilgrastim 30 , 60 and 100 microg/kg , respectively , and 76 % in patients who received filgrastim . Mean duration of grade 4 neutropenia in cycle 1 was 2.7,2 and 1.3 days for doses of pegfilgrastim , and 1.6 days for filgrastim . The pharmacokinetics of pegfilgrastim were non-linear and dependent on both dose and neutrophil count . Pegfilgrastim serum concentration was sustained until the neutrophil nadir occurred then declined rapidly as neutrophils started to recover , consistent with a self-regulating neutrophil-mediated clearance mechanism . The safety profiles of pegfilgrastim and filgrastim were similar . CONCLUSIONS A single subcutaneous injection of pegfilgrastim 100 microg/kg provided neutrophil support and a safety profile comparable to daily subcutaneous injections of filgrastim during multiple chemotherapy cycles Sepsis associated with neutropenia remains a major cause of morbidity and mortality from many chemotherapy regimens . In a recent tabulation of commonly used chemotherapy agents [ 1 ] , 29 of 37 are listed as causing marked or moderate leukopenia . A known correlation exists between the degree and duration of neutropenia and the risk for sepsis [ 2 ] . In conjunction with neutropenia , infections with gram-negative organisms such as Pseudomonas spp . occur relatively frequently and have high morbidity and mortality rates if antibiotic therapy is not begun until infection is microbiologically confirmed [ 3 , 4 ] . Current recommended practice is to initiate empiric , broad-spectrum intravenous antibiotic therapy in all patients with febrile neutropenia at the onset of fever , despite clinical and microbiological evidence of infection being found in only 40 % to 60 % of cases [ 5 ] . In addition to antibiotic therapy , neutrophil recovery is an important factor for a successful treatment outcome in these patients [ 6 , 7 ] and has been identified as the most favorable prognostic factor in a recent multivariate logistic regression analysis of 14 variables analyzed in a study of antibiotic efficacy [ 7 ] . Granulocyte transfusions are logistically difficult , are associated with substantial toxicity , and are of uncertain efficacy [ 8 , 9 ] ; before the availability of the colony-stimulating factors , few pharmacologic agents had clinical utility in increasing neutrophil levels [ 10 ] . Filgrastim ( previously known as recombinant methionyl human granulocyte colony-stimulating factor [ r-metHuG-CSF ] ) is a hematopoietic growth factor that promotes the survival , proliferation , differentiation , and function of progenitor and mature cells of the neutrophil granulocyte lineage [ 11 ] . It has potent granulopoietic effects in vivo [ 12 - 14 ] , and its clinical pharmacology has been defined [ 15 ] . In two phase III studies [ 16 , 17 ] , filgrastim therapy that was started 1 day after chemotherapy reduced the severity and duration of neutropenia and decreased by nearly half the incidence of febrile neutropenic episodes and the average duration of hospitalization and antibiotic use per patient . The use of filgrastim to prevent febrile neutropenic episodes in patients with cancer who receive chemotherapy is now an approved indication in many countries . Not all patients with cancer who have had chemotherapy and who have been treated with filgrastim receive it to reduce the risk for neutropenic sepsis . Approximately 14 % of filgrastim in the United States has been used to treat episodes of postchemotherapy febrile neutropenia after they occur rather than to prevent them ( unpublished market research data , Amgen , Inc. ) . To determine if filgrastim administered in addition to st and ard empiric inpatient antibiotic therapy was also beneficial in patients presenting with established fever and neutropenia , we conducted a multicenter , r and omized , double-blind , placebo-controlled study . This is the first report of a study assessing therapeutic intervention with filgrastim in this clinical setting . Methods We present the analysis of findings from 218 patients enrolled at four centers between October 1988 and February 1992 . The study drug was filgrastim , a recombinant human protein produced in Escherichia coli [ 18 ] and supplied by Amgen , Inc. , Thous and Oaks , California . Patients Eligible patients with febrile neutropenia were adults ( age 16 years ) receiving chemotherapy for histologically confirmed cancer other than myeloid leukemia who had an oral temperature of greater than 38.2 C and a neutrophil count less than 1.0 109/L. The neutrophil count included the number of b and s and polymorphonuclear forms counted in manual differentials from blood smears . Patients were ineligible if they were already receiving antibiotic therapy , if they had septic shock ( a systolic blood pressure of < 90 mm Hg , poor peripheral perfusion , and abnormal mentation ) , if they were receiving myeloablative chemotherapy with marrow transplantation support , if they had severe renal impairment ( serum creatinine level > 0.7 mM ) , abnormal liver function ( bilirubin > 5 times the upper limit of normal ) , were pregnant or breast-feeding , or had a history of allergic reactions to the study antibiotics . Patients could enter the r and omized trial only once . If subsequent episodes of fever and neutropenia developed , patients were offered open-label filgrastim therapy according to the same procedures described in the protocol . Data from these episodes are not included in this report . The study was approved by the relevant institutional review boards of each treatment center , and all patients gave signed informed consent . Study Design Our study was a r and omized , double-blind , placebo-controlled trial . Patients were r and omly assigned to receive either filgrastim or placebo from identically labeled vials . Stratification was not done before r and omization . The r and omization code was maintained by the Biostatistical Department of Amgen , Inc. , and was not broken until all collected data had been verified by Amgen and its design ee , Biomedicus ( Boronia , Australia ) , and had been audited by a separate department at Amgen . Enrolled patients were admitted to the hospital , and a full medical history was taken and physical examination done . Baseline investigations included full blood counts with differential leukocyte counts and chest radiographs . Cultures of blood ( in duplicate ) , urine , and other clinical ly suspicious sites were done . Empiric treatment was started with piperacillin ( 4 g intravenously every 6 hours ) and tobramycin ( 2 mg/kg of body weight intravenously for the loading dose and 80 mg intravenously every 8 hours thereafter ) . Antibiotic dose was adjusted for patient size , renal and hepatic impairment , and drug serum levels according to st and ard criteria . Therapy with filgrastim or placebo was initiated within 12 hours of the start of antibiotic therapy at a dose of 12 g/kg per day by continuous subcutaneous infusion with the use of a portable pump . Filgrastim ( supplied in 5- or 10-mL vials as a clear , colorless solution of 300 g/mL ) or placebo ( supplied in matching vials for double-blinding ) was diluted in a sterile solution of 5 % glucose in water to a volume of 50 mL. Patients remained in the study until 4 consecutive afebrile days ( peak daily temperature , < 37.5 C ) had passed and the blood neutrophil count was greater than 0.5 109/L or until 28 days had elapsed . Filgrastim or placebo doses were reduced or the drugs were withdrawn before study completion if the blood neutrophil count exceeded 10.0 109/L ( dose reduced to 6 g/kg per day ) , 15.0 109/L ( dose reduced to 3 g/kg per day ) , or 20.0 109/L ( drug withdrawn ) . Intravenous antibiotics were administered until study completion , although the actual drugs or doses could be altered at the investigators ' discretion within broad protocol guidelines . Study End Points Our study evaluated the effect of filgrastim on the number of days of fever and on the number of days of neutropenia associated with presumed or documented infection that was treated with antibiotics . Blood counts were done daily , and oral temperatures were recorded at least four times per day . Two end points were defined for days of neutropenia and are specified here as the number of days on which the neutrophil count was less than 0.5 109/L and less than 1.0 109/L. The days of fever end point was defined as the number of consecutive days ( after and including the day of presentation ) on which the maximum oral temperature was 37.5 C or greater , plus any subsequent periods beginning with a day of temperature peak of greater than 38.2 C and ensuing days with peaks of 37.5 C or greater . We also analyzed several related end points . The time to resolution of fever was defined as the number of days elapsed before the first complete day with a temperature less than 37.5 C ( subsequent fevers were not included in this definition ) . Late fever was defined as a temperature greater than 38.2 C occurring after the fever had initially resolved . The time to resolution of febrile neutropenia was defined as the number of days elapsed before the first day with both a temperature less than 37.5 C and a neutrophil count of 1.0 109/L or less ( subsequent days of fever or neutropenia were not included in this definition ) . The prospect ively defined secondary end points of the study were days on study ( hospitalization ) and the incidence of the change of antibiotics . This was an inpatient study ; therefore , all days on study were spent in the hospital . Although some patients were in patients when fever and neutropenia developed and some remained in the hospital after completing the study , the days on study equalled the period of hospitalization for most patients . Patients who remained in the hospital after completing the study did so for reasons other than continued morbidity related to fever and neutropenia . Safety All adverse events were grade d according to World Health Organization criteria [ 19 ] . Data collected included daily clinical evaluation , toxicity grading , and blood examinations ; and urea , electrolytes , creatinine , liver function tests , clotting tests , and urinalysis , all of which were done every fifth day . The numbers of red blood cell and platelet transfusions were also recorded . Deaths that occurred during the study and within 30 days of study completion were recorded , and a blinded assessment was made of any possible contribution to the death by the study drug . Statistical Analyses We used a 1:1 ratio of patients treated with filgrastim to patients receiving placebo . The sample size was chosen to detect a 25 % difference in the protocol -specified primary end points of days of fever and days of neutropenia with 80 % power at a significance level of 0.05 . However , an unplanned interim analysis was done for administrative purpose s , rather than with the intent of early study termination , when 87 patients had completed the study . Therefore , the Purpose Pegylated granulocyte-colony-stimulating factor ( G-CSF ) is frequently used to prevent febrile neutropenia ( FN ) in patients undergoing chemotherapy with a high risk of myelosuppression . This phase II/III study was conducted to determine the adequate dose of pegteograstim , a new formulation of pegylated G-CSF , and to evaluate the efficacy and safety of pegteograstim compared to pegfilgrastim . Methods In the phase II part , 60 breast cancer patients who were undergoing DA ( docetaxel and doxorubicin ) or TAC ( docetaxel , doxorubicin , and cyclophosphamide ) chemotherapy were r and omly selected to receive a single subcutaneous injection of 3.6 or 6.0 mg pegteograstim on day 2 of each chemotherapy cycle . The phase III part was seamlessly started to compare the dose of pegteograstim at selected in phase II with 6.0 mg pegfilgrastim in 117 breast cancer patients . The primary endpoint of both the phase II and III parts was the duration of grade 4 neutropenia in the chemotherapy cycle 1 . Results The mean duration of grade 4 neutropenia for the 3.6 mg pegteograstim ( n = 33 ) was similar to that for the 6.0 mg pegteograstim ( n = 26 ) ( 1.97 ± 1.79 days vs. 1.54 ± 0.95 days , p = 0.33 ) . The 6.0 mg pegteograstim was selected to be compared with the 6.0 mg pegfilgrastim in the phase III part . In the phase III part , the primary analysis revealed that the efficacy of pegteograstim ( n = 56 ) was non-inferior to that of pegfilgrastim ( n = 59 ) [ duration of grade 4 neutropenia , 1.64 ± 1.18 days vs. 1.80 ± 1.05 days ; difference , −0.15 ± 1.11 ( p = 0.36 , 97.5 % confidence intervals = 0.57 and 0.26 ) ] . The time to the absolute neutrophil count ( ANC ) recovery of pegteograstim ( ≥2000/μL ) was significantly shorter than that of pegfilgrastim ( 8.85 ± 1.45 days vs. 9.83 ± 1.20 days , p < 0.0001 ) . Other secondary endpoints showed no significant difference between the two groups . The safety profiles of the two groups did not differ significantly . Conclusions Pegteograstim was shown to be as effective as pegfilgrastim in the reduction of chemotherapy-induced neutropenia in the breast cancer patients who were undergoing chemotherapy with a high risk of myelosuppression A chemotherapy regimen of docetaxel , doxorubicin and cyclophosphamide ( TAC ) has been accepted as a st and ard care because of their superior clinical benefit in early-stage breast cancer patients , but with a higher risk of neutropenia . Pegfilgrastim is a once-per-cycle therapy for prophylactic neutrophil support and neutropenia prevention . There was still a lack of direct evidence s for finding an optimal fixed dose of pegfilgrastim in Chinese breast cancer patients receiving TAC regimen . An open-label , r and omized , phase II study was design ed to compare the effects of pegfilgrastim with filgrastim . Eighteen centers in China enrolled 171 eligible female breast cancer patients with cycles of TAC chemotherapy treatment , r and omized into four arms , received a single subcutaneous injection of pegfilgrastim ( 60 , 100 or 120 µg/kg ) per chemotherapy cycle or daily subcutaneous injections of filgrastim 5 µg/kg 24 h after chemotherapy . Efficacy and safety were analyzed . In ITT population , the mean duration of grade 3 + neutropenia ( neutrophil count < 1.0 × 109/l ) was 2.09 , 1.53 and 1.73 days in patients who received pegfilgrastim 60 , 100 and 120 µg/kg/cycle , respectively , and 1.69 days in patients who received 5 µg/kg/day filgrastim ( P = 0.043 ) . The incidence of grade 3 + neutropenia was 76 , 83 and 74 % for doses of pegfilgrastim and 90 % for filgrastim ( P = 0.409 ) . The results for febrile neutropenia , time to neutrophil recovery and neutrophil profile were also not significantly different between arms . The safety profiles of pegfilgrastim and filgrastim were similar . A single dose of 100 µg/kg once-per-cycle administration of pegfilgrastim provided neutrophil support and a safety profile comparable to daily subcutaneous injections of filgrastim in Chinese breast cancer patients receiving TAC chemotherapy Background PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety . In China ’s registration trial ( C FDA : 2006L01305 ) , we assessed its efficacy and safety against rhG-CSF , and prospect ively explored its value over multiple cycles of chemotherapy . Methods In this open-label , r and omized , multicenter phase 3 study , breast cancer patients ( n = 569 ) were r and omized to receive PEG-rhG-CSF 100 µg/kg , PEG-rhG-CSF 6 mg , or rhG-CSF 5 µg/kg/d after chemotherapy . The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1 . Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2–4 , the incidence of febrile neutropenia , and the safety . Results A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia . Interestingly , a substantial difference was noted during cycle 2 , and the difference became bigger over cycles 3–4 , reaching a statistical significance at cycle 4 in either incidence ( P = 0.0309 ) or duration ( P = 0.0289 ) favoring PEG-rhG-CSF . A significant trend toward a lower incidence of all- grade adverse events was noted at 129 ( 68.98 % ) , 142 ( 75.53 % ) , and 160 ( 82.47 % ) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups , respectively ( P = 0.0085 ) . The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 ( 1.07 % ) , 1/188 ( 0.53 % ) , and 8/194 ( 4.12 % ) , respectively ( P = 0.0477 ) . Additionally , PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan – Meier analysis ( n = 49 , P = 0.153 ) . Conclusions PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy Purpose This multi-center , r and omized , phase III study was conducted to demonstrate the non-inferiority of DA-3031 compared with daily filgrastim in patients during the first cycle of chemotherapy for breast cancer in terms of the duration of severe neutropenia ( DSN ) . Methods Seventy-four patients with breast cancer who were receiving combination chemotherapy with docetaxel , doxorubicin , and cyclophosphamide ( TAC ) were enrolled . All participants were r and omized to receive either daily subcutaneous injections of filgrastim 100 μg/m2/day for up to 10 days or a single subcutaneous injection of DA-3031 at fixed doses of 6 mg on day 2 of each chemotherapy cycle . Results The mean duration of grade 4 ( G4 ) neutropenia in cycle 1 was 2.08 ± 0.85 days for the filgrastim group and 2.28 ± 1.14 days for the DA-3031 group . The difference between groups was 0.2 ± 1.10 days ( 95 % confidence interval ( CI ) = −0.26 , 0.66 ) , which supported non-inferiority . No statistically significant differences were observed in nadir absolute neutrophil count ( ANC ) ( 154.34/mm3 and 161.75/mm3 for the filgrastim and DA-3031 groups , respectively ; P = 0.8414 ) or in time to ANC recovery ( 10.03 ± 0.75 and 9.83 ± 1.56 days in the filgrastim and DA-3031 groups , respectively ; P = 0.0611 ) during cycle 1 . Serious AEs occurred in six ( 15.8 % ) patients receiving filgrastim and in ten ( 27.8 % ) patients receiving DA-3031 ; however , none was determined to be related to the study drug . Conclusions DA-3031 and daily filgrastim are similar in regard to DSN and safety in breast cancer patients receiving TAC chemotherapy Background Neutropenia is a common toxicity in patients receiving myelosuppressive chemotherapy . In this prospect i ve pilot study , we compared the efficacy and safety profiles of pegfilgrastim administered subcutaneously once per cycle and lenograstim administered subcutaneously daily six times per cycle , for primary neutropenia prophylaxis in women with breast cancer receiving adjuvant anthracycline-based chemotherapy . Material s and methods Twenty women were enrolled . All patients received epirubicin 100 mg/m2 with 5-fluorouracil 500 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 and every 21 days thereafter , according to the FEC 100 chemotherapy regimen . Eight patients received a single dose of pegfilgrastim on day 2 , while 12 patients were treated with daily administration of lenograstim from days five to ten . Absolute neutrophil count and duration of grade 3–4 neutropenia were monitored using seriated blood sample s. The incidence of bone pain was evaluated using the visual analog scale ( VAS ) . Results The incidence of grade 3–4 neutropenia was 75 % in patients who received pegfilgrastim , and 25 % in patients who received lenograstim . One case of febrile neutropenia was shown in pegfilgrastim patients . The mean duration of grade 3–4 neutropenia was 2 days in pegfilgrastim group versus 1.4 days in the lenograstim group . Bone pain was present in 37.5 % of pegfilgrastim patients versus 58.3 % of lenograstim patients . The mean duration of bone pain in the pegfilgrastim group was 4 days versus 6 days in the lenograstim group . Conclusion In our experience , a single injection of pegfilgrastim was less effective for controlling neutropenia than six daily injections of lenograstim . The safety profiles of pegfilgrastim and lenograstim were similar with a lower incidence of bone pain in patients treated with pegfilgrastim This r and omized , double-blind comparison demonstrates that biosimilar filgrastim ( EP2006 ) and the US-licensed reference filgrastim are similar with no clinical ly meaningful differences regarding efficacy and safety in prevention of severe neutropenia . Biosimilar filgrastim could represent an important alternative to the reference product , potentially increasing access to filgrastim treatment OBJECTIVES : To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator . METHODS : This phase III non-inferiority study had a r and omized , multicenter , and open-label design . The patients were r and omized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient . In both study arms , filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight . The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle . The secondary endpoints were the duration of grade 4 neutropenia , the generation of anti-filgrastim antibodies , and the rates of adverse events , laboratory abnormalities , febrile neutropenia , and neutropenia of any grade . RESULTS : The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug ; the upper limit of the 90 % confidence interval ( CI ) for the rate of neutropenia between the two groups ( 12.61 % ) was lower than the established margin of non-inferiority . The two treatments were similar with respect to the secondary endpoints and safety . CONCLUSION : The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle . This study supports Anvisa 's approval of the first biosimilar drug manufactured by the Brazilian industry ( Fiprima ® ) BACKGROUND TAC ( docetaxel/doxorubicin/cyclophosphamide ) is associated with high incidences of grade 4 neutropenia and febrile neutropenia ( FN ) . This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC . PATIENTS AND METHODS Patients with stage T2-T4 primary breast cancer were scheduled to receive 6 - 8 cycles of TAC . Primary prophylaxis was : ciprofloxacin 500 mg orally twice daily on days 5 - 14 ( n = 253 patients ; 1478 cycles ) , daily granulocyte colony-stimulating factor ( G-CSF ) ( filgrastim 5 microg/kg/day or lenograstim 150 microg/m(2)/day ) on days 5 - 10 ( n = 377 ; 2400 cycles ) , pegfilgrastim 6 mg on day 2 ( n = 305 ; 1930 cycles ) , or pegfilgrastim plus ciprofloxacin ( n = 321 ; 1890 cycles ) . RESULTS Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN ( 5 % and 7 % versus 18 % and 22 % of patients ; all P < 0.001 ) , grade 4 neutropenia , and leukopenia . Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN ( P < 0.01 versus pegfilgrastim alone ) and fatal neutropenic events . CONCLUSION Ciprofloxacin alone , or daily G-CSF from day 5 - 10 ( as in common practice ) , provided suboptimal protection against FN and related toxic effects in patients receiving TAC . Pegfilgrastim was significantly more effective in this setting , especially if given with ciprofloxacin The purpose of this study was to compare the efficacy and safety of a single subcutaneous injection of pegylated filgrastim with daily filgrastim as a prophylaxis for neutropenia induced by commonly used chemotherapy regimens . Fifteen centers enrolled 337 chemotherapy-naive cancer patients with normal bone marrow function . All patients r and omized into AOB and BOA arms received two cycles of chemotherapy . Patients received a single dose of pegylated filgrastim 100 µg/kg in cycle 1 ( AOB ) or cycle 2 ( BOA ) and daily doses of filgrastim 5 µg/kg/day in cycle 1 ( BOA ) or cycle 2 ( AOB ) . Efficacy and safety parameters were recorded . The primary end point was the rate of protection against grade 4 neutropenia after chemotherapy [ defined as the rate at which the absolute neutrophil count ( ANC ) remained > 0.5 × 109/l throughout the entire cycle ] . Ninety-four percent of patients receiving pegylated filgrastim or filgrastim did not develop grade 4 neutropenia . The incidence of ANC<1.0 × 109/l was 16.0 % ( 50/313 ) after support with either pegylated filgrastim or filgrastim . The incidences of febrile neutropenia and antibiotic administration were similar in both groups . Notably , faster ANC recovery was observed with pegylated filgrastim support . The ANC nadir was also earlier with pegylated filgrastim ( day 7 ) support than with filgrastim support ( day 9 ) , although the depth of nadir was not significantly different . A single subcutaneous injection of pegylated filgrastim 100 & mgr;g/kg provided adequate and safe neutrophil support comparable with daily subcutaneous injections of unmodified filgrastim 5 & mgr;g/kg/day in patients receiving commonly used st and ard-dose mild-to-moderate myelosuppressive chemotherapy regimens Older age is a poor prognosis factor in acute myeloid leukemia ( AML ) . This double-blind trial was design ed to test the hypothesis that granulocyte colony-stimulating factor ( G-CSF ) used as supportive care could improve the treatment of elderly AML patients . Two hundred thirty-four patients 55 or more years of age with a morphologic diagnosis of de novo or secondary AML , French-American-British ( FAB ) M0-M7 , excluding M3 , were r and omly assigned to a st and ard induction regimen ( daunorubicin at 45 mg/m2 intravenously [ IV ] on days 1 through 3 and Ara-C at 200 mg/m2 IV continuous infusion on days 1 through 7 ) plus either placebo or G-CSF ( 400 microg/m2 IV over 30 minutes once daily ) . Results are reported here for 211 central ly confirmed cases of non-M3 AML . The two groups were well balanced in demographic , clinical , and hematological parameters , with median ages of 68 years in the G-CSF and 67 years in the placebo groups . The complete response ( CR ) rate was not significantly better in the G-CSF group : 50 % in the placebo and 41 % in the G-CSF group ( one-tailed P = .89 ) . Median overall survival was also similar , 9 months ( 95 % confidence interval [ CI ] , 7 to 10 months ) in the placebo and 6 months ( 95 % CI , 3 to 8 months ) in the G-CSF arms ( P = .71 ) . We found a significant 15 % reduction in the time to neutrophil recovery in the G-CSF group ( P = .014 ) . G-CSF had no impact on recovery from thrombocytopenia ( P = .80 ) or duration of first hospitalization ( P = .27 ) . When infection complications were evaluated , G-CSF had a beneficial effect on the duration but not on incidence of infection . G-CSF patients had fewer days with fever and shorter duration of antibiotic use . However , there was no difference in the frequency of total documented infections or in the number of fatal infections ( 19 % placebo v 20 % G-CSF ) . In this study of elderly AML patients , G-CSF improved clinical parameters of duration of neutropenia and antibiotic use , but did not change CR rate or survival or shorten hospitalization Background Recombinant granulocyte colony-stimulating factors ( G-CSFs ) such as Filgrastim are used to treat chemotherapy-induced neutropenia . We investigated a new G-CSF , XM02 , and compared it to Neupogen ™ after myelotoxic chemotherapy in breast cancer ( BC ) patients . Methods A total of 348 patients with BC receiving docetaxel/doxorubicin chemotherapy were r and omised to treatment with daily injections ( subcutaneous 5 μg/kg/day ) for at least 5 days and a maximum of 14 days in each cycle of XM02 ( n = 140 ) , Neupogen ™ ( n = 136 ) or placebo ( n = 72 ) . The primary endpoint was the duration of severe neutropenia ( DSN ) in cycle 1 . Results The mean DSN in cycle 1 was 1.1 , 1.1 , and 3.9 days in the XM02 , Neupogen ™ , and placebo group , respectively . Superiority of XM02 over placebo and equivalence of XM02 with Neupogen ™ could be demonstrated . Toxicities were similar between XM02 and Neupogen ™ . Conclusion XM02 was superior to placebo and equivalent to Neupogen ™ in reducing DSN after myelotoxic chemotherapy . Trial Registration Current Controlled Trials IS RCT Pegfilgrastim is a pegylated form of the granulocyte‐colony stimulating factor , filgrastim . Herein , we report the results of a multicentre , r and omized , double‐blind phase III trial comparing the efficacy and safety of pegfilgrastim with filgrastim in patients with malignant lymphoma . Patients were r and omized to receive either a single subcutaneous dose of pegfilgrastim or daily subcutaneous doses of filgrastim on day 4 after the completion of cyclophosphamide , cytarabine , etoposide and dexamethasone ± rituximab ( CHASE(R ) ; day 1–3 ) chemotherapy . The primary endpoint was the duration of severe neutropenia ( DSN ) , defined as the number of days with neutrophil count < 0·5 × 109/l in the first cycle of chemotherapy . A total of 111 lymphoma patients were r and omized to either the pegfilgrastim or filgrastim group . 109 patients received either pegfilgrastim ( n = 54 ) or filgrastim ( n = 55 ) . Efficacy data were available for 107 patients ( pegfilgrastim : n = 53 , filgrastim : n = 54 ) . Both groups were well balanced in terms of gender , age , performance status and other variables . The mean DSN ( ±S.D. ) was 4·5 ( ±1·2 ) and 4·7 ( ±1·3 ) d in the pegfilgrastim and filgrastim groups . No significant difference in safety was observed . This trial verified the non‐inferiority of a single subcutaneous dose of pegfilgrastim compared with daily subcutaneous doses of filgrastim , considering DSN as an indicator PURPOSE We evaluated the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia associated with docetaxel in breast cancer patients . PATIENTS AND METHODS Patients were r and omly assigned to either placebo or pegfilgrastim 6 mg subcutaneously on day 2 of each 21-day chemotherapy cycle of 100 mg/m(2 ) docetaxel . The primary end point was the percentage of patients developing febrile neutropenia ( defined as body temperature > /= 38.2 degrees C and neutrophil count < 0.5 x 10(9)/L on the same day of the fever or the day after ) . Secondary end points were incidence of hospitalizations associated with a diagnosis of febrile neutropenia , intravenous ( IV ) anti-infectives required for febrile neutropenia , and the ability to maintain planned chemotherapy dose on time . Patients with febrile neutropenia were converted to open-label pegfilgrastim in subsequent cycles . RESULTS Nine hundred twenty-eight patients received placebo ( n = 465 ) or pegfilgrastim ( n = 463 ) . Patients receiving pegfilgrastim , compared with patients receiving placebo , had a lower incidence of febrile neutropenia ( 1 % v 17 % , respectively ; P < .001 ) , febrile neutropenia-related hospitalization ( 1 % v 14 % , respectively ; P < .001 ) , and use of IV anti-infectives ( 2 % v 10 % , respectively ; P < .001 ) . The percentage of patients receiving the planned dose on time was similar between patients receiving pegfilgrastim and patients who initially received placebo ( 80 % and 78 % , respectively ) , as would be expected of the study design . Pegfilgrastim was generally well tolerated and safe , and the adverse events reported were typical of this patient population . CONCLUSION First and subsequent cycle use of pegfilgrastim with a moderately myelosuppressive chemotherapy regimen markedly reduced febrile neutropenia , febrile neutropenia-related hospitalizations , and IV anti-infective use BACKGROUND Neutropenia and infection are major dose-limiting side effects of chemotherapy . Previous studies have suggested that recombinant methionyl granulocyte colony-stimulating factor ( G-CSF ) can reduce chemotherapy-related neutropenia in patients with cancer . We conducted a r and omized clinical trial to test this hypothesis and the clinical implication s. METHODS Patients with small-cell lung cancer were enrolled in a multicenter , r and omized , double-blind , placebo-controlled trial of recombinant methionyl G-CSF to study the incidence of infection as manifested by fever with neutropenia ( absolute neutrophil count , less than 1.0 x 10(9 ) per liter , with a temperature greater than or equal to 38.2 degrees C ) result ing from up to six cycles of chemotherapy with cyclophosphamide , doxorubicin , and etoposide . The patients were r and omly assigned to receive either placebo or G-CSF , with treatment beginning on day 4 and continuing through day 17 of a 21-day cycle . RESULTS The safety of the study treatment could be evaluated in 207 of the 211 patients assigned to either drug , and its efficacy in 199 . At least one episode of fever with neutropenia occurred in 77 percent of the placebo group , as compared with 40 percent of the G-CSF group ( P less than 0.001 ) . Over all cycles of chemotherapy , the median duration of grade IV neutropenia ( absolute neutrophil count , less than 0.5 x 10(9 ) per liter ) was six days with placebo as compared with one day with G-CSF . During cycles of blinded treatment , the number of days of treatment with intravenous antibiotics , the number of days of hospitalization , and the incidence of confirmed infections were reduced by approximately 50 percent when G-CSF was given , as compared with placebo . Mild-to-moderate medullary bone pain occurred in 20 percent of the patients receiving G-CSF . CONCLUSIONS The use of G-CSF as an adjunct to chemotherapy in patients with small-cell cancer of the lung was well tolerated and led to reductions in the incidence of fever with neutropenia and culture-confirmed infections ; in the incidence , duration , and severity of grade IV neutropenia ; and in the total number of days of treatment with intravenous antibiotics and days of hospitalization This prospect i ve multicenter study examined whether simultaneous administration of granulocyte colony-stimulating factor ( G-CSF ; Filgrastim ) and induction chemotherapy for adult acute lymphoblastic leukemia ( ALL ) could prevent treatment-related neutropenia , infections , and result ing treatment delays . Seventy-six patients were r and omly assigned to receive either G-CSF ( n = 37 ) or no growth factor ( n = 39 ) in conjunction with a uniform chemotherapy consisting of cyclophosphamide , cytarabine , mercaptopurine , intrathecal methotrexate , and cranial irradiation . The median duration of neutropenia ( absolute neutrophil count < 1 x 10(9)/L ) during chemotherapy was 8 days in patients receiving C-CSF , compared with 12.5 days in the control group ( P < .002 ) . A similar reduction from 11.5 to 7 days was observed in patients with T-ALL receiving additional mediastinal irradiation ( P = .13 ) . Infections occurred in 43 % and 56 % of patients in the G-CSF and control arm , respectively ( P = .25 ) ; the incidence of nonviral infections was reduced by 50 % , from 32 episodes in the control arm to 16 episodes in the G-CSF arm . Prolonged interruptions of chemotherapy administration were less frequent , with delays of 2 weeks or more occurring in only 24 % of patients receiving G-CSF as opposed to 46 % in the control arm ( P = .01 ) . Accordingly , chemotherapy was completed significantly earlier with the use of G-CSF ( 39 v 44 days , P = .008 ) . With a median follow-up of 20 months , the probability of disease-free survival was 0.45 in the G-CSF group and 0.43 in the control group ( P = .34 ) . In conclusion , adult ALL patients appear to benefit by the simultaneous administration of G-CSF with induction chemotherapy because of a significant reduction in the duration of neutropenia , a trend to fewer infections , and a more rapid completion of chemotherapy Abstract This dose-ranging study was conducted to identify the optimal fixed dose of lipegfilgrastim compared with pegfilgrastim 6.0 mg for the provision of neutrophil support during myelosuppressive chemotherapy in patients with breast cancer . A phase 2 study was conducted in which 208 chemotherapy-naive patients were r and omized to receive lipegfilgrastim 3.0 , 4.5 , or 6.0 mg or pegfilgrastim 6.0 mg . Study drugs were administered as a single subcutaneous injection on day 2 of each chemotherapy cycle ( doxorubicin/docetaxel on day 1 for four 3-week cycles ) . The primary outcome measure was duration of severe neutropenia ( DSN ) in cycle 1 . Patients treated with lipegfilgrastim experienced shorter DSN in cycle 1 with higher doses . The mean DSN was 0.76 days in the lipegfilgrastim 6.0-mg group and 0.87 days in the pegfilgrastim 6.0-mg group , with no significant differences between treatment groups . Treatment with lipegfilgrastim 6.0 mg was consistently associated with a higher absolute neutrophil count ( ANC ) at nadir , shorter ANC recovery time , and a similar safety and tolerability profile compared with pegfilgrastim . This phase 2 study demonstrated that lipegfilgrastim 6.0 mg is the optimal dose for patients with breast cancer and provides neutrophil support that is at least equivalent to the st and ard 6.0-mg fixed dose of pegfilgrastim Because of the recommendation to avoid the concomitant administration of growth factors and chemotherapy , there is only limited information on colony-stimulating factor ( CSF ) therapy in acute lymphoblastic leukemia ( ALL ) induction protocol s , in which cytotoxic drugs are administered in divided doses over a prolonged period of time , thus requiring a simultaneous administration of growth factors and chemotherapy . We conducted a prospect i ve , r and omized , controlled study to determine the safety and efficacy of granulocyte colony-stimulating factor ( G-CSF ; filgrastim ) as an adjunct to phase I of induction chemotherapy for adult ALL . Patients ( n = 53 ) were r and omized to receive no growth factor or G-CSF ( 5 microg/kg/d subcutaneously ) starting on day 2 of chemotherapy consisting of daunorubicin ( 45 mg/m2 ) and vincristine ( 1.5 mg/m2 ) on days 1 , 8 , 15 , and 22 ; L-asparaginase ( 2500 U/m2 ) on days 1 through 14 ; and prednisone ( 60 mg/m2 ) on days 1 through 28 . A total of 25 patients in the G-CSF group and 26 patients in the control arm fulfilled the inclusion criteria of the study . G-CSF markedly ameliorated neutropenia because the median proportion of days with neutropenia less than 1,000/microL was 29 % in the G-CSF group as compared with 84 % in the control arm ( P < .00005 ) . The median time to reach absolute neutrophil counts ( ANC ) > or = 1,000/microL was 16 days in G-CSF patients and 26 days in controls ( P < .001 ) . More importantly , G-CSF significantly reduced the incidence of febrile neutropenia ( 12 % v 42 % in controls , P < .05 ) and documented infections ( 40 % v 77 % , P < .05 ) . No significant differences were found with regard to requirements for red blood cell transfusions and platelet concentrates . A total of 24 of 25 ( 96 % ) patients in the G-CSF group and 20 of 25 ( 80 % ) evaluable control patients had complete remission after phase I of induction therapy . We conclude that G-CSF can be safely administered as an adjunct to induction therapy of ALL and is clinical ly beneficial by ameliorating neutropenia and reducing infectious complications This r and omized , double-blind , phase III trial compared granulocyte colony-stimulating factor ( G-CSF ; filgrastim ) and leridistim ( formerly myelopoietin ) , a chimeric dual agonist that binds both G-CSF and interleukin-3 receptors , for the prevention of neutropenic complications in patients with breast cancer receiving TAC ( docetaxel/doxorubicin/cyclophosphamide ) chemotherapy . Patients with metastatic ( 44 % ) or localized breast cancer ( 56 % ) were r and omized to G-CSF 5 microg/kg subcutaneously ( s.c . ) daily ( n = 135 ) , leridistim 5 microg/kg s.c . daily ( n = 139 ) , or leridistim 10 microg/kg s.c . every other day alternating with placebo ( n = 139 ) . Following administration of TAC ( docetaxel 75 mg/m2 , doxorubicin 50 mg/m2 , cyclophosphamide 500 mg/m2 ) on day 1 , patients received growth factor beginning on day 2 until the postnadir absolute neutrophil count exceeded 1500 cells/ microL. Chemotherapy cycles were repeated every 21 days . The incidence of febrile neutropenia was 7 % in the G-CSF arm , 19 % in the daily leridistim arm ( P = 0.003 for comparison with G-CSF ) and 22 % in the alternate-day leridistim arm ( P < 0.001 for comparison with G-CSF ) . There was no significant difference between treatment arms in the cumulative percentage of patients experiencing grade 4 neutropenia at some point during therapy ( 85%-88 % ) . However , grade 4 neutropenia occurred in 53 % of cycles in the G-CSF cohort , 61 % of cycles in the daily leridistim group ( P = 0.063 for comparison with G-CSF ) , and 63 % of cycles in the alternate-day leridistim group ( P = 0.015 for comparison with G-CSF ) . We conclude that G-CSF is superior to leridistim in the prevention of febrile neutropenia in patients with advanced breast cancer receiving TAC chemotherapy . The up-front prophylactic use of G-CSF is a reasonable supportive therapy for patients treated with docetaxel/anthracycline-based combination chemotherapy Summary . To investigate the efficacy and safety of granulocyte colony‐stimulating factor ( G‐CSF ) in patients with acute myelogenous leukaemia , a multicentre r and omized study was performed . From October 1993 to September 1996 , 270 patients with newly diagnosed acute myelogenous leukaemia were r and omized to G‐CSF or control groups after remission induction therapy . The G‐CSF group received G‐CSF ( Filgrastim ) from 48 h after the completing chemotherapy until the absolute neutrophil count exceeded 1·5 × 109/l . The control group did not receive G‐CSF unless severe infection occurred . There were 245 evaluable patients ( 120 and 125 in the G‐CSF and control groups respectively ) . The complete remission rate was similar in the G‐CSF and control groups ( 80·8 % versus 76·8 % ) , as was the 5‐year probability of disease‐free survival ( 34·5 % versus 33·6 % ) and overall survival ( 42·7 % versus 35·6 % ) . Neutrophil recovery was significantly faster in the G‐CSF group than in the control group ( 12 d versus 18 d , P = 0·0001 ) . The median duration of febrile neutropenia was significantly shorter in the G‐CSF group than in the control group ( 3 d versus 4 d , P = 0·0001 ) . In conclusion , prophylactic administration of G‐CSF after remission induction therapy for acute myelogenous leukaemia is safe and useful even in patients without infection on completing chemotherapy PURPOSE This multicenter , r and omized , double-blind , active-control study was design ed to determine whether a single subcutaneous injection of pegfilgrastim ( SD/01 , sustained- duration filgrastim ; 100 microg/kg ) is as safe and effective as daily filgrastim ( 5 microg/kg/d ) for reducing neutropenia in patients who received four cycles of myelosuppressive chemotherapy . PATIENTS AND METHODS Sixty-two centers enrolled 310 patients who received chemotherapy with docetaxel 75 mg/m(2 ) and doxorubicin 60 mg/m(2 ) on day 1 of each cycle for a maximum of four cycles . Patients were r and omized to receive on day 2 either a single subcutaneous injection of pegfilgrastim 100 microg/kg per chemotherapy cycle ( 154 patients ) or daily subcutaneous injections of filgrastim 5 microg/kg/d ( 156 patients ) . Absolute neutrophil count ( ANC ) , duration of grade 4 neutropenia , and safety parameters were monitored . RESULTS One dose of pegfilgrastim per chemotherapy cycle was comparable to daily subcutaneous injections of filgrastim with regard to all efficacy end points , including the duration of severe neutropenia and the depth of ANC nadir in all cycles . Febrile neutropenia across all cycles occurred less often in patients who received pegfilgrastim . The difference in the mean duration of severe neutropenia between the pegfilgrastim and filgrastim treatment groups was less than 1 day . Pegfilgrastim was safe and well tolerated , and it was similar to filgrastim . Adverse event profiles in the pegfilgrastim and filgrastim groups were similar . CONCLUSION A single injection of pegfilgrastim 100 microg/kg per cycle was as safe and effective as daily injections of filgrastim 5 microg/kg/d in reducing neutropenia and its complications in patients who received four cycles of doxorubicin 60 mg/m(2 ) and docetaxel 75 mg/m(2 ) Aim : This r and omized , double-blind trial compared proposed biosimilar LA-EP2006 with reference pegfilgrastim in women receiving chemotherapy for breast cancer ( PROTECT-1 ) . Patients & methods : Women ( ≥18 years ) were r and omized to receive LA-EP2006 ( n = 159 ) or reference ( n = 157 ) pegfilgrastim ( Neulasta ® , Amgen ) for ≤6 cycles of (neo)-adjuvant TAC chemotherapy . Primary end point was duration of severe neutropenia ( DSN ) during cycle 1 ( number of consecutive days with absolute neutrophil count < 0.5 × 109/l ) with equivalence confirmed if 90 % and 95 % CIs were within a ±1 day margin . Results : For DSN , LA-EP2006 was equivalent to reference ( difference : 0.07 days ; 90 % CI : -0.09–0.23 ; 95 % CI : -0.12–0.26 ) . Conclusion : LA-EP2006 and reference pegfilgrastim showed no clinical ly meaningful differences regarding efficacy and safety in breast cancer patients receiving chemotherapy The aim of this study was to determine the usefulness of recombinant human granulocyte colony stimulating factor ( r-metHuG-CSF ) following conventional chemotherapy for small cell lung cancer . 130 previously untreated patients were r and omised to receive either r-metHuG-CSF ( 230 micrograms/m2 ) or placebo on days 4 - 17 following CDE ( cyclophosphamide , doxorubicin and etoposide ) chemotherapy . Over all cycles , 53 % of 64 patients on placebo and only 26 % of 65 patients on r-metHuG-CSF had at least one experience of neutropenia with fever defined as a neutrophil count less than 1.0 x 10(9)/l and a temperature > or = 38.2 degrees C ( P < 0.002 ) . It result ed in a reduction in the requirement for parenteral antibiotics from 58 % in placebo patients compared with 37 % in the r-metHuG-CSF group ( P < 0.02 ) , and a significant reduction in the incidence of infection-related hospitalisation . Chemotherapy doses were reduced by 15 % or more at least once in 61 % of the placebo group compared with 29 % in the r-metHuG-CSF group ( P < 0.001 ) . 47 % of the patients treated with placebo and 29 % of the patients treated with r-metHuG-CSF experienced at least one cycle with a delay of 2 days or more in the administration of chemotherapy ( P < 0.04 ) . r-metHuG-CSF was well tolerated . There were no significant differences between the two groups in terms of response or survival Purpose The aim of this study was to demonstrate lipegfilgrastim superiority versus placebo in adults with non-small cell lung cancer receiving myelosuppressive chemotherapy . Methods This phase III , double-blind study r and omized chemotherapy-naive patients to receive cisplatin and etoposide with either lipegfilgrastim 6 mg or placebo . Because of the placebo control , patients at individual high risk for febrile neutropenia ( FN ; ≥20 % ) were excluded . Study drug was administered on day 4 ( 24 h after chemotherapy ) of a 21-day cycle for ≤4 cycles . Primary efficacy measure was FN incidence in cycle 1 . Secondary assessment s included duration of severe neutropenia ( DSN ) , absolute neutrophil count ( ANC ) profile , and adverse events ( AEs ) . Results The study included 375 patients ( lipegfilgrastim , n = 250 ; placebo , n = 125 ) . Lipegfilgrastim superiority for FN incidence in cycle 1 was not achieved but incidence was lower ( 2.4 % ) versus placebo ( 5.6 % ) . Cycle 1 mean DSN was significantly shorter for lipegfilgrastim ( 0.6 ± 1.1 days ) versus placebo ( 2.3 ± 0.5 days ; p < 0.0001 ) . Incidence of severe neutropenia was significantly lower for lipegfilgrastim versus placebo overall and in each cycle ( all , p < 0.0001 ) . Mean ANC nadir was lowest in cycle 1 but significantly higher for lipegfilgrastim ( 1.60 ± 1.64 ) than placebo ( 0.67 ± 0.85 ; p < 0.0001 ) . Mean time to ANC recovery was shorter with lipegfilgrastim in each cycle . Treatment-emergent AEs were similar between treatment groups . Conclusions Lipegfilgrastim was not statistically superior to placebo for incidence of FN in cycle 1 , but was more effective in reducing incidence of severe neutropenia , DSN , and time to ANC recovery , with an acceptable safety profile.Controlled-trials.com identifier : IS RCT N55761467 The effect of granulocyte colony-stimulating factor ( G-CSF ) on neutropenia , infection , and cytotoxic chemotherapy administration was studied in a r and omized trial in patients receiving intensive weekly chemotherapy for non-Hodgkin 's lymphoma ( NHL ) . Eighty patients ( aged 16 to 71 years ) with high- grade NHL ( Kiel ) of any stage were r and omized to receive VAPEC-B chemotherapy alone ( 39 patients ) or with G-CSF administered as a daily subcutaneous dose of 230 micrograms/m2 ( 41 patients ) . Prophylactic ketoconazole and cotrimoxazole were administered to all patients throughout treatment . The protocol specified identical dose modification and antibiotic treatment criteria bor both groups . Neutropenia ( absolute neutrophil count [ ANC ] less than 1.0 x 10(9)/L ) occurred in 15 of 41 ( 37 % ) of the G-CSF-treated patients and in 33 of 39 ( 85 % ) of the controls , giving a relative risk for control patients of 2.31 ( 95 % confidence interval [ CI ] , [ 1.51 , 3.54 ] ; P = .00001 ) . Fever ( greater than or equal to 37.5 degrees C ) with neutropenia ( ANC less than 1.0 x 10(9)/L ) occurred in 9 of 41 ( 22 % ) of the G-CSF group and in 17 of 39 ( 44 % ) of the controls ( relative risk for control , 2.26 ; 95 % CI [ 1.01 , 5.06 ] ; P = .04 ) . There were fewer treatment delays , with shorter duration ( P = .01 ) in patients receiving G-CSF . Chemotherapy doses were reduced in 4 of 41 ( 10 % ) of the G-CSF patients and 13 of 39 ( 33 % ) of the controls ( P = .01 ) . The dose intensity of cytotoxic chemotherapy was significantly increased in patients receiving G-CSF ( median of 95 % in G-CSF group compared with 83 % in control patients ) . Three vascular deaths occurred in the G-CSF group . Delays in the control group most commonly result ed from neutropenia ( 19 patients , compared with 2 patients in the G-CSF-treated group , P = .000007 ) . Severe mucositis was the major dose-limiting toxicity in G-CSF-treated patients , but did not occur more frequently than in controls ( 15 patients in each group ) . Overall , patients r and omized to receive G-CSF achieved a greater dose intensity than control patients , but this did not result in significant differences in drug toxicity ( other than neutropenia ) , intravenous antibiotic usage , or hospitalization between the two groups Age is an important prognostic parameter , especially in patients with advanced high- grade non-Hodgkin 's lymphoma ( HG-NHL ) who require more intensive and extensive therapy for any possible chance of cure . We investigated the potential of granulocyte colony-stimulating factor ( G-CSF ) for reducing myelotoxicity , which is the most important dose-limiting factor for chemotherapy . Between March 1993 and June 1995 , 158 previously untreated patients 60 years and older with HG-NHL were included in a cooperative r and omized comparative trial and treated with a combination therapy including VNCOP-B ( cyclophosphamide , mitoxantrone , vincristine , etoposide , bleomycin , and prednisone ) with or without G-CSF . G-CSF was administered at 5 microg/kg/d throughout the treatment starting on day 3 of every week for 5 consecutive days . Of the 158 patients registered for the trial , 149 patients were evaluable : 77 received VNCOP-B plus G-CSF and 72 received VNCOP-B alone . The overall response rate was 81.5 % , with complete response in 59 % : 60 % in the VNCOP-B plus G-CSF group , and 58 % in the VNCOP-B group . At 30 months ( median 24 months ) , 68 % of all complete responders were alive without disease in the G-CSF group and 65 % in the control group . Neutropenia occurred in 18 out of 77 ( 23 % ) of the G-CSF treated patients and in 40 out of 72 ( 55.5 % ) of the controls ( P = .00005 ) . Clinical ly relevant infections occurred in 4 out of 77 ( 5 % ) of the G-CSF group and in 15 out of 72 ( 21 % ) of the controls ( P = .004 ) . The delivered dose intensity was higher in patients receiving G-CSF ( 95 % v 85 % ) , but the difference was not statistically significant . Our data show that VNCOP-B is a feasible and effective regimen in elderly HG-NHL patients , and that the use of G-CSF reduces infection and neutropenia rates without producing any significant modifications to the dose intensity , CR rate , and relapse-free survival curve Purpose : To compare the effectiveness , tolerance , and pharmacokinetics of a single dose of pegfilgrastim to daily filgrastim in children and young adults with sarcomas treated with dose-intensive combination chemotherapy . Experimental Design : Patients were r and omized to receive a single dose of 100 mcg/kg of pegfilgrastim s.c . or 5 mcg/kg/day of filgrastim s.c . , daily until neutrophil recovery after two treatment cycles with vincristine , doxorubicin , and cyclophosphamide ( VDC ) and two cycles of etoposide and ifosfamide ( IE ) . The duration of severe neutropenia ( absolute neutrophil count , ≤500/mcL ) during cycles 1 to 4 and cycle duration for all cycles were compared . Pharmacokinetics of pegfilgrastim and filgrastim and CD34 + stem cell mobilization were studied on cycle 1 . Growth factor – related toxicity , transfusions , and episodes of fever and neutropenia and infections were collected for cycles 1 to 4 . Results : Thirty-four patients ( median age , 20 years ; range 3.8 - 25.8 ) were enrolled , and 32 completed cycles 1 to 4 . The median ( range ) duration of absolute neutrophil count of < 500/mcL was 5.5 ( 3 - 8 ) days for pegfilgrastim and 6 ( 0 - 9 ) days for filgrastim ( P = 0.76 ) after VDC , and 1.5 ( 0 - 4 ) days for pegfilgrastim and 3.75 ( 0 - 6.5 ) days for filgrastim ( P = 0.11 ) after IE . More episodes of febrile neutropenia and documented infections occurred on the filgrastim arm . Serum pegfilgrastim concentrations were highly variable . Pegfilgrastim apparent clearance ( 11 mL/h/kg ) was similar to that reported in adults . Conclusion : A single dose per cycle of pegfilgrastim was well tolerated and may be as effective as daily filgrastim based on the duration of severe neutropenia and number of episodes of febrile neutropenia and documented infections after dose-intensive treatment with VDC and IE . ( Clin Cancer Res 2009;15(23):7361–7 Abstract Background Lipegfilgrastim is a novel glyco-pegylated granulocyte-colony stimulating factor in development for neutropenia prophylaxis in cancer patients receiving chemotherapy . This phase III , double-blind , r and omized , active-controlled , noninferiority trial compared the efficacy and safety of lipegfilgrastim versus pegfilgrastim in chemotherapy-naïve breast cancer patients receiving doxorubicin/docetaxel chemotherapy . Methods Patients with high-risk stage II , III , or IV breast cancer and an absolute neutrophil count ≥1.5 × 109 cells/L were r and omized to a single 6-mg subcutaneous injection of lipegfilgrastim ( n = 101 ) or pegfilgrastim ( n = 101 ) on day 2 of each 21-day chemotherapy cycle ( 4 cycles maximum ) . The primary efficacy endpoint was the duration of severe neutropenia during cycle 1 . Results Cycle 1 : The mean duration of severe neutropenia for the lipegfilgrastim and pegfilgrastim groups was 0.7 and 0.8 days , respectively ( λ = −0.218 [ 95 % confidence interval : –0.498 % , 0.062 % ] , p = 0.126 ) , and no severe neutropenia was observed in 56 % and 49 % of patients in the lipegfilgrastim and pegfilgrastim groups , respectively . All cycles : In the efficacy population , febrile neutropenia occurred in three pegfilgrastim-treated patients ( all in cycle 1 ) and zero lipegfilgrastim-treated patients . Drug-related adverse events in the safety population were reported in 28 % and 26 % of patients in the lipegfilgrastim and pegfilgrastim groups , respectively . Conclusion This study demonstrates that lipegfilgrastim 6 mg is as effective as pegfilgrastim in reducing neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy . Trial Registration Eudra EEACTA200901599910 The study protocol , two global amendments ( Nos. 1 and 2 ) , informed consent documents , and other appropriate study -related documents were review ed and approved by the Ministry of Health of Ukraine Central Ethics Committee and local independent ethics committees ( IECs ) Pegfilgrastim is composed of the protein filgrastim to which a 20-kDa polyethylene glycol ( PEG ) is covalently bound at the N-terminal residue result ing in decreased renal clearance and increased plasma half-life compared with filgrastim . This open-label , r and omized , phase 2 study compared two doses of single administration pegfilgrastim ( 60 and 100 μg/kg ) with daily doses of filgrastim ( 5 μg/kg/day ) or no cytokine treatment after st and ard CHOP ( cyclophosphamide , doxorubicin , vincristine and prednisolone ) chemotherapy for non-Hodgkin 's lymphoma in 50 elderly patients . The primary endpoint was the duration of grade 4 ( severe ) neutropenia ( absolute neutrophil count < 0.5 × 109/l ) in cycle 1 . Duration of grade 4 neutropenia in cycle 1 was 2.2 ( SD 1.2 ) , 1.5 ( SD 1.1 ) , 0.8 ( 1.2 ) and 5.0 ( 2.0 ) days for patients who received pegfilgrastim 60 μg/kg , pegfilgrastim 100 μg/kg , filgrastim 5 μg/kg and no cytokine , respectively . The baseline characteristics of the pegfilgrastim and filgrastim groups were imbalanced with increased bone-marrow involvement and prior therapy in the former . When the treatment groups were balanced for these risk factors , duration of grade 4 neutropenia was comparable with 2.0 and 3.0 vs. 0.6 and 0.5 days for pegfilgrastim 100 μg/kg and filgrastim patients with and without these risk factors , respectively . The incidence of febrile neutropenia ( defined as ANC < 0:5 × 109/l and temperature > 38.2 ° C ) was low ( 10 % of patients ) . Pegfilgrastim was well tolerated with a safety profile similar to daily filgrastim . Once per chemotherapy cycle administration of pegfilgrastim was comparable to filgrastim in this clinical setting e20587 Background : We evaluated the safety and efficacy of a single fixed 6 mg dose of pegfilgrastim ( a pegylated version of filgrastim ) per cycle of chemotherapy , compared with daily administration of filgrastim , in the provision of neutrophil support . METHODS Patients with carcinoma of breast , less than 65 yrs with ECOG performance status 0 or 1 treated at our institution were r and omized to receive either a single 6 mg subcutaneous ( s.c . ) injection of pegfilgrastim or daily 5 mg/kg s.c . injections of filgrastim , after adjuvant or neoadjuvant chemotherapy with doxorubicin , cyclophosphamide and docetaxel ( 60 mg/m , 600 mg/m2 and 75 mg/m2 , respectively)q3 wk . Duration of grade 4 neutropenia ( DSN ) , incidence of febrile neutropenia ( FN ) , grade 4 neutropenia ( SN ) , IV anti-infective use ( IV ) , hospitalization and adverse events like bony pain ( BP ) , anemia & thrombocytopenias were assessed as safety endpoints . RESULTS 71 patients were analyzed from Aug 2007 to Dec 2008 . The median age in pegfilgrastim group is 58 years and filgrastim is 57 years respectively . Results are shown ( Table ) . The mean duration of grade 4 neutropenia ( DSN ) in cycle 1 was 2.0 and 1.7 days for the pegfilgrastim and filgrastim groups , respectively . Results for all efficacy end points in cycles 2 - 6 were consistent with the results from cycle 1 . A trend towards a lower incidence of febrile neutropenia was noted across all cycles with pegfilgrastim compared with filgrastim ( 10.7 % versus 18.6 % , respectively ) . CONCLUSIONS A single fixed dose of pegfilgrastim administered once per cycle of chemotherapy was comparable to multiple daily injections of filgrastim . [ Table : see text ] No significant financial relationships to disclose This r and omized phase 2 study explored the feasibility of delivering four to six cycles of the dose-intensified regimen FEC-100 ( 5-fluorouracil , epirubicin , and cyclophosphamide ) to elderly patients with stage II-III breast cancer , using pegfilgrastim for neutrophil support . Sixty patients aged 65 - 77 years received single 6 mg doses of pegfilgrastim on day 2 of FEC-100 , either as primary prophylaxis ( all cycles : PP ) , or as secondary prophylaxis ( all cycles following a neutropenic event : SP ) . Neutropenic events ( a composite endpoint that included grade 3 neutropenia+fever , grade 4 neutropenia , infectious complication requiring systemic anti-infectives and chemotherapy dose delay/reduction ) occurred in 24/30 ( 80 % ) of the PP and 21/29 ( 72 % ) of the SP group in the first cycle . Most patients received all chemotherapy cycles at full dose on schedule ( 26/30 [ 87 % ] PP ; 20/29 [ 69 % ] SP ) . These data indicate that delivery of FEC-100 is feasible with pegfilgrastim support in elderly breast cancer patients BACKGROUND Adding irinotecan and /or oxaliplatin to every-2-week 5-fluorouracil (5-FU)/leucovorin ( LV ) prolongs survival in patients with colorectal cancer ( CRC ) but increases neutropenia frequency . Pegfilgrastim is indicated to decrease infection as manifested by febrile neutropenia ( FN ) in patients receiving chemotherapy at > 14-day intervals . This r and omized , placebo-controlled phase II study examined pegfilgrastim efficacy and safety in patients with CRC receiving every-2-week chemotherapy . PATIENTS AND METHODS Patients with CRC were r and omized 1:1 to pegfilgrastim 6 mg or placebo administered per-cycle on day 4 . R and omization was stratified by chemotherapy regimen ( patients received every-2-week FOLFOX4 [ 5-FU/LV/oxaliplatin ] , FOLFIRI [ 5-FU/LV/irinotecan ] , or FOIL [ 5-FU/LV/oxaliplatin/irinotecan ] at physician discretion ) . The primary endpoint was incidence of grade 3/4 neutropenia . Secondary endpoints included incidence of grade 3/4 FN and adverse events . After 4 cycles of study treatment , progression-free survival ( PFS ) and overall survival ( OS ) were followed for < or= 2 years in long-term follow-up . RESULTS Of 241 eligible patients analyzed , 118 were in the placebo and 123 in the pegfilgrastim group . In the treatment period , the odds ratio for grade 3/4 neutropenia for pegfilgrastim versus placebo was 0.19 ( 95 % CI , 0.10 - 0.37 ; P < .001 ) ; grade 3/4 FN incidence was also significantly lower in pegfilgrastim-treated patients ( 2 % ) compared with placebo-treated patients ( 8 % ; P = .04 ) . Pegfilgrastim was well tolerated , with leukocyte counts remaining stable during cycles 2 - 4 . In long-term follow-up , both treatment groups had similar PFS and OS . CONCLUSION Pegfilgrastim was well tolerated in patients with CRC receiving every-2-week chemotherapy and significantly reduced neutropenia and FN compared with placebo , though FN was uncommon in both treatment groups . Results suggest that pegfilgrastim administration is feasible in CRC patients receiving every-2-week chemotherapy This study evaluated the effect of glycosylated recombinant human granulocyte colony-stimulating factor ( rHuG-CSF ; lenograstim ) on neutrophil granulocyte counts and on cells of other haematopoietic lineages in 66 patients with solid cancer or lymphoma who received myelosuppressive chemotherapy . Beginning 1 day after completion of chemotherapy , patients received lenograstim ( at dosages of 0.5 , 2 , 5 or 10 micrograms/kg ) or vehicle subcutaneously once daily for 14 consecutive days . Compared with vehicle , lenograstim significantly accelerated neutrophil recovery after chemotherapy in a dose-dependent manner . Mean neutrophil counts recovered to > 1.0 x 10(9 ) cells/l by day 13 in the vehicle group compared with days 11 , 10 , 8 and 7 in the 0.5 , 2 , 5 and 10 micrograms/kg lenograstim groups , respectively . Doses of 0.5 and 2 micrograms/kg of lenograstim had a significant effect on the duration of neutropenia ( < 1.0 x 10(9 ) cells/l ) , the area under the absolute neutrophil count ( ANC ) curve and the time to ANC nadir . The dose of 5 micrograms/kg additionally decreased the total area of neutropenia and gave the narrowest range of values for all neutrophil parameters , while the 10 micrograms/kg dose brought no added benefit . A dose-response effect of lenograstim on time to neutrophil recovery was observed both for patients who received chemotherapy on a single day ( n = 35 ) and for those who received chemotherapy over several days ( n = 29 ) . Based on these findings , a dose of 5 micrograms/kg/day was chosen for further trials Recombinant granulocyte colony-stimulating factors ( G-CSFs ) such as filgrastim or lenograstim are being used to treat chemotherapy-induced neutropenia . The aim of the present study was to investigate a new G-CSF , XM02 , in comparison to filgrastim in terms of safety and efficacy in the prevention of chemotherapy-induced neutropenia in non-Hodgkin-lymphoma ( NHL ) . A total of 92 patients receiving chemotherapy were r and omised in cycle 1 to treatment with daily injections ( subcutaneous 5 µg/kg/day ) of XM02 ( n = 63 ) or filgrastim ( n = 29 ) for at least 5 days and a maximum of 14 days . In subsequent cycles , all patients received XM02 . The mean duration of severe neutropenia ( DSN ) was 0.5 and 0.9 days in cycle 1 for XM02 and filgrastim , respectively ( p = 0.1055 ) . In cycle 1 , the incidence of febrile neutropenia ( FN ) was 11.1 % for XM02 and 20.7 % for filgrastim ( p = 0.1232 ) . The adverse event profile was similar between XM02 and filgrastim . XM02 demonstrated equivalent efficacy and similar safety profile as the reference medication filgrastim . Treatment with XM02 is as beneficial as filgrastim in ameliorating severe neutropenia and FN in patients with NHL receiving chemotherapy . XM02 is safe and well tolerated in the doses applied in this study OBJECTIVES This study aim ed to evaluate the efficacy and safety of once-per-cycle balugrastim versus pegfilgrastim for neutrophil support in breast cancer patients receiving myelosuppressive chemotherapy . METHODS Breast cancer patients ( n = 256 ) were r and omized to 40 or 50 mg of subcutaneous balugrastim or 6 mg of pegfilgrastim ≈24 hours after chemotherapy ( 60 mg/m(2 ) doxorubicin and 75 mg/m(2 ) docetaxel , every 21 days for up to 4 cycles ) . The primary efficacy parameter was the duration of severe neutropenia ( DSN ) in cycle 1 . Secondary parameters included DSN ( cycles 2 - 4 ) , absolute neutrophil count ( ANC ) nadir , febrile neutropenia rates , and time to ANC recovery ( cycles 1 - 4 ) . Safety , pharmacokinetics , and immunogenicity were assessed . RESULTS Mean cycle 1 DSN was 1.0 day with 40 mg of balugrastim , 1.3 with 50 mg of balugrastim , and 1.2 with pegfilgrastim ( upper limit of 95 % confidence intervals for between-group DSN differences was < 1.0 day for both balugrastim doses versus pegfilgrastim ) . Between-group efficacy parameters were comparable except for time to ANC recovery in cycle 1 ( 40 mg of balugrastim , 2.0 days ; 50 mg of balugrastim , 2.1 ; pegfilgrastim , 2.6 ) . Median terminal elimination half-life was ≈37 hours for 40 mg of balugrastim , ≈36 for 50 mg of balugrastim , and ≈45 for pegfilgrastim . Antibody response to balugrastim was low and transient , with no neutralizing effect . CONCLUSION Once-per-cycle balugrastim is not inferior to pegfilgrastim in reducing cycle 1 DSN in breast cancer patients receiving chemotherapy ; both drugs have comparable safety profiles . IMPLICATION S FOR PRACTICE This paper provides efficacy and safety data for a new , once-per-cycle granulocyte colony-stimulating factor , balugrastim , for the prevention of chemotherapy-induced neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy . In this phase III trial , balugrastim was shown to be not inferior to pegfilgrastim in the duration of severe neutropenia in cycle 1 of doxorubicin/docetaxel chemotherapy , and the safety profiles of the two agents were similar . Once-per-cycle balugrastim is a safe and effective alternative to pegfilgrastim for hematopoietic support in patients with breast cancer receiving myelosuppressive chemotherapy associated with a greater than 20 % risk of developing febrile neutropenia This study was intended to ascertain whether the adjunctive administration of filgrastim ( r metHuG-CSF , Amgen ) would influence the dose intensity of chemotherapy or the morbidity of myelosuppression in patients receiving MOPP or MOPP/EVAP hybrid chemotherapy for Hodgkin 's disease . In a prospect i ve r and omized trial , two regimens for the treatment of Hodgkin 's disease were compared . The sub study described here r and omized patients receiving either regimen to receive filgrastim on the days when chemotherapy was not administered . During chemotherapy , parameters of myelosuppression were documented , including dose delays , the severity and duration of neutrophil and platelet nadirs , infective episodes , and result ing hospital admissions . In the MOPP arm , 13/25 eligible patients , and , in the MOPP/EVAP arm , 12/22 eligible patients , received filgrastim . The use of filgrastim made no statistically significant difference to the administered dose intensity for either MOPP ( P = 0.57 , 95 % confidence interval ( CI ) 15-point increase to 8-point reduction ) or MOPP/EVAP ( P = 0.53 ; 95 % CI 7-point increase to 11-point reduction ) . In patients receiving MOPP , filgrastim reduced the median duration of leucopenia ( P = 0.007 ) and the severity of the white blood cell nadir ( P = 0.036 ) ; however , no statistically significant effect ( at the 5 % level ) was seen in platelet or haemoglobin nadirs , the number of days of in-patient hospitalization , the number of admissions for infective complications , the incidence , grade or duration of infections , or the incidence of febrile neutropenia . In patients receiving MOPP/EVAP , filgrastim had no significant effect on the duration or depth of leucopenia but was associated with a reduction in the median haemoglobin ( P = 0.002 ) and platelet nadirs ( P = 0.015 ) . No effect on the above listed sequelae of myelosuppression was influenced by the administration of filgrastim . This study , although small , suggests that the routine use of filgrastim , aim ed at influencing the administered dose intensity of conventional dose chemotherapy in Hodgkin 's disease , is not warranted This phase III study was conducted to evaluate the usefulness of lenograstim as support for ACE ( doxorubicin , cyclophosphamide , and etoposide ) chemotherapy in previously untreated patients with small-cell lung cancer . Patients were r and omized to receive up to six 3-week cycles of either ACE alone ( n = 139 ) or ACE with lenograstim support ( 150 microg/m2/day subcutaneously , days 4 - 13 , n = 141 ) . Compared with the chemotherapy-alone group , the lenograstim support group was more likely to achieve neutrophil recovery ( absolute neutrophil count , > or = 1.5 x 10(9 ) cells/l ) by day 14 ( 95.8 - 100 % vs. 14.3 - 24.1 % across the cycles ) and less likely to experience at least one infectious episode ( 36.7 vs. 54.0 % ; p = 0.004 ) , chemotherapy delay ( 51.8 vs. 56.2 % ; NS ) , or dose reduction ( 17.3 vs. 27.7 % ; p = 0.037 ) . Objective response and event-free and overall survival rates were similar . Lenograstim was well tolerated . Lenograstim may allow the interval between cycles of ACE to be reduced to 2 weeks ; such dose intensification may lead to more favorable objective response and survival rates Overall chemotherapeutic treatment results in pediatric acute lymphoblastic leukemia ( ALL ) are good , with event-free survival ( EFS ) rates over 70 % . However , for a subset of patients characterized by high-risk ( HR ) features the outcome is less favorable , with EFS rates below 50 % . Intensification of chemotherapy may improve the outcome for those patients , but increased toxicity , particularly myelosuppression , limits the escalation of dose intensity . Recombinant methionyl human granulocyte colony-stimulating factor ( r-metHuG-CSF ) is known to reduce myelosuppression after cancer chemotherapy in adults . The objective of this study was to examine the effect of r-metHuG-CSF on myelosuppression in HR pediatric ALL patients and on the overall response rate to chemotherapy . Patients with HR pediatric ALL were r and omized to receive nine alternating cycles of chemotherapy according to the German ALL-Berlin-Frankfurt-Münster 90 protocol either alone or followed by r-metHuG-CSF administered prophylactically at a dose of 5 microg/kg/d subcutaneously . In both groups , the planned interval between chemotherapy courses was a minimum of 21 days . We report here interim results of 34 patients . The incidence of febrile neutropenia ( absolute neutrophil count < 0.5 x 10(9)/L and oral temperature > or = 38.5 degrees C ) was 17 % in children receiving r-metHuG-CSF , as compared with 40 % in the control group ( P = .007 ) . In addition , the median total duration of febrile neutropenia was reduced from 20.3 to 6.2 days per patient ( P = .02 ) . Culture-confirmed infections occurred less frequently in the r-metHuG-CSF group ( 8 % v 15 % ; P = .04 ) , and the total duration of intravenous antibiotic use was significantly reduced from 32.2 days to 18.2 days per patient ( P = .02 ) . A tighter adherence to the planned treatment schedule was also facilitated by r-metHuG-CSF ( P = .007 ) . With a median follow-up of 3.3 years , the estimated EFS of 4 years is 41 % + /- 12 % . In conclusion , r-metHuG-CSF administered prophylactically in the interval between chemotherapy courses significantly reduced febrile neutropenia , culture-confirmed infections , and duration of intravenous antibiotic administration and allowed for tighter adherence to the treatment schedule Summary Background s A pegylated form of recombinant granulocyte-colony stimulating factor ( G-CSF ) was developed for prophylactic use in breast cancer . The aim of this study was to evaluate the efficacy and safety of once-per-cycle DA-3031 in patients receiving chemotherapy for breast cancer . Methods A total of 61 patients receiving docetaxel , doxorubicin , and cyclophosphamide ( TAC ) chemotherapy were r and omized in cycle 1 to receive daily injections of filgrastim ( 100 μg/m2 ) or a single subcutaneous injection of pegylated filgrastim DA-3031 at a dose of either 3.6 mg or 6 mg . Results The mean duration of grade 4 neutropenia in cycle 1 was comparable among the treatment groups ( 2.48 , 2.20 , and 2.05 days for filgrastim , DA-3031 3.6 mg and 6 mg , respectively ; P = 0.275 ) . No statistically significant differences were observed in the incidence of febrile neutropenia between the treatment groups ( 9.5 % , 15.0 % , and 5.0 % for filgrastim , DA-3031 3.6 mg and 6 mg , respectively ; P = 0.681 ) in cycle 1 . The incidences of adverse events attributable to G-CSF were similar among the treatment groups . Conclusions Fixed doses of 3.6 mg or 6 mg DA-3031 have an efficacy comparable to that of daily injections of filgrastim in ameliorating grade 4 neutropenia in patients receiving TAC chemotherapy BACKGROUND Mecapegfilgrastim ( code name HHPG-19 K ) is a biosimilar to pegylated recombinant human granulocyte-colony stimulating factor ( PEG-rhG-CSF ) . The efficacy and safety of mecapegfilgrastim , using a regimen of once-per-cycle injection of 100-μg/kg or a fixed 6-mg dose , were evaluated for the prophylactic therapy for neutropenia in patients with advanced non-small-cell lung cancer ( NSCLC ) who were treated with myelosuppressive chemotherapy . MATERIAL S AND METHODS Patients were r and omized ( 1:1:1 ) blindly to 3 treatment arms to receive a single injection of mecapegfilgrastim 100 μg/kg , a 6-mg fixed dose of mecapegfilgrastim , or saline ( control ) in cycle 1 . In cycles 2 to 4 following unblinding at the end of cycle 1 , patients in the control arm received daily injections of short-acting rhG-CSF at a dose of 5 μg/kg , whereas patients in the 2 mecapegfilgrastim arms continued the same treatment as in cycle 1 . All patients received 4 chemotherapy cycles of docetaxel combined with cisplatin or carboplatin every 21 days . The primary endpoint was the incidence of grade ≥ 3 neutropenia in cycle 1 . RESULTS A single dose of 100 μg/kg or a fixed 6-mg dose of mecapegfilgrastim per cycle effectively reduced chemotherapy-induced neutropenia and was comparable to daily rhG-CSF with regard to all efficacy endpoints , including incidence of grade ≥ 3 neutropenia , incidence of febrile neutropenia , duration of grade ≥ 3 neutropenia , and time to neutrophil recovery . No difference in efficacy parameters was observed between the 2-dose regimens of mecapegfilgrastim across all cycles . Mecapegfilgrastim was well-tolerated and was as safe as daily rhG-CSF . CONCLUSION Once-per-cycle injection of mecapegfilgrastim is as effective and safe as daily rhG-CSF for prophylaxis of chemotherapy-induced neutropenia in patients with NSCLC . Mecapegfilgrastim ( fixed 6-mg dose ) is recommended in clinical practice for its convenient dose management BACKGROUND Zarzio , a new recombinant human granulocyte colony-stimulating factor ( filgrastim ) , was evaluated in healthy volunteers and neutropenic patients in phase I and III studies . PATIENTS AND METHODS Healthy volunteers in r and omized , two-period crossover studies received single- and multiple-dose s.c . injections of 1 microg/kg ( n = 24 ) , 2.5 microg/kg ( n = 28 ) , 5 microg/kg ( n = 28 ) , or 10 microg/kg ( n = 40 ) , as well as single-dose i.v . infusions of 5 microg/kg ( n = 26 ) , of Zarzio or the reference product ( Neupogen ) . Filgrastim serum levels were monitored ; pharmacodynamic parameters were absolute neutrophil count ( all studies ) and CD34(+ ) cells ( multiple-dose studies ) . Supportive efficacy and safety data were obtained from an open phase III study in 170 breast cancer patients undergoing four cycles of doxorubicin and docetaxel ( Taxotere ) chemotherapy , receiving Zarzio ( 300 or 480 microg ) as primary prophylaxis of severe neutropenia . RESULTS The results of the studies in healthy volunteers confirm the comparability of the test and reference products with respect to their pharmacodynamics and pharmacokinetics . Confidence intervals were within the predefined equivalence boundaries . In the phase III study in breast cancer patients , the administration of Zarzio was efficacious and safe , triggering no immunogenicity . CONCLUSION The results of these studies demonstrate the biosimilarity of Zarzio with its reference product Neupogen This study was undertaken to describe the relationship between the occurrence and timing of neutropenic events and chemotherapy treatment in a community-based population of patients with cancer . The study included 2962 patients with breast , lung , colorectal , lymphoma , and ovarian cancers from a prospect i ve U.S. registry of patients initiating a new chemotherapy regimen . Detailed patient- , disease- , and treatment-related data , including toxicities , were captured at baseline , the beginning of each cycle , and each midcycle blood draw for up to 4 cycles of treatment . Primary outcomes included febrile neutropenia ( FN ) , severe neutropenia without fever/ infection , and relative dose intensity ( RDI ) . Thirty-seven percent of patients were aged 65 years or older , 43.5 % had an Eastern Cooperative Oncology Group performance status of 1 or greater , and 27 % had 1 or more comorbidities . Reductions in RDI to less than 85 % of st and ard in the first cycle were planned in 23.6 % of patients , whereas primary colony-stimulating factor prophylaxis was used in 18.2 % . In the first 3 cycles of treatment , 10.7 % of patients experienced FN , with most of these events ( 58.9 % ) occurring in the first cycle . This first-cycle pattern was consistently observed despite wide variations in event rates by tumor type , disease stage , chemotherapy regimen and dose , and patient characteristics . Despite frequent planned reductions from st and ard RDI , the incidence of FN remains high in community oncology practice in the United States . Improved methods of pretreatment assessment of patient risk factors for neutropenia are needed PROTECT-2 compared biosimilar LA-EP2006 with reference pegfilgrastim for the prevention of chemotherapy-induced neutropenia in 308 early-stage breast cancer patients receiving myelosuppressive chemotherapy . The two treatments were found to be therapeutically equivalent and comparable regarding efficacy and safety BACKGROUND A phase III study of filgrastim as an adjunct to combination chemotherapy in previously untreated patients with limited- or extensive-stage small-cell lung cancer was conducted . This final analysis explores baseline factors that might predict febrile neutropenia and also reports the results of 463 open-label filgrastim cycles that were delivered after patients ' initial episode of the primary endpoint , ie , febrile neutropenia . PATIENTS AND METHODS A total of 244 patients were r and omized to receive placebo or filgrastim in < /= 6 cycles of chemotherapy ( cyclophosphamide/doxorubicin/etoposide ) . RESULTS The cumulative percent of patients receiving filgrastim who experienced febrile neutropenia was approximately 50 % lower than those given placebo ( 38 % vs. 74 % , respectively ; P < 0.0001 ) . Significant treatment-related reductions were also seen in the incidence and duration of grade 4 neutropenia . Cycle 1 displayed the highest incidence of neutropenia with or without fever and the longest duration of neutropenia relative to later cycles . Patients crossing over to open-label filgrastim from their blinded treatment assignment displayed event rates similar to those in the blinded filgrastim group . Patients who experienced febrile neutropenia in cycle 1 were at a significantly higher risk for subsequent events compared with those who were event-free in cycle 1 . Women displayed a higher risk for febrile neutropenia than men , but no other baseline risk factors were detected . CONCLUSION Given the high rate of febrile neutropenia in cycle 1 and the higher risk for subsequent events in patients with a cycle 1 event , we conclude that growth factor administration starting in cycle 1 should be considered for patients receiving moderately to highly myelosuppressive chemotherapy regimens BACKGROUND There is a misconception that elderly cancer patients can not tolerate st and ard doses of chemotherapy because of the frequency and severity of myelosuppressive complications . The reactive use of colony-stimulating factors ( i.e. , in response to severe neutropenia ) commonly observed in this setting contributes to the frequency and severity of these complications . This study evaluated the incidence of febrile neutropenia and related events in elderly cancer patients receiving pegfilgrastim beginning with cycle 1 ( proactive ) in comparison with pegfilgrastim initiated after cycle 1 at the physician 's discretion ( reactive ) . METHODS Patients ( > or = 65 years of age ) with either solid tumors or non-Hodgkin 's lymphoma ( NHL ) were r and omly assigned to receive pegfilgrastim either proactively or reactively . The primary endpoint was the proportion of patients experiencing febrile neutropenia . RESULTS There were 852 patients enrolled ( median age , 72 years ) . Proactive pegfilgrastim use result ed in a significantly lower incidence of febrile neutropenia for both solid tumor and NHL patients compared with reactive use . Proactive pegfilgrastim use also led to fewer hospitalizations result ing from neutropenia and febrile neutropenia by approximately 50 % . Antibiotic use was lower for solid tumor patients receiving proactive pegfilgrastim and equivalent in the two NHL groups . CONCLUSIONS This is the largest , r and omized , prospect i ve trial evaluating growth factor support in typical elderly cancer patients . Proactive pegfilgrastim use effectively produced a lower incidence of febrile neutropenia and related events in elderly patients with either solid tumors or NHL receiving an array of mild to moderately neutropenic chemotherapy regimens . Pegfilgrastim should be used proactively in elderly cancer patients to support the optimal delivery of st and ard chemotherapy The primary objective of this prospect i ve , r and omized study was to compare the efficacy of a reduced regimen of only four doses of unpegylated filgrastim from day + 8 to + 11 per cycle with a st and ard once per cycle administration of pegylated filgrastim to maintain dose‐intensity of R‐CHOP‐14 ( rituximab , cyclophosphamide , doxorubicin , vincristine , prednisone given every 14 d ) in previously untreated elderly patients with diffuse large B‐cell lymphoma ( DLBCL ) . We included 51 patients ( median age 66 years , range 60–76 ) . Median dose intensity did not differ between the group of 24 patients receiving four doses of unpegylated filgrastim of each cycle ( 87·5 % ) and the group of 27 patients receiving pegylated filgrastim once per cycle on day 2 ( 89·4 % ) ( P = 0·9 ) . There was also no difference in the frequency of adverse events , such as episodes of neutropenic fever and unplanned hospitalizations . Patient characteristics that negatively influenced dose intensity were reduced performance status , advanced stage disease and poor‐risk International Prognostic Index , with Eastern Cooperative Oncology Group performance status ≥2 being the most significant factor . In conclusion , a limited support with 4 d of filgrastim appears to be equivalent to pegylated filgrastim administered once per cycle , and appears to be sufficient to maintain dose‐intensity of the R‐CHOP‐14 regimen in elderly patients with DLBCL without risk factors PURPOSE This two-arm , double-blind , r and omized trial was conducted to determine the effects of lenograstim , a glycosylated recombinant human granulocyte colony-stimulating factor ( rHu-G-CSF ) , on the hematologic tolerance of patients with sarcoma treated with mesna , doxorubicin , ifosfamide , and doxorubicin ( MAID ) chemotherapy . PATIENTS AND METHODS Forty-eight patients with metastatic or locally advanced soft tissue sarcoma were , following the first cycle of a combination with doxorubicin 60 mg/m2 , ifosfamide 7.5 g/m2 , and dacarbazine 900 mg/m2 , ifosfamide 7.5 g/m2 , and dacarbazine 900 mg/m2 given on days 1 to 3 , r and omized to receive either lenograstim 5 micrograms/kg/d by once-daily injection from day 4 to day 13 , or its vehicle . For subsequent cycles , 28 patients continued on the same chemotherapy and lenograstim was systematic ally given as prophylactic treatment in an open manner . RESULTS Following the first cycle of MAID , the duration of neutropenia was reduced in patients who received lenograstim as compared with those who received placebo , with a median duration of neutropenia ( < 0.5 x 10(9)/L neutrophils ) of 0 days ( range , 0 to 3 ) and 5 days ( range , 0 to 10 ) , respectively ( P < .001 ) . All patients who received lenograstim had recovered at least 1 x 10(9)/L neutrophils ( polymorphonuclear lymphocytes [ PMN ] ) on day 14 , compared with only one of 26 in the placebo group ( P < .001 ) . The median time to recover this neutrophil level was 12 days ( range , 10 to 13 ) and 17 days ( range , 14 to 21 ) , respectively ( P < .001 ) . Neutropenic fever occurred in five ( 23 % ) and 15 ( 58 % ) patients respectively ( P = .02 ) . Twenty-eight patients received at least two cycles ( median , four ) of MAID at the same dose . Toxicity remained constant across all treatment cycles . A progressive increase in thrombocytopenia was noted , with median platelet nadirs of 102 x 10(9)/L at cycle 2 and 19.5 x 10(9)/L at cycle 6 , but did not result in significant treatment modifications . Consequently , median relative dose-intensities remained greater than 0.95 for up to six consecutive MAID cycles . CONCLUSION Lenograstim significantly improved hematologic tolerance in patients treated with the MAID chemotherapy regimen and , therefore , allowed optimal adhesion to the theoretic doses planned for up to six cycles . Whether such an optimization in relative dose-intensity will result in an improvement of treatment efficacy remains to be determined PURPOSE Febrile neutropenia ( FN ) is a major complication of chemotherapy . Antibiotics as well as granulocyte colony-stimulating factor ( G-CSF ) are effective in preventing FN . This multicenter r and omized phase III trial determines whether the addition of G-CSF to antibiotic prophylaxis can further reduce the incidence of FN in patients with small-cell lung cancer ( SCLC ) at the risk of FN . PATIENTS AND METHODS Patients ( N = 175 ) were stratified for stage of disease , performance status , age , and prior chemotherapy treatment , and were r and omly assigned for treatment with cyclophosphamide , doxorubicin , and etoposide ( CDE ) , followed by prophylactic antibiotics alone ( ciprofloxacin and roxithromycin ) or by antibiotics in combination with G-CSF on days 4 to 13 . RESULTS In cycle 1 , 20 patients ( 24 % ) in the antibiotics group developed FN compared with nine patients ( 10 % ) in the antibiotics plus G-CSF group ( P = .01 ) . In cycles 2 to 5 , the incidences of FN were practically the same in both groups ( 17 % v 11 % ) . Only the treatment parameters ( odds ratio , 0.33 ; 95 % CI , 0.14 to 0.78 ) and age ( 1.067 per year ; 95 % CI , 1.013 to 1.0124 ) were related to the probability of FN in cycle 1 . CONCLUSION Primary G-CSF prophylaxis added to primary antibiotic prophylaxis is effective in reducing FN and infections in SCLC patients at the risk of FN with the first cycle of CDE chemotherapy . For patients with similar risk of FN , the combined use of prophylactic antibiotics plus G-CSF can be considered , specifically in the first cycle of chemotherapy PURPOSE To compare the efficacy and safety of recombinant human granulocyte colony-stimulating factor ( rHuG-CSF ) versus its inert vehicle in patients with unilateral nonmetastatic inflammatory breast cancer treated with fluorouracil , epirubicin , and cyclophosphamide high-dose ( FEC-HD ) neoadjuvant chemotherapy . PATIENTS AND METHODS One hundred twenty patients have been enrolled by nine French centers in this double-blind , parallel-group , vehicle-controlled study to compare at each cycle subcutaneous lenograstim ( 5 micrograms/kg/d ) with placebo given from day 6 to day 15 after the induction chemotherapy ( day 1 to day 4 , fluorouracil 750 mg/m2 continuous intravenous [ IV ] infusion ; day 2 to day 4 , epirubicin 35 mg/m2 and cyclophosphamide 400 mg/m2 both IV push ) . Four cycles were planned every 3 weeks before locoregional treatment . Patients with febrile neutropenia remained blinded for the subsequent cycles . RESULTS Lenograstim significantly reduced the duration of neutropenia at less than 0.5 x 10(9)/L and less than 1 x 10(9)/L to a median duration of 2 and 3 days , respectively , as compared with 5 and 7 days in the placebo group . This translated into a statistically significant reduced incidence of microbiologically documented infections , and a decreased need for rehospitalizations for infectious events and antibiotic use . Clinical objective tumor response rate observed after four cycles was 89.6 % and 93 % , respectively , in the placebo and treated groups . Mild transient bone and injection-site pain , myelemia , and hyperleukocytosis were the most frequently reported adverse events associated with lenograstim . CONCLUSION Lenograstim is safe and effective to reduce morbidity associated with FEC-HD neoadjuvant chemotherapy in inflammatory breast cancer . Response rate is not affected PURPOSE To explore the use of SD/01 ( a polyethylene glycol-conjugated filgrastim shown in pre clinical studies to have a prolonged half-life ) in patients with chemotherapy-induced neutropenia . PATIENTS AND METHODS Thirteen patients with non-small-cell lung cancer were r and omized to receive daily filgrastim ( 5 microg/kg/d ) or a single injection of SD/01 ( 30 , 100 , or 300 microg/kg ) 2 weeks before chemotherapy and again 24 hours after administration of carboplatin and paclitaxel . Pharmacodynamic , pharmacokinetic , and safety analyses were performed . RESULTS Peak serum concentrations of SD/01 and the duration of increased serum concentrations were dependent on the SD/01 dose . SD/01 concentrations remained increased longer in patients with chemotherapy-induced neutropenia . Prechemotherapy median absolute neutrophil counts ( ANCs ) in patients receiving SD/01 were increased in a dose-dependent fashion , with the duration of this effect also being dose dependent . After chemotherapy , median ANC nadirs were similar in the filgrastim cohort and the cohort receiving SD/01 30 microg/kg , with higher nadirs seen in the cohorts receiving SD/01 100 or 300 microg/kg . Dose-limiting toxicities were not noted . CD34(+ ) cells were mobilized in all cohorts . CONCLUSION A single dose of SD/01 increases the serum concentration of SD/01 for several days in a dose-dependent fashion and is not associated with significant toxicity . The effects of SD/01 on ANC and CD34(+ ) cell mobilization are comparable or greater than those achieved with daily filgrastim . The self-regulation of this molecule provides a potential therapeutic advantage in a variety of clinical setting s associated with neutropenia PURPOSE To investigate whether the relative dose-intensity of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) chemotherapy could be improved by prophylactic administration of granulocyte colony-stimulating factor ( G-CSF ) in elderly patients with aggressive non-Hodgkin 's lymphoma ( NHL ) . PATIENTS AND METHODS Patients aged 65 to 90 years ( median , 72 years ) with stage II to IV aggressive NHL were r and omly assigned to receive st and ard CHOP every 3 weeks or CHOP plus G-CSF every 3 weeks on days 2 to 11 of each cycle . RESULTS In 389 eligible patients , the relative dose intensities ( RDIs ) of cyclophosphamide ( median , 96.3 % v 93.9 % ; P = .01 ) and doxorubicin ( median , 95.4 % v 93.3 % ; P = .04 ) were higher in patients treated with CHOP plus G-CSF . The complete response rates were 55 % and 52 % for CHOP and CHOP plus G-CSF , respectively ( P = .63 ) . The actuarial overall survival at 5 years was 22 % with CHOP alone , compared with 24 % with CHOP plus G-CSF ( P = .76 ) , with a median follow-up of 33 months . Patients treated with CHOP plus G-CSF had an identical incidence of infections , with World Health Organization grade 3 to 4 ( 34 of 1,191 cycles v 36 of 1,195 cycles ) . Only the cumulative days with antibiotics were fewer with CHOP plus G-CSF ( median , 0 v 6 days ; P = .006 ) than with CHOP alone . The number of hospital admissions and the number of days in hospital were not different . CONCLUSION In elderly patients , G-CSF improved the RDI of CHOP , but this did not lead to a higher complete response rate or better overall survival . G-CSF did not prevent serious infections PURPOSE The primary objective was to assess the duration of grade 4 neutropenia ( neutrophil count < 0.5 x 10(9)/L ) after one cycle of chemotherapy with etoposide , methylprednisolone , cisplatin , and cytarabine in patients r and omly assigned to receive one dose of pegfilgrastim or daily filgrastim after chemotherapy . Febrile neutropenia , neutrophil profiles , time to neutrophil recovery , pharmacokinetics , and safety were also assessed . PATIENTS AND METHODS An open-label , r and omized , phase II study was design ed to compare the effects of a single subcutaneous injection of pegfilgrastim ( sustained- duration filgrastim ) 100 micro g/kg per chemotherapy cycle ( n = 33 ) with daily subcutaneous injections of filgrastim 5 micro g/kg ( n = 33 ) in patients receiving salvage chemotherapy for relapsed or refractory Hodgkin 's or non-Hodgkin 's lymphoma . RESULTS The incidence of grade 4 neutropenia in the pegfilgrastim and filgrastim groups was 69 % and 68 % , respectively . In addition , the mean duration of grade 4 neutropenia was similar in both groups ( 2.8 and 2.4 days , respectively ) . The results for the two groups were also not significantly different for febrile neutropenia , neutrophil profile , time to neutrophil recovery , or toxicity profile . A single subcutaneous injection of pegfilgrastim 100 micro g/kg produced a sustained serum concentration relative to daily subcutaneous injections of filgrastim . Filgrastim-treated patients received a median of 11 injections per cycle . CONCLUSION Pegfilgrastim was safe and well tolerated in this patient population . A single injection of pegfilgrastim per chemotherapy cycle provided neutrophil support with safety and efficacy similar to that provided by daily injections of filgrastim . Once-per-cycle administration of pegfilgrastim simplifies the management of neutropenia and may have important clinical benefits for patients and healthcare providers This study was design ed to test the hypothesis that administration of granulocyte colony-stimulating factor ( G-CSF ; filgrastim ) during induction chemotherapy with CHOP ( cyclophosphamide , vincristine , doxorubicin , prednisone ) or CNOP ( doxorubicin replaced with mitoxantrone ) in elderly patients with aggressive non-Hodgkin lymphoma ( NHL ) improves time to treatment failure ( TTF ) , complete remission ( CR ) rate , and overall survival ( OS ) . Furthermore , the efficacy of CHOP versus CNOP chemotherapy was compared . A total of 455 previously untreated patients older than 60 years with stages II to IV aggressive NHL were included in the analysis . Patients ( median age , 71 years ; range , 60 - 86 years ) were r and omized to receive CHOP ( doxorubicin 50 mg/m(2 ) ) or CNOP ( mitoxantrone 10 mg/m(2 ) ) with or without G-CSF ( 5 microg/kg from day 2 until day 10 - 14 of each cycle every 3 weeks ; 8 cycles ) . Forty-seven patients previously hospitalized for class I to II congestive heart failure were r and omized to receive CNOP with or without G-CSF ( not included in the CHOP versus CNOP analysis ) . The CR rates in the CHOP/CNOP plus G-CSF and CHOP/CNOP groups were the same , 52 % , and in the CHOP with or without G-CSF and CNOP with or without G-CSF groups , 60 % and 43 % ( P < .001 ) , respectively . No benefit of G-CSF in terms of TTF and OS could be shown ( P = .96 and P = .22 , respectively ) , whereas CHOP was superior to CNOP ( TTF/OS P < .001 ) . The incidences of severe granulocytopenia ( World Health Organization grade IV ) and granulocytopenic infections were higher in patients not receiving G-CSF . The cumulative proportion of patients receiving 90 % or more of allocated chemotherapy was higher ( P < .05 ) in patients receiving G-CSF . Concomitant G-CSF treatment did not improve CR rate , TTF , or OS . Patients receiving CHOP fared better than those given CNOP chemotherapy . The addition of G-CSF reduces the incidence of severe granulocytopenia and infections in elderly patients with aggressive NHL receiving CHOP or CNOP chemotherapy Background : Filgrastim was developed to treat chemotherapy-induced neutropenia . This phase III study was design ed to demonstrate bioequivalence of Amgen filgrastim and a biosimilar filgrastim developed by Hospira ( Study GCF071 ; sponsored by Hospira ) . Patients and Methods : Breast cancer patients suitable for treatment with doxorubicin and docetaxel in the neoadjuvant/adjuvant or first-line metastatic setting were enrolled at 37 European centers . Patients were r and omized ( 2:1 ) to receive Hospira filgrastim or Amgen filgrastim , after the end of chemotherapy . Filgrastim ( 5 µg/kg/day ) was administered under double-blind conditions . Primary endpoint to demonstrate bioequivalence was duration of severe neutropenia ( DSN ) in cycle 1 . Results : 184 patients were r and omized to Hospira filgrastim and 95 to Amgen filgrastim . Mean DSN in cycle 1 was similar with Hospira filgrastim ( 1.6 days ; n = 165 ) and Amgen filgrastim ( 1.3 days ; n = 85 ) , meeting predefined criteria for bioequivalence . Secondary endpoints supporting bioequivalence included mean time to absolute neutrophil count recovery and incidence of febrile neutropenia . The most common treatment-related adverse event with Hospira filgrastim was grade 1–2 bone pain . Conclusions : Hospira filgrastim and Amgen filgrastim are bioequivalent in efficacy with similar safety profiles . Hospira filgrastim may be useful for the prophylaxis of complications related to neutropenia caused by chemotherapy Balugrastim is a once-per-cycle , fixed-dose recombinant protein comprising human serum albumin and granulocyte colony-stimulating factor under development for prevention of severe neutropenia in cancer patients receiving myelosuppressive chemotherapy . This phase II , multicenter , active-controlled , dose-finding pilot study evaluated balugrastim safety and efficacy versus pegfilgrastim in breast cancer patients scheduled to receive myelosuppressive chemotherapy and investigated two doses with similar efficacy to pegfilgrastim for a subsequent phase III study . Patients received four cycles of doxorubicin/docetaxel chemotherapy and with each successive cycle were r and omized sequentially to escalating doses of balugrastim [ 30 ( n = 11 ) , 40 ( n = 21 ) , or 50 mg ( n = 20 ) ] or a fixed dose of pegfilgrastim [ 6 mg ( n = 26 ) ] post-chemotherapy . Balugrastim doses were escalated as planned . The incidence of adverse events was similar among the balugrastim groups and between all balugrastim doses and pegfilgrastim . The most frequently reported adverse events were neutropenia , alopecia , and nausea . During cycle 1 , severe neutropenia ( absolute neutrophil count of < 0.5 × 109/L ) occurred in 40 , 67 , and 50 % and febrile neutropenia occurred in 20.0 , 9.5 , and 10.0 % of patients receiving balugrastim 30 , 40 , and 50 mg , respectively ; in patients receiving pegfilgrastim , 48 % experienced severe neutropenia and 8 % experienced febrile neutropenia . Duration of severe neutropenia ( DSN ) for each treatment group was 0.9 , 1.6 , 1.1 , and 0.9 days , respectively . In the remaining three chemotherapy cycles , DSN was ≤1 day across all treatment groups . Balugrastim 50 mg was comparable to pegfilgrastim in terms of safety and overall efficacy in breast cancer patients receiving myelosuppressive chemotherapy OBJECTIVE To explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor ( PEG-rhG-CSF ) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer ( NSCLC ) , and to provide the basis for clinical application . METHODS According to the principle of open-label , r and omized , parallel-group controlled clinical trial , all patients were r and omized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg , PEG-rhG-CSF 6 mg , or rhG-CSF 5 μg/kg , respectively . The patients with breast cancer received two chemotherapy cycles , and the NSCLC patients received 1 - 2 cycles of chemotherapy according to their condition . All patients were treated with the combination chemotherapy of TAC ( docetaxel+ epirubicin+ cyclophosphamide ) or TA ( docetaxel+ epirubicin ) , or the chemotherapy of docetaxel combined with carboplatin , with a 21 day cycle . RESULTS The duration of grade 3 - 4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group ( P>0.05 for all ) . The incidence rate of grade 3 - 4 neutropenia in the PEG-rhG-CSF 100 μg/kg group , PEG-rhG-CSF 6 mg group , and G-CSF 5 μg/kg group were 69.7 % , 68.4 % , and 69.5 % , respectively , with a non-significant difference among the three groups ( P=0.963 ) . The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group , PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1 % , 6.4 % , and 5.5 % , respectively , showing no significant difference among them ( P=0.935 ) . The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group , PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7 % , 4.1 % , and 5.5 % , respectively , showing a non-significant difference among them ( P=0.581 ) . CONCLUSIONS In patients with breast cancer and non-small cell lung cancer ( NSCLC ) undergoing TAC/TA chemotherapy , a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions . Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d , a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia The purpose of this study was to , assess the efficacy of glycosylated recombinant human granulocyte colony-stimulating factor ( lenograstim ) in the prevention of neutropenia and infection in patients receiving dose-intensive chemotherapy for non-Hodgkin 's lymphoma ( NHL ) . A second objective was to determine clinical predicators of delay to cytotoxic chemotherapy administration . One hundred-sixty two patients with intermediate- or high- grade NHL and at least one poor prognostic factor received a total of 4 cycles of the LNH-84-regimen every 2 weeks , with an open r and omization to treatment with anthracyclines . Patients were r and omized to receive subcutaneous lenograstim 5 micrograms/kg/day ( n = 82 ) or placebo ( n = 80 ) from day 6 to day 13 of each cycle . The incidence of severe neutropenia ( absolute neutrophil count ( ANC ) < 0.5 x 10(9)/L ) was reduced in the lenograstim group compared with placebo ( 52 % vs 75 % ) . A significant reduction ( p < 0.001 ) in the median duration of ANC < 0.5 x 10(9)/L was also observed in patients treated with lenograstim during each cycle of chemotherapy ( 0 - 1 day vs 2 - 4 days in placebo recipients ) . Fever occurred in 66 patients in each treatment group . Thirty-four percent of placebo recipients had documented infections during ANC < 1.0 x 10(9)/L compared with 18.5 % of lenograstim-treated patients ( p < 0.05 ) . Infections of > or = 2 severity were significantly less frequent ( p = 0.001 ) among lenograstim recipients compared with placebo ( 25 vs 49 ) . The most common adverse events among lenograstim recipients were headache , mild bone pain and injection site reactions . Although lenograstim significantly increased ( p = 0.0001 ) relative dose intensity compared with placebo ( 93 % vs 80 % ) , no difference in CR rate ( 67 % vs 71 % ) or 3-year survival ( 63 % vs 55 % ) was observed . The results of this study suggest that patients treated with a chemotherapy regimen that induces severe neutropenia can benefit from treatment with lenograstim . Furthermore , lenograstim permits treatment to be delivered at full dose intensity at 2 week intervals , even in patients with bone marrow involvement , and may permit further dose escalation of the chemotherapeutic regimen used Background Chemotherapy-induced neutropenia is a common result of myelosuppressive chemotherapy treatment . Infections such as febrile neutropenia ( FN ) are sensitive to the duration of neutropenia as well as the depth of absolute neutrophil count ( ANC ) at nadir . Filgrastim , a granulocyte colony stimulating factor ( G-CSF ) , can stimulate the function of mature neutrophils . Pegfilgrastim , a long-acting form of filgrastim , has been shown to reduce FN to a greater extent compared to filgrastim . G-CSF agents have been recommended for prophylactic administration with chemotherapy . Apotex developed a proposed pegfilgrastim biosimilar . This study was conducted to confirm that no clinical ly meaningful efficacy or safety differences exist between Apotex ’s proposed biosimilar and its reference product . Methods 589 breast cancer patients were r and omized and dosed with the proposed pegfilgrastim biosimilar , US-licensed pegfilgrastim reference product , or EU-approved pegfilgrastim reference product . The primary endpoint assessed was the duration of severe neutropenia ( DSN ) and secondary endpoints included rate of FN and ANC nadir . Results Data showed that the mean DSN , the primary endpoint measured , was comparable across all three treatments . The As Treated arm had a 95 % confidence interval within the equivalence range for the proposed pegfilgrastim biosimilar with the US-licensed and EU-approved pegfilgrastim reference products . Secondary endpoints , which included depth and peak of ANC nadir , time to ANC recovery post-nadir and rates of FN , also showed similarity between the three different treatment groups . The adverse event incidence was similar across treatment arms and there were no unexpected safety events . Conclusions Overall , these results show that the proposed pegfilgrastim biosimilar is similar to Amgen ’s US-licensed and EU-approved pegfilgrastim reference products with regard to the clinical efficacy and safety endpoints assessed . Trial registration EMA : European Union Clinical Trials Register : ( https://www . clinical trialsregister.eu/ctr- search / search ? query = eudract_number:2011 - 002678 - 21 ) Eudract # 2011 - 002678 - 21 Registered : Background : Recombinant granulocyte colony-stimulating factors such as Neupogen are used to treat chemotherapy-induced neutropenia . The aim of the study was to show that a new granulocyte colony-stimulating factor , XM02 , is as safe and effective as Neupogen in the treatment of chemotherapy-induced neutropenia in patients with small cell or non-small cell lung cancer . Patients and methods : A total of 240 patients receiving platinum-based chemotherapy were r and omized in cycle 1 to treatment with daily injections ( subcutaneous 5 & mgr;g/kg/d ) of XM02 ( n = 160 ) or Filgrastim Neupogen ( n = 80 ) for at least 5 days and a maximum of 14 days . In subsequent cycles , all patients received XM02 . Results : The mean duration of severe neutropenia was 0.5 and 0.3 days in cycle 1 for XM02 and Filgrastim , respectively . In the analysis of covariance for duration of severe neutropenia in cycle 1 , the estimated treatment difference “ XM02 minus Filgrastim ” was 0.157 days , with 95 % confidence level ( −0.114 days , 0.428 days ) , which was included in the prespecified equivalence range ( −1 , 1 ) . There was no statistically significant difference of the end point incidence of febrile neutropenia in cycle 1 between XM02 and Filgrastim ( p = 0.2347 ) . The adverse event profile was similar between XM02 and Filgrastim . Conclusion : XM02 demonstrated similar efficacy and safety profile as the reference medication Filgrastim in cycle 1 . In conclusion , treatment with XM02 is beneficial in ameliorating severe neutropenia and febrile neutropenia in lung cancer patients receiving myelosuppressive chemotherapy . XM02 is safe and well tolerated in the doses applied in this study BACKGROUND Recombinant granulocyte colony-stimulating factors ( G-CSFs ) reduce the incidence and duration of chemotherapy-induced neutropenia and febrile neutropenia when given as adjunct therapy to patients receiving myelosuppressive chemotherapy . Balugrastim is a long-acting G-CSF composed of a genetic fusion between recombinant human serum albumin and G-CSF . We compared the efficacy and safety of balugrastim and pegfilgrastim , a long-acting pegylated recombinant G-CSF , in patients with breast cancer who were scheduled to receive chemotherapy . PATIENTS AND METHODS In this double-blind r and omized phase III trial , patients with ≥ 1.5 × 10(9 ) neutrophils/L were r and omly assigned to subcutaneous injections of balugrastim 40 mg ( n = 153 ) or pegfilgrastim 6 mg ( n = 151 ) . The primary efficacy end point was the duration of severe neutropenia ( DSN ) ( days with an absolute neutrophil count [ ANC ] < 0.5 × 10(9 ) cells/L ) during cycle 1 . Efficacy analyses were performed in the per- protocol ( PP ) population . In a separate open-label single-arm study , newly recruited patients ( n = 77 ) received balugrastim 40 mg and were included in the safety analysis . RESULTS The mean DSN in cycle 1 was 1.1 days in the balugrastim group and 1.0 days in the pegfilgrastim group ( 95 % confidence interval [ CI ] , -0.13 - 0.37 ) . Two and 4 patients , respectively , had febrile neutropenia during cycle 1 . Twenty percent of patients in the balugrastim group and 19 % in the pegfilgrastim group had adverse events ( AEs ) considered to be related to study medication ; 3.9 % and 4.7 % of patients , respectively , experienced serious AEs . CONCLUSIONS This study demonstrates the comparable safety and efficacy profile of balugrastim and pegfilgrastim and the noninferiority of balugrastim for reduction in DSN . There were no unexpected safety events |
1,605 | 21,669,371 | Sensitivity analyses demonstrated that higher WTP threshold , younger age , earlier stage at diagnosis , or reduced G-CSF prices result in G-CSF prophylaxis being cost-effective at lower baseline FN risk levels .
CONCLUSION Pegfilgrastim was the most cost-effective G-CSF .
The most cost-effective strategy ( primary or secondary prophylaxis ) was dependent on the FN risk level for an individual patient , patient age and stage at diagnosis , and G-CSF price | OBJECTIVE We report a cost-effectiveness evaluation of granulocyte colony-stimulating factors ( G-CSFs ) for the prevention of febrile neutropenia ( FN ) after chemotherapy in the United Kingdom ( UK ) . | BACKGROUND The aim of the study was to analyse the toxicity and health related quality of life ( HRQoL ) of breast cancer patients treated with FAC ( 5-fluorouracil , doxorubicin , cyclophosphamide ) and TAC ( docetaxel , doxorubicin , cyclophosphamide ) with and without primary prophylactic G-CSF ( PPG ) . PATIENTS AND METHODS This was a phase III study to compare FAC and TAC as adjuvant treatment of high-risk node-negative breast cancer patients . After the entry of the first 237 patients , the protocol was amended to include PPG in the TAC arm due to the high incidence of febrile neutropenia . A total of 1047 evaluable patients from 49 centres in Spain , two in Pol and and four in Germany were included in the trial . Side-effects and the scores of the EORTC QLQ-C30 and QLQ BR-23 question naires were compared in the three groups ( FAC , TAC pre-amendment and TAC post-amendment ) . RESULTS The addition of PPG to TAC significantly reduced the incidence of neutropenic fever , grade 2 - 4 anaemia , asthenia , anorexia , nail disorders , stomatitis , myalgia and dysgeusia . Patient QoL decreased during chemotherapy , more with TAC than FAC , but returned to baseline values afterwards . The addition of PPG to TAC significantly reduced the percentage of patients with clinical ly relevant Global Health Status deterioration ( 10 or more points over baseline value ) at the end of chemotherapy ( 64 % versus 46 % , P<0.03 ) . CONCLUSIONS The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects . The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG , particularly in the final part of chemotherapy treatment BACKGROUND Neutropenia is common in patients receiving myelotoxic chemotherapy . Pegfilgrastim , a sustained- duration filgrastim is a once-per-cycle therapy for prophylactic neutrophil support . PATIENTS AND METHODS Women , treated with four cycles of doxorubicin/docetaxel chemotherapy every 21 days , received pegfilgrastim or filgrastim 24 h after chemotherapy as a single subcutaneous injection per chemotherapy cycle ( pegfilgrastim 30 , 60 or 100 microg/kg ) or daily subcutaneous injections ( filgrastim 5 microg/kg/day ) . Safety , efficacy and pharmacokinetics were analyzed . RESULTS The incidence of grade 4 neutropenia in cycle 1 was 95 , 90 and 74 % , in patients who received pegfilgrastim 30 , 60 and 100 microg/kg , respectively , and 76 % in patients who received filgrastim . Mean duration of grade 4 neutropenia in cycle 1 was 2.7,2 and 1.3 days for doses of pegfilgrastim , and 1.6 days for filgrastim . The pharmacokinetics of pegfilgrastim were non-linear and dependent on both dose and neutrophil count . Pegfilgrastim serum concentration was sustained until the neutrophil nadir occurred then declined rapidly as neutrophils started to recover , consistent with a self-regulating neutrophil-mediated clearance mechanism . The safety profiles of pegfilgrastim and filgrastim were similar . CONCLUSIONS A single subcutaneous injection of pegfilgrastim 100 microg/kg provided neutrophil support and a safety profile comparable to daily subcutaneous injections of filgrastim during multiple chemotherapy cycles 632 Background : Following the BCIRG 001 , PACS 01 and HERA trials , this r and omised , multicentre , open-label , Phase III trial was design ed to demonstrate the benefit of concomitant docetaxel and epirubicin versus anthracyclines , and evaluate the use of sequential trastuzumab . METHODS Patients ( pts ) with localised , resectable , unilateral breast cancer who met the following criteria were eligible : age < 65 years , ≥1 positive node , M0 , adequate heart and organ functions . Pts were r and omised to receive either 6 cycles of 5-fluorouracil-epirubicin-cyclophosphamide ( FEC100 : F and C , 500 mg/m2 , E 100 mg/m2 ) ( Arm A ) or epirubicin-docetaxel ( ET75 : E 75 mg/m2 , T 75 mg/m2 ) ( Arm B ) . Primary prophylaxis with G-CSF was not planned . Radiotherapy was m and atory after conservative surgery and tamoxifen was required in pts with hormone receptor-positive tumours . Pts with HER2-positive disease were then further r and omised to observation only or to 1 year of trastuzumab monotherapy ( 6 mg/kg iv every 3 weeks ) . In HER2-positive pts receiving trastuzumab , left ventricular ejection fraction ( LVEF ) was determined at Cycles 2 , 4 , 8 , 13 , 18 and after 2 years . Otherwise , LVEF was determined at baseline and at 1 year post-surgery . RESULTS Of the 3010 pts recruited ( 2622 evaluable for safety to date ) , 1518 received FEC100 and 1492 received ET75 after the first r and omisation . Haematologic toxicity was the most frequent toxicity in both arms . Grade 3 - 4 toxicities were similar for Arms A and B , except febrile neutropenia ( 10.3 % and 31.4 % , respectively ) and nausea/vomiting ( 13.2 % and 7.5 % , respectively ) . Grade 2 clinical cardiac toxicity ( decreased LVEF ) was observed in 4 pts in Arm A and 5 in Arm B , with median LVEF scores of 63 % in both arms at the end of chemotherapy . HER2-positive pts ( n=500 ) were then r and omised to either receive trastuzumab ( n=259 ) or observation only ( n=241 ) . CONCLUSIONS These preliminary safety data indicate that FEC100 and ET75 were both well tolerated , with acceptable cardiac safety values . The trial is ongoing and further analysis regarding the use of trastuzumab in this setting will be presented . [ Table : see text ] BACKGROUND TAC ( docetaxel/doxorubicin/cyclophosphamide ) is associated with high incidences of grade 4 neutropenia and febrile neutropenia ( FN ) . This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC . PATIENTS AND METHODS Patients with stage T2-T4 primary breast cancer were scheduled to receive 6 - 8 cycles of TAC . Primary prophylaxis was : ciprofloxacin 500 mg orally twice daily on days 5 - 14 ( n = 253 patients ; 1478 cycles ) , daily granulocyte colony-stimulating factor ( G-CSF ) ( filgrastim 5 microg/kg/day or lenograstim 150 microg/m(2)/day ) on days 5 - 10 ( n = 377 ; 2400 cycles ) , pegfilgrastim 6 mg on day 2 ( n = 305 ; 1930 cycles ) , or pegfilgrastim plus ciprofloxacin ( n = 321 ; 1890 cycles ) . RESULTS Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN ( 5 % and 7 % versus 18 % and 22 % of patients ; all P < 0.001 ) , grade 4 neutropenia , and leukopenia . Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN ( P < 0.01 versus pegfilgrastim alone ) and fatal neutropenic events . CONCLUSION Ciprofloxacin alone , or daily G-CSF from day 5 - 10 ( as in common practice ) , provided suboptimal protection against FN and related toxic effects in patients receiving TAC . Pegfilgrastim was significantly more effective in this setting , especially if given with ciprofloxacin Background Recombinant granulocyte colony-stimulating factors ( G-CSFs ) such as Filgrastim are used to treat chemotherapy-induced neutropenia . We investigated a new G-CSF , XM02 , and compared it to Neupogen ™ after myelotoxic chemotherapy in breast cancer ( BC ) patients . Methods A total of 348 patients with BC receiving docetaxel/doxorubicin chemotherapy were r and omised to treatment with daily injections ( subcutaneous 5 μg/kg/day ) for at least 5 days and a maximum of 14 days in each cycle of XM02 ( n = 140 ) , Neupogen ™ ( n = 136 ) or placebo ( n = 72 ) . The primary endpoint was the duration of severe neutropenia ( DSN ) in cycle 1 . Results The mean DSN in cycle 1 was 1.1 , 1.1 , and 3.9 days in the XM02 , Neupogen ™ , and placebo group , respectively . Superiority of XM02 over placebo and equivalence of XM02 with Neupogen ™ could be demonstrated . Toxicities were similar between XM02 and Neupogen ™ . Conclusion XM02 was superior to placebo and equivalent to Neupogen ™ in reducing DSN after myelotoxic chemotherapy . Trial Registration Current Controlled Trials IS RCT PURPOSE We evaluated the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia associated with docetaxel in breast cancer patients . PATIENTS AND METHODS Patients were r and omly assigned to either placebo or pegfilgrastim 6 mg subcutaneously on day 2 of each 21-day chemotherapy cycle of 100 mg/m(2 ) docetaxel . The primary end point was the percentage of patients developing febrile neutropenia ( defined as body temperature > /= 38.2 degrees C and neutrophil count < 0.5 x 10(9)/L on the same day of the fever or the day after ) . Secondary end points were incidence of hospitalizations associated with a diagnosis of febrile neutropenia , intravenous ( IV ) anti-infectives required for febrile neutropenia , and the ability to maintain planned chemotherapy dose on time . Patients with febrile neutropenia were converted to open-label pegfilgrastim in subsequent cycles . RESULTS Nine hundred twenty-eight patients received placebo ( n = 465 ) or pegfilgrastim ( n = 463 ) . Patients receiving pegfilgrastim , compared with patients receiving placebo , had a lower incidence of febrile neutropenia ( 1 % v 17 % , respectively ; P < .001 ) , febrile neutropenia-related hospitalization ( 1 % v 14 % , respectively ; P < .001 ) , and use of IV anti-infectives ( 2 % v 10 % , respectively ; P < .001 ) . The percentage of patients receiving the planned dose on time was similar between patients receiving pegfilgrastim and patients who initially received placebo ( 80 % and 78 % , respectively ) , as would be expected of the study design . Pegfilgrastim was generally well tolerated and safe , and the adverse events reported were typical of this patient population . CONCLUSION First and subsequent cycle use of pegfilgrastim with a moderately myelosuppressive chemotherapy regimen markedly reduced febrile neutropenia , febrile neutropenia-related hospitalizations , and IV anti-infective use PURPOSE This multicenter , r and omized , double-blind , active-control study was design ed to determine whether a single subcutaneous injection of pegfilgrastim ( SD/01 , sustained- duration filgrastim ; 100 microg/kg ) is as safe and effective as daily filgrastim ( 5 microg/kg/d ) for reducing neutropenia in patients who received four cycles of myelosuppressive chemotherapy . PATIENTS AND METHODS Sixty-two centers enrolled 310 patients who received chemotherapy with docetaxel 75 mg/m(2 ) and doxorubicin 60 mg/m(2 ) on day 1 of each cycle for a maximum of four cycles . Patients were r and omized to receive on day 2 either a single subcutaneous injection of pegfilgrastim 100 microg/kg per chemotherapy cycle ( 154 patients ) or daily subcutaneous injections of filgrastim 5 microg/kg/d ( 156 patients ) . Absolute neutrophil count ( ANC ) , duration of grade 4 neutropenia , and safety parameters were monitored . RESULTS One dose of pegfilgrastim per chemotherapy cycle was comparable to daily subcutaneous injections of filgrastim with regard to all efficacy end points , including the duration of severe neutropenia and the depth of ANC nadir in all cycles . Febrile neutropenia across all cycles occurred less often in patients who received pegfilgrastim . The difference in the mean duration of severe neutropenia between the pegfilgrastim and filgrastim treatment groups was less than 1 day . Pegfilgrastim was safe and well tolerated , and it was similar to filgrastim . Adverse event profiles in the pegfilgrastim and filgrastim groups were similar . CONCLUSION A single injection of pegfilgrastim 100 microg/kg per cycle was as safe and effective as daily injections of filgrastim 5 microg/kg/d in reducing neutropenia and its complications in patients who received four cycles of doxorubicin 60 mg/m(2 ) and docetaxel 75 mg/m(2 ) Abstract Objective : To measure the health of a representative sample of the population of the United Kingdom by using the EuroQoL EQ-5D question naire . Design : Stratified r and om sample representative of the general population aged 18 and over and living in the community . Setting : United Kingdom . Subjects : 3395 people resident in the United Kingdom . Main outcome measures : Average values for mobility , self care , usual activities , pain or discomfort , and anxiety or depression . Results : One in three respondents reported problems with pain or discomfort . There were differences in the perception of health according to the respondent 's age , social class , education , housing tenure , economic position , and smoking behaviour . Conclusions : The EQ-5D question naire is a practical way of measuring the health of a population and of detecting differences in subgroups of the population . Key messages Measurement of health outcome requires the observation of states of health Patients ' involvement in recording and assessing their own state of health is a major element in the process of evaluating the impact of health care The EuroQoL EQ-5D question naire highlights variations in states of health which are consistent with previously published results High degrees of pain are reported in the general population . A category for pain is absent and thus undetected in the survey of disability by the Office of Population Censuses and Pegfilgrastim is composed of the protein filgrastim to which a 20-kDa polyethylene glycol ( PEG ) is covalently bound at the N-terminal residue result ing in decreased renal clearance and increased plasma half-life compared with filgrastim . This open-label , r and omized , phase 2 study compared two doses of single administration pegfilgrastim ( 60 and 100 μg/kg ) with daily doses of filgrastim ( 5 μg/kg/day ) or no cytokine treatment after st and ard CHOP ( cyclophosphamide , doxorubicin , vincristine and prednisolone ) chemotherapy for non-Hodgkin 's lymphoma in 50 elderly patients . The primary endpoint was the duration of grade 4 ( severe ) neutropenia ( absolute neutrophil count < 0.5 × 109/l ) in cycle 1 . Duration of grade 4 neutropenia in cycle 1 was 2.2 ( SD 1.2 ) , 1.5 ( SD 1.1 ) , 0.8 ( 1.2 ) and 5.0 ( 2.0 ) days for patients who received pegfilgrastim 60 μg/kg , pegfilgrastim 100 μg/kg , filgrastim 5 μg/kg and no cytokine , respectively . The baseline characteristics of the pegfilgrastim and filgrastim groups were imbalanced with increased bone-marrow involvement and prior therapy in the former . When the treatment groups were balanced for these risk factors , duration of grade 4 neutropenia was comparable with 2.0 and 3.0 vs. 0.6 and 0.5 days for pegfilgrastim 100 μg/kg and filgrastim patients with and without these risk factors , respectively . The incidence of febrile neutropenia ( defined as ANC < 0:5 × 109/l and temperature > 38.2 ° C ) was low ( 10 % of patients ) . Pegfilgrastim was well tolerated with a safety profile similar to daily filgrastim . Once per chemotherapy cycle administration of pegfilgrastim was comparable to filgrastim in this clinical setting This r and omized phase 2 study explored the feasibility of delivering four to six cycles of the dose-intensified regimen FEC-100 ( 5-fluorouracil , epirubicin , and cyclophosphamide ) to elderly patients with stage II-III breast cancer , using pegfilgrastim for neutrophil support . Sixty patients aged 65 - 77 years received single 6 mg doses of pegfilgrastim on day 2 of FEC-100 , either as primary prophylaxis ( all cycles : PP ) , or as secondary prophylaxis ( all cycles following a neutropenic event : SP ) . Neutropenic events ( a composite endpoint that included grade 3 neutropenia+fever , grade 4 neutropenia , infectious complication requiring systemic anti-infectives and chemotherapy dose delay/reduction ) occurred in 24/30 ( 80 % ) of the PP and 21/29 ( 72 % ) of the SP group in the first cycle . Most patients received all chemotherapy cycles at full dose on schedule ( 26/30 [ 87 % ] PP ; 20/29 [ 69 % ] SP ) . These data indicate that delivery of FEC-100 is feasible with pegfilgrastim support in elderly breast cancer patients 4072 Background : Survival in advanced CRC is prolonged by adding oxaliplatin ( Ox ) and /or irinotecan ( Iri ) to Q2W 5-fluorouracil/leucovorin ( 5FU/LV ) . Combination therapy , however , has a higher incidence of febrile neutropenia ( FN ) and related toxicities . This study evaluated pegfilgrastim dosing on day 4 of Q2W regimens in CRC . Here we present long-term follow-up of these pts . METHODS Advanced CRC pts were r and omized ( 1:1 ) to pegfilgrastim 6 mg or placebo , which was stratified by CT regimen received : FOIL , FOLFOX , or FOLFIRI . We previously reported grade 3/4 neutropenia ( primary endpoint ) in 43 % placebo and 13 % pegfilgrastim pts in the 4-cycle treatment phase ( odds ratio = 0.19 , 95 % CI : 0.10 - 0.37 ; p < 0.0001 ) . After end of treatment , pts were followed long term for ≤ 2 years ( inclusive of ≤ 8 additional cycles ) for serious adverse events ( SAEs ) , overall survival ( OS ) , and progression-free survival ( PFS ) . Median follow-up time was 519 days . Kaplan-Meier methods estimated OS and PFS from study day 1 . The study was not powered to detect PFS or OS differences between treatment groups . RESULTS Of 241 pts analyzed ( 123 pegfilgrastim , 118 placebo ) , 49 % received FOLFOX , 26 % FOLFIRI , and 25 % FOIL . In the treatment period , 8 % placebo and 2 % pegfilgrastim pts had grade 3/4 FN ( Table ) . Pegfilgrastim was well tolerated with no dose delays attributed to leukocytosis . Pegfilgrastim and placebo had similar PFS and OS ( Table ) . No SAEs related to study drug were reported in the follow-up period . CONCLUSIONS In this r and omized , placebo-controlled study , pegfilgrastim significantly lowered neutropenic risk . Bone pain incidence in this CRC population was lower than in breast cancer pts treated with a taxane ( Vogel J Clin Oncol 2005 ) ; the incidence in pegfilgrastim pts was modestly increased over placebo . Leukocytosis was not a concern despite the 11-day dosing interval . Long-term results suggest similar PFS and OS in the pegfilgrastim and placebo pts in this CRC study . [ Table : see text ] [ Table : see text ] BACKGROUND There is a misconception that elderly cancer patients can not tolerate st and ard doses of chemotherapy because of the frequency and severity of myelosuppressive complications . The reactive use of colony-stimulating factors ( i.e. , in response to severe neutropenia ) commonly observed in this setting contributes to the frequency and severity of these complications . This study evaluated the incidence of febrile neutropenia and related events in elderly cancer patients receiving pegfilgrastim beginning with cycle 1 ( proactive ) in comparison with pegfilgrastim initiated after cycle 1 at the physician 's discretion ( reactive ) . METHODS Patients ( > or = 65 years of age ) with either solid tumors or non-Hodgkin 's lymphoma ( NHL ) were r and omly assigned to receive pegfilgrastim either proactively or reactively . The primary endpoint was the proportion of patients experiencing febrile neutropenia . RESULTS There were 852 patients enrolled ( median age , 72 years ) . Proactive pegfilgrastim use result ed in a significantly lower incidence of febrile neutropenia for both solid tumor and NHL patients compared with reactive use . Proactive pegfilgrastim use also led to fewer hospitalizations result ing from neutropenia and febrile neutropenia by approximately 50 % . Antibiotic use was lower for solid tumor patients receiving proactive pegfilgrastim and equivalent in the two NHL groups . CONCLUSIONS This is the largest , r and omized , prospect i ve trial evaluating growth factor support in typical elderly cancer patients . Proactive pegfilgrastim use effectively produced a lower incidence of febrile neutropenia and related events in elderly patients with either solid tumors or NHL receiving an array of mild to moderately neutropenic chemotherapy regimens . Pegfilgrastim should be used proactively in elderly cancer patients to support the optimal delivery of st and ard chemotherapy PURPOSE Febrile neutropenia ( FN ) is a major complication of chemotherapy . Antibiotics as well as granulocyte colony-stimulating factor ( G-CSF ) are effective in preventing FN . This multicenter r and omized phase III trial determines whether the addition of G-CSF to antibiotic prophylaxis can further reduce the incidence of FN in patients with small-cell lung cancer ( SCLC ) at the risk of FN . PATIENTS AND METHODS Patients ( N = 175 ) were stratified for stage of disease , performance status , age , and prior chemotherapy treatment , and were r and omly assigned for treatment with cyclophosphamide , doxorubicin , and etoposide ( CDE ) , followed by prophylactic antibiotics alone ( ciprofloxacin and roxithromycin ) or by antibiotics in combination with G-CSF on days 4 to 13 . RESULTS In cycle 1 , 20 patients ( 24 % ) in the antibiotics group developed FN compared with nine patients ( 10 % ) in the antibiotics plus G-CSF group ( P = .01 ) . In cycles 2 to 5 , the incidences of FN were practically the same in both groups ( 17 % v 11 % ) . Only the treatment parameters ( odds ratio , 0.33 ; 95 % CI , 0.14 to 0.78 ) and age ( 1.067 per year ; 95 % CI , 1.013 to 1.0124 ) were related to the probability of FN in cycle 1 . CONCLUSION Primary G-CSF prophylaxis added to primary antibiotic prophylaxis is effective in reducing FN and infections in SCLC patients at the risk of FN with the first cycle of CDE chemotherapy . For patients with similar risk of FN , the combined use of prophylactic antibiotics plus G-CSF can be considered , specifically in the first cycle of chemotherapy |
1,606 | 24,770,582 | Conclusion Combination of sorafenib and TACE showed survival and clinical benefits in patients with HCC , though enhanced morbidity | Abstract Background and aim Combination therapy of sorafenib and transarterial chemoembolization ( TACE ) showed benefits for hepatocellular carcinoma ( HCC ) .
This systematic review aims for evaluation of efficacy and safety between sorafenib plus TACE and TACE alone for HCC . | PURPOSE To evaluate safety and efficacy of combined transarterial chemoembolization ( TACE ) with doxorubicin-eluting beads ( DEB ) and sorafenib in patients with advanced hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS A prospect i ve single-center phase II study was undertaken involving patients with unresectable HCC . The protocol involved sorafenib 400 mg twice per day combined with DEB-TACE . Safety and response were assessed . Results DEB-TACE in combination with sorafenib was successfully administered in 35 patients : mean age , 63 years ; Child 's A , 89 % ; Barcelona Clinic Liver Cancer stage C , 64 % ; Eastern Cooperative Oncology Group performance status of 0 and 1 , 46 % and 54 % , respectively ; and mean index tumor size , 7.7 cm ( st and ard deviation , ± 4.2 cm ) . Patients underwent 128 cycles of therapy ( sorafenib plus DEB-TACE , 60 cycles ; sorafenib alone , 68 cycles ) . Median number of cycles per patient was two ( range , one to five cycles ) ; median number of days treated with sorafenib was 71 ( range , 4 to 620 days ) . The most common toxicities during cycle one were fatigue ( 94 % ) , anorexia ( 67 % ) , alterations in liver enzymes ( 64 % ) , and dermatologic adverse effects ( 48 % ) . Although most patients experienced at least one grade 3 to 4 toxicity , most toxicities were minor ( grade 1 to 2 , 83 % v grade 3 to 4 , 17 % ) . Toxicity during cycle two was decreased . Over the course of the study , there were 40 sorafenib dose interruptions and 25 sorafenib dose reductions . Sorafenib plus DEB-TACE was associated with a disease control rate of 95 % ( Response Evaluation Criteria in Solid Tumors Group)/100 % ( European Association for the Study of the Liver [ EASL ] ) , with an objective response of 58 % ( EASL ) . CONCLUSION The combination of sorafenib and DEB-TACE in patients with unresectable HCC is well tolerated and safe , with most toxicities related to sorafenib . Toxicity is manageable with dose adjustment of sorafenib . Preliminary efficacy data are promising PURPOSE This phase II study of sorafenib , an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases , assessed efficacy , toxicity , pharmacokinetics , and biomarkers in advanced hepatocellular carcinoma ( HCC ) patients . METHODS Patients with inoperable HCC , no prior systemic treatment , and Child-Pugh ( CP ) A or B , received continuous , oral sorafenib 400 mg bid in 4-week cycles . Tumor response was assessed every two cycles using modified WHO criteria . Sorafenib pharmacokinetics were measured in plasma sample s. Biomarker analysis included phosphorylated extracellular signal regulated kinase ( pERK ) in pretreatment biopsies ( immunohistochemistry ) and blood-cell RNA expression patterns in selected patients . RESULTS Of 137 patients treated ( male , 71 % ; median age , 69 years ) , 72 % had CP A , and 28 % had CP B. On the basis of independent assessment , three ( 2.2 % ) patients achieved a partial response , eight ( 5.8 % ) had a minor response , and 46 ( 33.6 % ) had stable disease for at least 16 weeks . Investigator-assessed median time to progression ( TTP ) was 4.2 months , and median overall survival was 9.2 months . Grade 3/4 drug-related toxicities included fatigue ( 9.5 % ) , diarrhea ( 8.0 % ) , and h and -foot skin reaction ( 5.1 % ) . There were no significant pharmacokinetic differences between CP A and B patients . Pretreatment tumor pERK levels correlated with TTP . A panel of 18 expressed genes was identified that distinguished " nonprogressors " from " progressors " with an estimated 100 % accuracy . CONCLUSION Although single-agent sorafenib has modest efficacy in HCC , the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents Until now , no effective systemic treatment options have been available for patients with unresectable advanced hepatocellular carcinoma ( HCC ) . In the Sorafenib Hepatocellular Carcinoma Assessment R and omized Protocol ( SHARP ) , patients with unresectable advanced HCC with Child – Pugh liver function class A and who had not received prior systemic therapy , received either oral sorafenib ( 400 mg twice daily ) or placebo until radiological and symptomatic progression . The two groups of patients were well balanced with respect to baseline characteristics . The study was stopped at the second planned interim analysis because of an advantage in the median overall survival ( 10.7 vs 7.9 months ; hazard ratio : 0.69 ; 95 % CI : 0.55–0.87 ; p < 0.001 ) and the median time to radiological progression ( 5.5 vs 2.8 months ; p < 0.001 ) in the sorafenib arm . However , sorafenib was not able to increase the time to symptomatic progression . In terms of toxicity , there were more cases of diarrhea , weight loss , h and –foot skin reaction and hypophosphatemia among the patients receiving sorafenib , the majority of which were of grade 1 or 2 severity . The SHARP trial has demonstrated that sorafenib is effective in prolonging median survival and time-to-progression in patients with advanced HCC and that it is generally well tolerated with a manageable adverse events profile BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies BACKGROUND In Japan and South Korea , transarterial chemoembolisation ( TACE ) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma ( HCC ) . Sorafenib , a multikinase inhibitor , has been shown effective and safe in patients with advanced HCC . This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE . METHODS Patients ( n=458 ) with unresectable HCC , Child-Pugh class A cirrhosis and ≥25 % tumour necrosis/shrinkage 1 - 3 months after 1 or 2 TACE sessions were r and omised 1:1 to sorafenib 400 mg bid or placebo and treated until progression/recurrence or unacceptable toxicity . Primary end-point was time to progression/recurrence ( TTP ) . Secondary end-point was overall survival ( OS ) . FINDINGS Baseline characteristics in the two groups were similar ; > 50 % of patients started sorafenib>9 weeks after TACE . Median TTP in the sorafenib and placebo groups was 5.4 and 3.7 months , respectively ( hazard ratio ( HR ) , 0.87 ; 95 % confidence interval ( CI ) , 0.70 - 1.09 ; P=0.252 ) . HR ( sorafenib/placebo ) for OS was 1.06 ( 95 % CI , 0.69 - 1.64 ; P=0.790 ) . Median daily dose of sorafenib was 386 mg , with 73 % of patients having dose reductions and 91 % having dose interruptions . Median administration of sorafenib and placebo was 17.1 and 20.1 weeks , respectively . No unexpected adverse events were observed . INTERPRETATION This trial , conducted prior to the reporting of registration al phase III trials , found that sorafenib did not significantly prolong TTP in patients who responded to TACE . This may have been due to delays in starting sorafenib after TACE and /or low daily sorafenib doses Background Disease progression of hepatocellular cancer ( HCC ) in patients eligible for liver transplantation ( LTx ) occurs in up to 50 % of patients , result ing in withdrawal from the LTx waiting list . Transarterial chemoembolization ( TACE ) is used as bridging therapy with highly variable response rates . The oral multikinase inhibitor sorafenib significantly increases overall survival and time-to-progression in patients with advanced hepatocellular cancer . Design The HeiLivCa study is a double-blinded , controlled , prospect i ve , r and omized multi-centre phase III trial . Patients in study arm A will be treated with transarterial chemoembolization plus sorafenib 400 mg bid . Patients in study arm B will be treated with transarterial chemoembolization plus placebo . A total of 208 patients with histologically confirmed hepatocellular carcinoma or HCC diagnosed according to EASL criteria will be enrolled . An interim patients ' analysis will be performed after 60 events . Evaluation of time-to-progression as primary endpoint ( TTP ) will be performed at 120 events . Secondary endpoints are number of patients reaching LTx , disease control rates , OS , progression free survival , quality of live , toxicity and safety . Discussion As TACE is the most widely used primary treatment of HCC before LTx and sorafenib is the only proven effective systemic treatment for advanced HCC there is a strong rational to combine both treatment modalities . This study is design ed to reveal potential superiority of the combined TACE plus sorafenib treatment over TACE alone and explore a new neo-adjuvant treatment concept in HCC before LTx LBA154^ Background : The global SPACE trial was conducted to evaluate the efficacy and safety of S in combination with TACE with DEBDOX in patients ( pts ) with intermediate-stage HCC ( BCLC B ) . METHODS Pts were eligible if they had asymptomatic , unresectable , multinodular tumors without vascular invasion ( VI ) or extrahepatic spread ( EHS ) ; Child-Pugh A liver functional status ; and ECOG PS 0 . Pts were r and omized to receive S 400 mg bid or matching P continuously ( 1 cycle = 4 wks ) until progression . All pts received TACE with DEBDOX ( 150 mg doxorubicin ; Biocompatibles UK Ltd ) 3 - 7d after first dose of study drug , and then on d1 ( ±4d ) of months 3 , 7 , and 13 , and q6 months thereafter . The primary endpoint was time to radiologic progression ( TTP ) by independent review ( predefined alpha = 0.15 ) . Secondary endpoints were overall survival ( OS ) , time to VI/EHS , time to untreatable progression ( TTUP ) , and safety . RESULTS Of 452 pts screened , 307 were r and omized to S ( n=154 ) or P ( n=153 ) . The HR for TTP was 0.797 ( 95 % CI , 0.588 , 1.080 ; p=0.072 ) . Median TTP ( 50th percentile ) was 169d/166d in the S and P groups , respectively ; TTP at the 25th and 75th percentiles ( preplanned ) was 112/88d and 285/224d in the S and P groups , respectively . There were no unexpected safety findings . Median treatment duration in the S and P groups was 4.8 and 6.3 months , respectively , and median daily dose of study drug was 566 mg and 791 mg , respectively . CONCLUSIONS The study met its primary endpoint of improving TTP when S was added to a regimen of TACE with DEBDOX , compared with TACE with DEBDOX alone . The combination was well tolerated ; no new safety findings that would preclude use of the combination were observed . The encouraging efficacy signal requires confirmation with data from ongoing phase III trials evaluating the combination of S plus TACE . [ Table : see text ] BACKGROUND No effective systemic therapy exists for patients with advanced hepatocellular carcinoma . A preliminary study suggested that sorafenib , an oral multikinase inhibitor of the vascular endothelial growth factor receptor , the platelet-derived growth factor receptor , and Raf may be effective in hepatocellular carcinoma . METHODS In this multicenter , phase 3 , double-blind , placebo-controlled trial , we r and omly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or placebo . Primary outcomes were overall survival and the time to symptomatic progression . Secondary outcomes included the time to radiologic progression and safety . RESULTS At the second planned interim analysis , 321 deaths had occurred , and the study was stopped . Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group ( hazard ratio in the sorafenib group , 0.69 ; 95 % confidence interval , 0.55 to 0.87 ; P<0.001 ) . There was no significant difference between the two groups in the median time to symptomatic progression ( 4.1 months vs. 4.9 months , respectively , P=0.77 ) . The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( P<0.001 ) . Seven patients in the sorafenib group ( 2 % ) and two patients in the placebo group ( 1 % ) had a partial response ; no patients had a complete response . Diarrhea , weight loss , h and -foot skin reaction , and hypophosphatemia were more frequent in the sorafenib group . CONCLUSIONS In patients with advanced hepatocellular carcinoma , median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo . ( Clinical Trials.gov number , NCT00105443 . Hepatocellular carcinoma ( HCC ) is a highly prevalent disease in many Asian countries , accounting for 80 % of victims worldwide . Screening programs improve the detection of early HCC and have a positive impact on survival , but the majority of HCC patients in Asia still present with advanced stage disease . The treatment outcomes of HCC are affected by multiple variables , including liver function , performance status of the patient , and tumor stage . Therefore , it is not easy to apply a multidisciplinary therapeutic approach for optimal management . At present , limited numbers of HCC patients are eligible for curative therapies such as surgery or ablation in Asia . Therefore , most patients are eligible for only palliative treatments . For optimal management , the treatment choice is guided by staging systems and treatment guidelines . Numerous staging systems have been proposed and treatment guidelines vary by region . According to the Barcelona Clinic Liver Cancer ( BCLC ) guideline based on evidence from r and omized clinical trials , only transarterial chemoembolization ( TACE ) is recommended for intermediate stage HCC and sorafenib for advanced stage HCC . However , treatment guidelines from Asian countries have adopted several other therapeutic modalities such as a surgical approach , hepatic arterial infusion chemotherapy , external radiation , and their combinations based on clinical experiences for intermediate and advanced stage HCC . Although TACE is the main therapeutic modality in the intermediate stage , overall therapeutic outcomes depend on the tumor size . In the advanced stage , the prognosis depends on the tumor status , e.g. major vessel invasion or extrahepatic spread . Thus , a new staging system representing prognoses suitable for Asian HCC patients and a corresponding optimal treatment algorithm should be further investigated using evidence -based data , which will finally bring about an Asian consensus for the management of intermediate and advanced stage HCC This paper is an overview of the new response evaluation criteria in solid tumours : revised RECIST guideline ( version 1 . 1 ) , with a focus on up date d contents BACKGROUND AND AIM It is unknown whether sorafenib can be combined with transarterial chemoembolization ( TACE ) in patients with hepatocellular carcinoma . This study assesses the safety and tolerability of a continuous regimen of sorafenib combined with TACE . METHODS This was an open-label phase I study testing a continuous administration of sorafenib ( dose escalation from 200 mg twice daily [ bid ] to 400 mg bid ) starting 7 days prior to TACE with doxorubicin ( 50 mg ) . RESULTS Twenty-one patients were screened and 14 received sorafenib combined with TACE . Because there were no dose-limiting toxicities in the first three patients who received sorafenib at a dose of 200 mg bid , subsequent patients received 400 mg bid . Twenty-seven procedures were performed ( median , two per patient ) and two local therapy-related severe adverse events occurred . The median duration of sorafenib therapy was 246 days ( range , 14 - 547 days ) . Sorafenib-related adverse events of grade ≥3 were h and -foot skin reaction ( n = 3 ) , weight loss ( n = 2 ) , diarrhea ( n = 1 ) , abdominal pain ( n = 1 ) , and thrombocytopenia ( n = 3 ) . After treatment with sorafenib and TACE , there was a significant decrease in the concentration of plasma vascular endothelial growth factor ( VEGF ) from 93 ng/l to 67 ng/l . CONCLUSIONS Continuous administration of sorafenib at a dose of 400 mg bid combined with TACE was tolerable . The adverse event profile of this regimen was comparable with that of sorafenib monotherapy with the exception of thrombocytopenia , which may be more frequent . There were no increases in the circulating VEGF levels after TACE with this combined regimen . ( Swiss Association for the Study of the Liver study number 25 ; Clinical Trials.gov trial identifier , NCT00478374 ) The role of bridging therapies for patients with hepatocellular carcinoma ( HCC ) on the waiting list for liver transplantation ( LT ) remains controversial . There is strong evidence to support the effectiveness of sorafenib in extending the time to progression of HCC . Using a Markov model , we compared two strategies : one using sorafenib as neoadjuvant therapy before LT ( Strategy A ) , and the other using no bridging therapy in the first 6 months ( Strategy B ) . Reference case : T2 HCC patient with compensated cirrhosis . The benefit of sorafenib in delaying time to HCC progression was expressed as the hazard ratio ( HR ) and taken from recently published r and omized trials . The endpoints considered were : survival benefit measured in quality ‐adjusted life days ( QALDs ) , transplant probability , costs ( C ) in € , willingness to pay ( WTP ) , and net health benefit ( NHB ) , where NHB = survival benefit − C/WTP . The calculated WTP of sorafenib in Italy was 346 € per QALD . Probabilistic sensitivity analysis showed a median survival benefit of 94 QALDs ( 10 % percentile = 38 , 90 % percentile = 210 ) . In the base‐case scenario ( HR = 0.47 , monthly dropout probability = 5 % , median time to LT = 3 months ) , the gain in LT probability due to sorafenib was 5 % and it increased proportionally with increasing median times to LT and decreasing HR . In the cost‐benefit analysis , the incremental NHB of Strategy A versus Strategy B was 37 QALDs ; it increased as sorafenib HR decreased and when median times to LT were shorter than 6 months , whereas for longer times it gradually dropped , particularly when Strategy B included effective locoregional treatments . Conclusion : Sorafenib neoadjuvant therapy is cost‐effective by comparison with no therapy for T2‐HCC patients waiting for LT , particularly for median times to LT under 6 months . ( HEPATOLOGY 2009 . BACKGROUND Recurrence of hepatocellular carcinoma ( HCC ) is a major problem after surgical or ablative treatments . The aim of this prospect i ve , single-center , placebo-controlled , r and omized , double-blind clinical study was to evaluate the effectiveness of transarterial chemoembolization ( TACE ) combined with sorafenib as a sequential treatment regimen in delaying time to progression ( TTP ) of intermediate-stage HCC in patients with chronic hepatitis C virus ( HCV ) infection . MATERIAL AND METHODS Between October , 2007 and January , 2011 , 80 HCV-infected patients with Barcelona Clinic Liver Cancer stage B HCC underwent the TACE procedure . All had Child-Pugh class A disease . They were r and omized 1:1 to receive sorafenib at a dose of 400 mg twice daily or placebo . Endpoints were the TTP and the rates of adverse events and toxicity . RESULTS Sixty-two of 80 patients ( 77 % ) , 31 in the sorafenib group and 31 in the control group , completed the study . The median TTP was 9.2 months in the sorafenib group and 4.9 months in the placebo group ( hazard ratio , 2.5 ; 95 % confidence interval , 1.66 - 7.56 ; p < .001 ) . Metachronous , multicentric HCC progression occurred less frequently in sorafenib-treated patients ( p < .05 ) . Adverse reactions to sorafenib caused withdrawal from the study of 9 ( 22 % ) patients . CONCLUSION A conventional TACE procedure followed by sorafenib treatment result ed in a significantly longer TTP in patients with intermediate-stage HCV-related HCC , with no unexpected side effects |
1,607 | 24,060,096 | Sensitivity analyses indicated that admission rate had the largest impact on results .
CONCLUSIONS Fetal fibronectin testing has moderate accuracy for predicting PTB .
The main potential role is likely to be reducing health-care re source usage by identifying women not requiring intervention .
Evidence from RCTs suggests that fFN does not increase adverse outcomes and may reduce re source use .
The base-case analysis showed a modest cost difference in favour of fFN testing , which is largely dependent on whether or not fFN testing reduces hospital admission . | BACKGROUND Premature birth is defined as birth of before 37 completed weeks ' gestation .
Not all pregnant women showing symptoms of preterm labour will go on to deliver before 37 weeks ' gestation .
Hence , addition of fetal fibronectin ( fFN ) testing to the diagnostic workup of women with suspected preterm labour may help to identify those women who do not require active management , and thus avoid unnecessary interventions , hospitalisations and associated costs .
OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of rapid fFN testing in predicting preterm birth ( PTB ) in symptomatic women . | OBJECTIVES To examine how the availability of fetal fibronectin testing affects the utilization of hospital re sources . METHODS A comparison of the rates , duration , and costs of hospitalization for a prospect i ve cohort of women who presented with preterm labour after fetal fibronectin ( Ffn ) testing became available , and a historical baseline cohort who presented with preterm labour before fetal fibronectin testing was available . The study included singleton pregnancies presenting between 24 and 34 weeks ' gestation with signs and symptoms of preterm labour . The women in each study cohort presented during a design ated 20-week period . RESULTS We examined the records of 116 subjects with comparable gestational age distributions in each 20-week period . During the study period when Ffn testing was available , 51 tests were performed . Four tests were invalid , and 12 subjects who were tested did not meeting the inclusion criteria . Admissions for preterm labour in the study period were significantly less than in the baseline cohort ( 12.1 % vs. 24.1 % , P = 0.03 ) , with no difference in preterm births ( 8.6 % vs. 7.8 % ) . The mean length of stay per patient with preterm labour declined from 5.2 days to 0.6 days ( P < 0.0001 ) , and the mean cost per patient with preterm labour declined from $ 3666 to $ 581 ( P < 0.0001 ) . In the 20-week study period , there was a reduction in total length of hospital stay from 145 to 28 days , with an overall reduction in total cost from $ 102 660 to $ 26 169 . CONCLUSION The availability of Ffn testing was associated with a reduction in hospital admissions , length of hospital stay , and overall hospital costs in the management of threatened preterm labour OBJECTIVE : To assess the impact of activity restriction ( AR ) on the incidence of preterm birth in women treated for preterm labor testing negative for fetal fibronectin ( fFN ) . STUDY DESIGN : Women who were diagnosed with preterm labor and tocolyzed with magnesium sulfate were concurrently screened with fFN for the purpose of subsequent management . Included were consenting patients with negative fFN , gestational age 23 0/7–33 6/7 weeks , cervical dilation ≤3 cm , and minimal vaginal bleeding . Patients were r and omized to AR or no AR . Primary study outcome was incidence of preterm delivery and interval from r and omization to delivery . RESULTS : A total of 73 women with negative fFN were r and omized ( 36 with AR , 37 without AR ) . The overall preterm birth rate was 40 % , with 44.4 % of patients with AR and 35.1 % of patients without AR delivering preterm , p=0.478 . CONCLUSION : Maternal AR did not impact pregnancy outcome . The incidence of preterm birth in symptomatic women testing fFN negative was higher than previously reported This week , a series of four articles considers the place of the r and omised controlled trial as we approach the second century of experience with the concept . Its basic principle is genuine uncertainty as to which treatment arm of the trial it would be in a patient 's best interests to enter . This is not necessarily an easy concept to transmit , OBJECTIVE We sought to investigate if determination of cervicovaginal interleukin-6 ( IL-6 ) levels would enhance the positive predictive value of fetal fibronectin ( fFN ) for preterm birth . METHODS A prospect i ve cohort study was undertaken of 135 women between 24 and 34 weeks gestation with symptoms of suspected preterm labor . Cervicovaginal secretions were collected for both IL-6 and fFN and measured by immunoassay and ELISA , respectively . Outcome variables included preterm delivery in less than 48 h , within 7 days , and prior to 37 weeks . Statistical analysis was performed with Fisher 's exact test , regression for logarithmic transform levels , and multivariate logistic regression . ROC curves were created for IL-6 levels . RESULTS IL-6 and fFN levels were both elevated in cervicovaginal secretions of women with symptoms of preterm labor . IL-6 values > 100 pg/ml result ed in a odds ratio for delivery at < 37 weeks of 1.57 ( 95%CI=0.89 - 2.75 , P=.11 ) , whereas fFN values > 50 ng/ml result ed in a preterm delivery risk of 4.58 ( 95%CI=1.54 - 13.35 , P=.003 ) . Combining IL-6 and fFN results did not improve upon the predictive value of fFN alone for preterm birth [ odds ratio 4.00 ( 95%CI=1.31 - 12.17 , P=.015 ) ] . CONCLUSION Cervicovaginal IL-6 levels did not provide any additional , independent effect on the prediction of preterm birth beyond that of fFN testing alone Aims The purpose of this pilot study was to determine the role of foetal fibronectin ( fFN ) testing in women presenting to hospital with symptoms of preterm labour in reducing the hospital admissions , without significantly increasing the risk of preterm birth and neonatal respiratory distress syndrome . Methods Women with symptoms of preterm labour were assigned r and omly to receive fFN ( n = 44 ) or to preterm labour management without fFN ( n = 44 ) . In the testing arm , the result of the test was revealed to the clinician . Clinical outcomes were compared in the two groups . The time period covered by the r and omised controlled trial ( RCT ) was from December 2007 to March 2009 . The RCT was conducted in two large maternity units in the west of Scotl and , one in Glasgow the other in Ayrshire . Results All the women with fibronectin positive got admitted while only 32.4 % of the fibronectin negatives were admitted ( P = 0.002 ) . There was a significant difference in the mean length of stay between the fibronectin positives which was 47.17 h , and the negatives which was 12.9 h ( P = 0.018 ) . Overall the control and testing arms did not differ in respect to admissions and length of stay . 5 out of 7 positives and 11 out of 37 negatives had corticosteroids ( P = 0.089 ) . 2 out of 7 positives and 1 out of 37 negatives had tocolytics ( P = 0.073 ) . Conclusions Those who had the fFN test done were less likely to be admitted in the hospital and had a shorter length of stay , without any increase in the adverse maternal or foetal effects , avoiding unnecessary admissions OBJECTIVE To assess the clinical value of cervicovaginal fetal fibronectin ( FFN ) in the prediction of preterm delivery ( PTD ) in women with signs and symptoms of preterm labor ( PTL ) . METHOD This investigation prospect ively studied a cohort of a women with symptoms of PTL , between 24 and 37 weeks ' gestation with < 3 cm of cervical dilatation and intact membranes . Cases were evaluated in terms of maternal demographic characteristics like age , body mass index , number of parities , previous PTL history , Bishop scores at admission , gestational age at delivery , mode of delivery , use of tocolytic or steroids , presence of histologic chorioamnionitis , neonatal outcomes and delivery before 34 weeks ' gestation as well as within seven days of admission . RESULTS A total number of 68 cases were included in the study . There were no statistically significant differences between positive and negative FFN groups in terms of maternal characteristics , mode of delivery and adverse neonatal outcomes . However , FFN + cases had higher Bishop scores on admission ( 3.4 + /- 1.2 vs 2.5 + /- 0.3 , p = 0.03 ) and lower gestational age at delivery ( 33.4 + /- 3.1 weeks vs 36.8 + /- 2.1 weeks , p = 0.002 ) . Likelihood ratio ( LR ) for positive results was 1.83 ( 95 % CI : 1.61 - 2.26 ) for predicting birth before 34 weeks ' gestation , with a corresponding negative LR of 0.62 ( 95 % CI : 0.3 - 1.2 ) . LR for positive results was 4.34 ( 95 % CI : 3.65 - 5.12 ) for predicting birth within seven days of testing , with a corresponding negative LR of 0.3 ( 95 % CI : 0.2 - 0.5 ) . CONCLUSION Based on the results of cervicovaginal FFN , positive tests represent an increased likelihood of PTD among women with symptoms of threatened preterm labor OBJECTIVE The purpose of this study was to codify the relationship between bacterial vaginosis/fetal fibronectin and preterm labor/birth . STUDY DESIGN In this prospect i ve study , 185 women who were symptomatic for preterm labor were assessed for bacterial vaginosis and fetal fibronectin . RESULTS These women comprised 4 groups : group A ( n=23 women ; + bacterial vaginosis/+fetal fibronectin ) ; group B ( n=31 women ; -bacterial vaginosis/+fetal fibronectin ) ; group C ( n=47 women ; + bacterial vaginosis/-fetal fibronectin ) ; and group D ( n=84 women ; -bacterial vaginosis/-fetal fibronectin ) . The time interval from gestational age at testing until delivery was significantly shorter for groups A and B versus groups C and D ( P < or = .05 and P < .001 , respectively ) . Similarly , delivery at < 32 weeks of gestation was increased in group B ( 26 % ) compared with groups A ( 9 % ) , C ( 2 % ) , and D ( 5 % ; P < .009 ; odds ratio , 165.90 ; 95 % CI , 30.02 , 916.08 ) . CONCLUSION Women who are symptomatic for preterm labor should be considered for fetal fibronectin and bacterial vaginosis testing OBJECTIVE Our purpose was to determine whether tumor necrosis factor-alpha , interleukin-6 , and fetal fibronectin could be identified in the lower genital tract during pregnancy and whether their occurrence was associated with preterm delivery . STUDY DESIGN A prospect i ve cohort study was undertaken of 111 pregnant women in which cervicovaginal swabs were obtained at < 37 weeks ' gestation . Seventy-three specimens were obtained from women during routine prenatal examination , whereas 38 specimens were obtained from women undergoing evaluation of preterm labor . Interleukin-6 and fetal fibronectin levels were determined by enzyme-linked immunosorbent assays , whereas tumor necrosis factor-alpha determinations were by bioassay . Urinary tract and lower genital tract sample s were cultured for evidence of infection . The rates of maternal and neonatal complications were assessed . RESULTS In patients undergoing evaluation for preterm labor the presence of tumor necrosis factor-alpha or fetal fibronectin was associated with an increased prevalence of preterm delivery . Women with tumor necrosis factor-alpha had a 6.19 greater risk ( p < 0.005 ) , whereas the presence of fetal fibronectin was associated with a 4.81 greater risk ( p < 0.05 ) , of preterm birth . This association was not evident in women who were sample d during routine prenatal examinations . In all women the presence of cytokines in the lower genital tract correlated with detection of fetal fibronectin . CONCLUSION Localized inflammatory responses may lead to microscopic disruption in the amniotic membranes , leading to leakage of fibronectin . In patients being evaluated for preterm labor , the presence of tumor necrosis factor-alpha or fetal fibronectin in the lower genital tract is predictive of subsequent preterm delivery Objective To assess the accuracy of vaginal fetal fibronectin ( FFN ) as a screening test for preterm delivery in a community hospital . Study design A prospect i ve cohort of patients at high risk for preterm delivery at a community hospital underwent testing with FFN over a 15 month-period ( March 2004–May 2005 ) . Indications for testing were preterm labor , multiple pregnancies , cervical shortening , and cerclage . Pregnancy characteristics were retrieved on all women with positive FFN results and controls in a 1:2 ratio . Outcome variables included interval to delivery ; length of hospital stay ; and rates of preterm delivery < 37 weeks . In the presence of serial FFN testing , only the initial result was used for calculation of diagnostic indices . Statistical analysis utilized t-test , Fisher ’s exact test and logistic regression analyis to control for gestational age at testing , with P < 0.05 or odds ratio ( OR ) with 95 % confidence interval ( CI ) not inclusive of the unity considered significant . Results Two hundred and fifty seven FFN tests were performed in 230 women , of which 33 ( 14.3 % ) had positive FFN results . Duration of hospital stay was significantly shorter for patients with negative than positive results ( 8 h vs. 2.1 days , P = 0.011 ) . Women with positive FFN were more likely to deliver within 14 days ( OR = 6.5 , 95 % CI 1.4 ; 30.7 ) , within 21 days ( OR = 4.8 ; 95 % CI 1.4 ; 16.6 ) , before 34 weeks ( OR = 5.0 , 95 % CI 1.7 ; 14.8 ) and before 37 weeks ( OR = 3.1 ; 95 % CI 1.3 ; 7.1 ) than women with negative results . Conclusion A negative FFN result provides enough reassurance to allow shorter hospital stay . In a real-world setting ( a community hospital with a population heterogenous for risk factors for preterm delivery , and in a non- protocol setting ) the performance of FFN testing closely mirrors that obtained in academic institutions , where the test was studied in more uniform population s under strict protocol s. Summary The performance of vaginal fibronectin in patients with heterogeneous risk factors for preterm delivery closely mirrors that obtained in studies conducted in population s with homogeneous risk factors OBJECTIVE The objective of the study was to determine the relationship between fetal fibronectin ( fFN ) testing prior to ultrasound-indicated cerclage and obstetric outcome . STUDY DESIGN Singleton pregnancies between 18 and 24 weeks ' gestation with an ultrasound-diagnosed short cervix ( < 25 mm ) and funneling ( > 25 % ) of the chorioamniotic membranes into the endocervical canal were analyzed . The fFN testing was performed and patients were r and omized to cerclage or no-cerclage . Groups were stratified by fFN result . Cerclage patients were compared with no-cerclage patients . The primary outcome was delivery prior to 35 weeks ' gestation . RESULTS Spontaneous preterm birth prior to 35 weeks ' gestation occurred in 15 ( 44.1 % ) fFN-positive-cerclage patients and 16 ( 55.2 % ) fFN-positive no-cerclage patients ( P = .45 ) . Similarly , it occurred in 16 ( 17.8 % ) fFN-negative cerclage patients and 11 ( 17 % ) fFN-no-cerclage patients ( P = .99 ) . CONCLUSION fFN did not identify optimal c and i date s for cerclage . However , fFN testing before an ultrasound-indicated cerclage aids in counseling patients , anticipating the outcome of pregnancies complicated by cervical shortening OBJECTIVE To determine the prognostic value of foetal fibronectin and cervical length for predicting imminent preterm labour among Dutch women , who in the Netherl and s normally undergo a digital examination of the cervix prior to referral to a hospital or university medical centre . DESIGN Prospect i ve observational cohort study . METHODS Pregnant women with symptoms of preterm labour and a gestational age between 24 and 34 weeks were included . A fibronectin smear was taken from them and the cervical length was measured . Primary outcome was delivery within 7 days after inclusion . Sensitivity , specificity and a receiver-operating characteristics ( ROC ) curve were calculated . RESULTS 13 ( 12 % ) of the 108 included patients delivered spontaneously within 7 days after inclusion . The fibronectin test had a sensitivity of 92 % and specificity of 60 % . The positive and negative predictive values were 27 % and 98 % respectively . For women who had undergone a digital examination prior to testing , the predictive value was slightly less but the difference was not significant . Although measurement of the cervical length scarcely had a predictive value , none of the patients with a cervical length above 35 mm delivered within 7 days . CONCLUSION In women with an imminent preterm labour , a negative fibronectin test virtually ruled out delivery within 7 days . The fibronectin test can therefore also be used in the Dutch situation . In women with a cervix length greater than 35 mm , the chance of a preterm labour within 7 days is very small and a fibronectin test does not need to be performed in their case OBJECTIVE Fetal fibronectin bedside testing has been proposed as a diagnostic tool for the accurate diagnosis of preterm labor . The study objective was to determine whether the introduction of routine fetal fibronectin bedside testing affected costs and transfer rates from referral district hospitals to a tertiary obstetric hospital , as well as direct admissions to a tertiary referral hospital . STUDY DESIGN We performed an 18-month prospect i ve audit of fetal fibronectin use in 9 referral hospitals and one university maternal-fetal medicine unit . Data collected were delivery details and cervical dilatation at admission . Cost savings in terms of transport costs for patients with a negative fetal fibronectin result who were not transferred or admitted to the tertiary center were calculated for interhospital transfer ( road ambulance or fixed-wing retrieval ) . RESULTS One hundred fifty-one patients had a presumptive diagnosis of threatened preterm labor . Forty-five patients had a positive fetal fibronectin result and 106 had a negative fetal fibronectin result ( 3 with cervical dilatation > /=3 cm ) . Eleven ( 24 % ) patients with a positive fetal fibronectin result were delivered within 7 days , and 5 ( 5 % ) with a negative fetal fibronectin result were delivered within 7 days . One patient was delivered at 34 weeks , and the remaining patients were delivered at or after 36 weeks ' gestation . All 3 patients with negative fetal fibronectin results with cervical dilatation of > /=3 cm were delivered within 5 days , leaving 2 ( 1.9 % ) patients ( with closed cervices and negative fetal fibronectin results ) being delivered 5 days after the fetal fibronectin testing . Ninety percent of the patients admitted to a referral hospital with threatened preterm labor who had a negative fetal fibronectin result were not transferred ; thus an unnecessary transfer was avoided , with cost savings ranging from $ 30,297 for road and fixed-wing transport . CONCLUSION A negative fetal fibronectin result is not helpful if cervical dilatation is present , and these patients should be treated as having a high risk of preterm delivery . The use of a fetal fibronectin test was associated with a 90 % reduction in maternal transfer and can substantially reduce the costs and inconvenience associated with unnecessary transfer OBJECTIVE To estimate the performance of the foetal fibronectin test as a predictor of preterm delivery . PATIENTS AND METHODS This prospect i ve study concern 61 patients who had a singleton pregnancy between 24 and 36 weeks of gestation and were hospitalized because of a threatened preterm labor without premature rupture of the membranes . For each patient the presence of foetal fibronectin in cervicovaginal secretions was determined with a rapid swab-test . RESULTS Prematurity rate was 38 % ( 23 patients ) . In case of positive result , delivery became before 37 weeks in 75 % ( 12/16 ) against 24 % in case of negative result ( 11/45 ) . The prolongation of pregnancy after the test was on average 21 days in the positive group and 44 days in the negative group . About the prediction of preterm delivery , the results showed a sensibility of 52 % , a specificity of 89 % , a positive predictive value of 75 % , a negative predictive value of 76 % . To predict a delivery within the two weeks after the test , the sensibility was 88 % , the specificity 83 % , and the negative predictive value 98 % . CONCLUSION The presence of foetal fibronectin in cervicovaginal secretions represent an increased risk of preterm delivery , whereas its excellent negative predictive value allow to be reassuring , especially within a period of 15 days OBJECTIVE The purpose of this study was to determine whether knowledge of the results of a rapid fetal fibronectin test affects treatment decisions during the evaluation and treatment of possible preterm labor . Previous observational studies have suggested that a negative test might help to avoid unnecessary intervention . STUDY DESIGN This was a r and omized study of women who were between 24 weeks and 34 weeks 6 days of gestation with symptoms of preterm labor and who were seen in three community hospitals . A rapid fetal fibronectin test was performed on all subjects . Patients were assigned r and omly to a group whose results were known to physician or to a group whose results were not known . Treatment decisions were at the discretion of the physician . RESULTS One hundred eight sample s were collected between September 2000 and December 2001 . There were 10 positive fetal fibronectin tests . The overall prevalence of delivery within 2 weeks for the study population was 2.8 % . For women who had negative fetal fibronectin test results , the hospital stay was not significantly shorter when the result was known ( 6.8 hours ) than when it was not known ( 8.1 hours , P = .35 ) . However , when the physician knew the fetal fibronectin status of women with a negative test result who were observed for > 6 hours , the hospital stay was shortened 40 % , to 22.7 hours from 37.8 hours ( P = .04 ) . CONCLUSION Fetal fibronectin testing may be able to supplement clinical judgment in the evaluation of the condition of patients with symptoms of preterm labor . The greatest benefit of fetal fibronectin testing might be for the patient whom the physician judges to be at high risk for imminent delivery . In such patients , the knowledge of a negative fetal fibronectin may shorten the hospital stay OBJECTIVE To evaluate the association between cervical oncofoetal fibronectin and prematurity as well as the interval between sampling and delivery in symptomatic women . METHODS Cervical fibronectin was measured with an immunoassay in a cohort of 64 women at the University Hospital of Geneva . Subjects with positive and negative fibronectin were then compared using the relative risk and the incidence rate ratio of premature delivery as well as the survival tables . Performance of the test to predict premature delivery or delivery within one week of the test were expressed in terms of sensitivity , specificity , predictive values and likelihood ratios with their 95 % confidence intervals . RESULTS Thirty-four percent of women delivered prematurely . The presence of fibronectin was significantly associated with premature delivery and with a shorter interval to delivery . The likelihood ratio for a positive test was 2.6(95 % CI : 1.45 - 4.66 ) . A negative test had a 100 % predictive value to exclude delivery within one week of the test . CONCLUSION Oncofoetal fibronectin appears to be the best marker currently available to predict premature delivery . A r and omized trial is needed to confirm its clinical usefulness OBJECTIVE Our aim was to determine whether the presence of fetal fibronectin in vaginal secretions of patients with symptoms suggestive of preterm labor predicts preterm delivery . STUDY DESIGN Patients who were examined at the hospital between 24 weeks ' and 34 weeks 6 days ' gestation with intact membranes , no prior tocolysis , symptoms suggestive of preterm labor , and cervical dilation < 3 cm were recruited at 10 sites . Swabs of the posterior fornix were assayed for the presence of fetal fibronectin by monoclonal antibody assay , with a positive result defined as > or = 50 ng/ml . Results were not available to the managing physicians . Tocolysis was used when clinical ly indicated after specimen collection . RESULTS A total of 763 patients had fetal fibronectin results and pregnancy outcome data available for analysis . Fetal fibronectin was detected in specimens from 150 ( 20 % ) patients . Compared with patients who had negative results , patients who had positive results for fetal fibronectin were more likely to be delivered within 7 days ( relative risk 25.9 [ 95 % confidence interval 7.8 to 86 ] ) , within 14 days ( relative risk 20.4 [ 95 % confidence interval 8.0 to 53 ] ) , and before 37 completed weeks ( relative risk 2.9 [ 95 % confidence interval 2.2 to 3.7 ] ) . The negative predictive values for delivery within 7 days , within 14 days , and at < 37 weeks were 99.5 % , 99.2 % , and 84.5 % , respectively . When we used multiple logistic regression analysis to control for potential confounding variables among singleton pregnancies , only the presence of fetal fibronectin ( odds ratio 48.8 , 95 % confidence interval 7.4 to 320 ) , prior preterm birth ( odds ratio 8.3 , 95 % confidence interval 1.5 to 46.6 ) , and tocolysis ( odds ratio 4.1 , 95 % confidence interval 1.0 to 16.0 ) were associated with birth within 7 days ; fetal fibronectin ( odds ratio 3.6 , 95 % confidence interval 2.2 to 5.9 ) , prior preterm birth ( odds ratio 2.5 , 95 % confidence interval 1.4 to 4.4 ) , cervical dilatation > 1 cm ( odds ratio 2.9 , 95 % confidence interval 1.6 to 5.2 ) , and tocolysis ( odds ratio 4.5 , 95 % confidence interval 2.8 to 7.2 ) were all independently associated with delivery before 37 weeks . CONCLUSION In a population of patients with symptoms , the presence of fetal fibronectin in vaginal secretions best defines a subgroup at increased risk for delivery within 7 days ; the high negative predictive value of fetal fibronectin sampling supports less intervention for patients with this result OBJECTIVES To determine prospect ively if dynamic cervical change ( spontaneous real-time cervical shortening ) is predictive of preterm delivery at < 37 weeks ' gestation in patients with symptoms of preterm labor . METHODS This was a prospect i ve study of patients at 23 - 34 weeks ' gestation who were symptomatic for preterm labor . Patients underwent a 10-min real-time sonographic cervical length assessment with measurements taken at 1-min intervals . The presence or absence of dynamic cervical change , defined as real-time changes in cervical length observable to the naked eye of the sonologist during the examination , was recorded . Gestational age at delivery was obtained from medical records . Preterm delivery was defined as delivery at < 37 weeks ' gestation . Dynamic cervical change and initial and minimum cervical lengths were assessed for prediction of preterm delivery . RESULTS Seventy-six patients were enrolled , and 66 were available for outcome analysis . Thirty-one patients ( 47 % ) exhibited dynamic cervical change . Patients with dynamic change had shorter initial cervical lengths ( 27 mm vs. 36 mm , P = 0.001 ) , shorter minimum cervical lengths ( 20 vs. 33 mm , P < 0.001 ) and larger changes in cervical length during the examination period ( 10 vs. 4 mm , P < 0.001 ) . In the subgroup of patients with an initial cervical length > 30 mm , those with dynamic change delivered earlier than did those without dynamic change ( 36.8 vs. 38.6 weeks , P = 0.02 ) , and a higher percentage delivered preterm ( 27 % vs. 11 % , odds ratio ( OR ) , 3.0 ( 0.5 - 17.0 ) ) . Multivariate analysis showed that minimum cervical length was a better predictor of preterm delivery than was initial cervical length . CONCLUSIONS Dynamic cervical change occurs frequently in association with shortened cervical length . In patients with longer initial cervical lengths , dynamic change may increase the risk for preterm delivery . When dynamic change is noted in a patient with preterm labor symptoms , use of the minimum cervical length observed may be better compared with initial cervical length for determining preterm delivery risk OBJECTIVE The purpose of this study was to investigate the effect of the rapid fetal fibronectin on the length of hospital stay and the use of preterm labor interventions in a tertiary care center . STUDY DESIGN Women who were seen in the Labor and Delivery Unit with symptoms of preterm labor were assigned r and omly to receive fetal fibronectin ( n=46 women ) or to preterm labor management without fetal fibronectin ( n=51 women ) . Physicians were not blinded to the result ; groups were compared . RESULTS There was no difference between groups in demographic or obstetric characteristics , the hours spent in labor and delivery , the number of women who were admitted to the antepartum service , the length of stay , or medical interventions . When the results for women with a negative fetal fibronectin test were compared to women with a positive fetal fibronectin test , a significant difference was found in admissions to the antepartum service ( P=.032 ) and the length of stay ( P=.008 ) . CONCLUSIONS A negative fetal fibronectin test was associated with fewer admissions to the antepartum ward and a shorter length of stay OBJECTIVE The purpose was to determine to what extent fetal fibronectin was a discriminative test of preterm delivery in patients hospitalized for uterine contractions without modification of the cervix . STUDY DESIGN The prospect i ve double-blind study included patients hospitalized between 24 and 34 week for false labor . Cervicovaginal swabs were obtained and assayed for the presence of fetal fibronectin by means of a monoclonal antibody assay . RESULTS Out of the 61 patients included , 18 showed a positive swab . The correlation of a positive result with preterm delivery revealed a sensitivity of 56 % , a specificity of 81 % , and positive and negative predictive values of 56 % and 81 % respectively . Meta- analysis of studies published shows that the presence of fibronectin represents a significant relative risk of 3.3 ( IC : 2.5 - 42 ) of preterm delivery . CONCLUSION The presence of fetal fibronectin in cervicovaginal secretions of patients presenting with false labor indicates a major risk of preterm delivery Objective . To determine whether cervical length ( CL ) measured by the Cervilenz ™ measuring device is an effective screening tool for the prediction of preterm delivery ( PTD ) compared to fetal fibronectin ( fFN ) . Methods . We evaluated fFN and CL among women who enrolled into a r and omized control trial ( RCT ) comparing management algorithms for threatened preterm labor between 24 and 34 weeks ' gestation . In all subjects , fFN was collected , with CL determined in blinded fashion . The sensitivity , specificity , and positive and negative predictive values ( NPV ) for fFN or Cervilenz in prediction of PTD within 7 days or prior to 37 weeks were determined . Results . Fifty-two subjects were evaluated . CL < 30 mm correlated with PTD < 7 days ( r = 0.31 , p = 0.04 ) and fFN positivity ( r = 0.43 , p = 0.006 ) . CL < 30 mm and fFN had excellent NPV for PTD < 7 days ( 97.1 vs. 97.3 % ) , and the area under the receiver operator characteristic curves were similar for prediction of PTD < 7 days ( 76.6 vs. 75.2 % , p = 0.71 ) or < 37 weeks ( 56.7 vs. 55.2 % , p = 0.71 ) . Conclusions . Measurement of CL with Cervilenz appears to be equivalent to fFN in screening symptomatic women for PTD within 7 days or prior to 37 weeks . Given cost and turnaround time with fFN testing , Cervilenz represents a promising new tool for real time , clinical ly useful results in the management of women with threatened preterm labor UNLABELLED BACGROUND : preterm birth is a major obstetric problem that contributes to 70 % of perinatal mortality . OBJECTIVE to determine the sensitivity , specificity and predictive values of fetal fibronectin and cervical length as predictors of preterm birth in the HGR No. 36 , Puebla . MATERIAL AND METHODS observational , prospect i ve . comparative study . Pregnant women were included between 24 and 33 weeks amenorrhea and diagnosis of preterm labor . Quik Chek Kit was used to detect fibronectin using qualitative methods , and then subjected to measurement of cervical length with endovaginal ultrasound . Patients with a positive result or both proceeded to start treatment . To calculate sensitivity , specificity and predictive values were used odds ratios and Fisher exact test for statistical analysis . RESULTS of 66 patients 34 % reported positive fibronectin with a sensitivity and PPV of 92 % and 77 % compared with the assessment of 27 % of patients with short cervical length at 55 % and 88 % respectively . 28 % had two positive marker ( fibronectin/cervical length ) , the sensitivity , specificity and positive and negative predictive values increased significantly ( 86 % , 100 % , 93 % , 100 % ) . The average time between birth positive test was observed at 21 days . Risk factors for preterm delivery were found : patients under 25 years ( P:0.0009 ) , primigravida ( P:0.0057 ) , genitourinary infection ( P:0.0001 ) . CONCLUSION the double marker fibronectin / cervical length is useful for determining patients at risk of preterm delivery because of its high specificity and NPV , ideal for easy h and ling and low cost OBJECTIVE The purpose of this study was to determine whether selective use of fetal fibronectin detection after ultrasound measurement of cervical length predicts preterm delivery in symptomatic patients better than either indicator alone . STUDY DESIGN This prospect i ve blinded study performed both tests on 359 women hospitalized for preterm labor between 18 and 34 completed weeks ' gestation . The primary outcome was preterm delivery before 35 weeks'gestation . RESULTS Among the 359 women included , 48 ( 13.4 % ) delivered before 35 weeks ' gestation . The sensitivity , specificity , and positive and negative predictive values of cervical length < or = 25 mm were 75 % , 63 % , 24 % , and 94 % , respectively , and of fetal fibronectin > or = 50 ng/mL , 63 % , 81 % , 33 % , and 93 % . Fetal fibronectin detection was significantly ( P < .001 ) more specific than cervical length measurement . For selective use of fetal fibronectin detection after cervical length measurement , the test was considered positive if cervical length was < or = 15 mm or if cervical length was between 16 and 30 mm with fetal fibronectin > or = 50 ng/mL. The predictive values of this test were not significantly different from those of fetal fibronectin detection ( 67 % , 81 % , 36 % , and 94 % ) . This strategy could have avoided 200 fibronectin tests . CONCLUSION Selective use of fetal fibronectin detection after cervical length measurement is more specific than cervical length and as effective as fetal fibronectin assays in the entire population of women in preterm labor for predicting preterm birth OBJECTIVE We sought to determine whether a single quantitative vaginal fetal fibronectin ( fFN ) test at 24 weeks ' gestational age ( GA ) can delineate the spectrum of risk of spontaneous preterm delivery ( sPTD ) in an asymptomatic high-risk population comprised of patients with a prior preterm birth . STUDY DESIGN We performed a secondary analysis of a prospect ively collected data set in asymptomatic patients at high risk with singleton gestations who underwent quantitative fFN screening at 24 weeks . Data from 563 women with a history of preterm delivery ( PTD ) were available . The association between quantitative fFN concentrations collected at 24 weeks and subsequent GA at delivery was analyzed . RESULTS The overall PTD rate < 34 weeks and < 37 weeks was 6.7 % and 19.7 % , respectively . In all , 497 of 563 patients ( 88 % ) at 24 weeks had an fFN level of 0 ng/mL. As the fFN concentrations increased , sPTD rates progressively increased . Compared with the fFN 0 ng/mL group , the relative risk for sPTD < 34 weeks was sequentially increased in each group , respectively : 2.42 ( fFN 1 - 49 ng/mL ; 95 % confidence interval [ CI ] , 0.76 - 5.66 ) , 4.68 ( fFN 50 - 199 ng/mL ; 95 % CI , 1.28 - 10.95 ) , and 9.94 ( fFN > 200 ng/mL ; 95 % CI , 2.90 - 19.67 ) . Similar trends were seen between groups at different GAs from 32 - 37 weeks . CONCLUSION In asymptomatic women with a prior PTD , quantitative fFN assessment at 24 weeks effectively delineates the risk of recurrent sPTD . Quantification of fFN may provide additional information regarding the spectrum of risk of subsequent sPTD than would be derived from the st and ard qualitative screen currently used OBJECTIVE This study was undertaken to determine whether fetal fibronectin determination is more useful for predicting preterm delivery in clinical practice than it has appeared to be in prospect i ve blinded studies . STUDY DESIGN Charts of 151 patients with fetal fibronectin tests performed during 2 years were review ed . Patients were included if they had symptoms of preterm labor , a singleton pregnancy at 24 to 35 weeks ' gestation , intact membranes , and cervical dilatation < or =3 cm . RESULTS Complete data were available for 85 tests . For delivery within 7 days after specimen collection the sensitivity , specificity , positive predictive value , and negative predictive value were 89 % , 84 % , 40 % , and 98 % , respectively . The positive predictive value was greater ( P < .002 ) than those reported in three prospect i ve studies evaluating delivery within 7 days in patients with symptoms . Gestational age at delivery and birth weight were lower for patients with positive results ( P < . 0001 and P < .006 , respectively ) . Patients with positive results were also treated more with tocolysis , corticosteroid use , and hospitalization than were patients with negative results . For direct comparison with studies of patients with cervical dilatation <3 cm , only 4 patients with cervical dilatation of 3 cm were enrolled . All 4 had negative results of fetal fibronectin testing , and their outcomes therefore did not affect the positive predictive value . CONCLUSION The positive predictive value of fetal fibronectin measured in actual clinical practice was significantly greater for delivery within 7 days than has been reported in blinded prospect i ve studies OBJECTIVE The purpose of this study was to determine whether a knowledge of fetal fibronectin results affects patient treatment and health care costs . STUDY DESIGN Women between 24 and 34 weeks of gestation with a singleton pregnancy and preterm uterine contractions were eligible for enrollment . Once informed consent was given , a fetal fibronectin specimen was obtained , and women were assigned r and omly into 2 groups . In 1 group , results of the fetal fibronectin test were available ; in the other group , results were not available . The use of inpatient and outpatient health care re sources subsequent to enrollment was ascertained through the use of medical records , hospital billing data , and patient interviews . This study was powered to allow the detection in the fetal fibronectin group of a 20 % reduction in total health care-related costs . RESULTS The 2 groups were similar with respect to maternal age , parity , race , cervical examination at admission , and estimated gestational age at enrollment and at delivery . Women who did not have fetal fibronectin results available were no different than those women who did with respect to initial length of labor and delivery observation ( median , 4 hours vs 3 hours ) , hospital admission ( 28 % vs 26 % ) , tocolysis ( 18 % vs 16 % ) , cessation of work ( 27 % vs 26 % ) , or total health care-related costs ( log mean + /- SD , 7.6 + /- 1.2 vs 7.5 + /- 1.1 ) . CONCLUSION In this study population , the use of fetal fibronectin did not affect physician behavior or health care costs related to preterm contractions CONTEXT Not all pregnant women with an " unripe " cervix can be successfully ripened by the cervical ripening agents ; therefore tests with predictive information are justified . OBJECTIVES To examine the effect of the presence of foetal fibronectin ( FFN ) in the cervico-vaginal secretions on pre-induction cervical ripening with either intravaginal Misoprostol or transcervical Foley catheter . METHODOLOGY Twenty ( 20 ) patients managed at a tertiary health institution in South-western Nigeria between March and May 2003 were r and omised for cervical ripening by either intravaginal Misoprostol or Transcervical Foley catheters . Cervico-vaginal secretions were assessed for presence of FFN with Foetal Fibronectin Enzyme Immunoassay Kit ( Adeza Corp. ) prior to commencement of cervical ripening . MAIN OUTCOME MEASURES FFN status , Pre-ripening and Pre-induction modified Bishop scores and duration of cervical ripening . RESULTS Ten of the fifteen patients with positive membrane immunoassay for FFN achieved ripened cervix ( modified Bishop score > or = 6 ) within 6 - 12 hours of exposure to the agents of cervical ripening . In the FFN negative group , only 2 of the five patients achieved ripe cervix within the > 12 - 18 hours period , the rest being in the > 18 - 24 hours period . CONCLUSION Foetal fibronectin test may offer useful predictive information prior to institution of processes of cervical ripening in patients with unfavourable cervices BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects OBJECTIVE The ability to accurately identify articles about therapy in large bibliographic data bases such as EMBASE is important for research ers and clinicians . Our study aim ed to develop optimal search strategies for detecting sound treatment studies in EMBASE in the year 2000 . METHODS H and search es of journals were compared with retrievals from EMBASE for c and i date search strategies . Six trained research assistants review ed fifty-five journals indexed in EMBASE and rated articles using purpose and quality indicators . C and i date search strategies were developed for identifying treatment articles and then tested , and the retrievals were compared with the h and - search data . The operating characteristics of the strategies were calculated . RESULTS Three thous and eight hundred fifty articles were original studies on treatment , of which 1,256 ( 32.6 % ) were method ologically sound . Combining search terms revealed a top performing strategy ( r and om:.tw . OR clinical trial:.mp . OR exp health care quality ) with sensitivity of 98.9 % and specificity of 72.0 % . Maximizing specificity , a top performing strategy ( double-blind:.mp . OR placebo:.tw . OR blind : .tw . ) achieved a value over 96.0 % , but with compromised sensitivity at 51.7 % . A 3-term strategy achieved the best optimization of sensitivity and specificity ( r and om:.tw . OR placebo:.mp . OR double-blind:.tw . ) , with both these values over 92.0 % . CONCLUSION Search strategies can achieve high performance for retrieving sound treatment studies in EMBASE & NA ; Elevated levels of fetal fibronectin ( fFN ) in cervicovaginal secretions beyond 20–22 weeks of gestation are used as a predictor of preterm birth in patients with corroborative symptoms and signs . Aim : To assess the impact of introducing the fFN assay on the diagnosis , length of hospital stay and cost of managing patients presenting with symptoms of premature labour in our hospital . Methods : The first 30 fFN‐tested patients ( fFN group ) were prospect ively recruited and followed up until delivery . Hospital stay and management costs ( costs of individual tests and treatment administered ) and neonatal outcomes were compared with 30 matching historical controls . Results : Overall management costs of the fFN‐group were comparable with controls ( NZ$918 versus NZ$943 per patient , p=0.44 ) . The fFN‐group had a trend towards reduced length of hospital stay ( p=0.082 ) , less tocolysis ( p=0.002 ) and use of steroids ( p<0.001 ) . The cost of managing an fFN‐positive patient was more than an fFN‐lnegative patient , but not statistically significant ( NZ$1117 versus NZ$846 , respectively , p=0.11 ) . Conclusion : Despite a trend towards reduced hospital stay and less use of obstetric intervention , total expenditure in patient management has not reduced with the availability of the fFN assay in our hospital . This may only reflect the slow introduction of a new policy that with time may be implemented to full effect OBJECTIVE Our objective was to determine whether fetal fibronectin is a discriminator for preterm labor and early delivery in women who have intact membranes and uterine activity . STUDY DESIGN In our prospect i ve study 28 women between 24 and 34 weeks ' gestation with regular , persistent uterine contractions ( > 10/hr ) and intact membranes were assessed for presence of fetal fibronectin . A Dacron swab was applied to the external os for 10 seconds . The cervix was < or = 1 cm , and all patients were diagnosed as having false labor . The assay was performed by using monoclonal antibody FDC-6 to bind fetal fibronectin . RESULTS Of the 28 patients with false labor , 14 had a positive fetal fibronectin , and all had preterm labor ( specificity and positive predictive value 100 % ) . Of these , nine delivered preterm , yielding a specificity and positive predictive value of 72 % and 64 % , respectively . Among the 14 women with a negative fetal fibronectin , only four developed preterm labor ( sensitivity 78 % , negative predictive value 71 % ) . One patient delivered preterm at 34 weeks ( sensitivity 90 % and negative predictive value 93 % ) . CONCLUSIONS A positive fetal fibronectin in women who have false labor indicates a significant risk for preterm labor and early delivery . A negative fetal fibronectin is a reassuring sign OBJECTIVE : To evaluate the relationship between fetal fibronectin and preterm birth and maternal-to-child transmission of human immunodeficiency virus ( HIV ) in an African population of predominantly HIV-infected women . METHODS : During a trial of second trimester and intrapartum antibiotics compared with placebo to prevent chorioamnionitis and reduce preterm birth and mother-to-child transmission of HIV , vaginal fluid was collected before antibiotics ( 20–24 weeks ) and after treatment at 28 weeks and assayed for fetal fibronectin . Pregnancy outcomes of 2,353 women delivering liveborn singleton infants are presented . RESULTS : Positive fetal fibronectin assays ( 50 ng/mL or more ) were detected in 4.2 % and 4.9 % of sample s at 20–24 weeks and 28 weeks . Positive fetal fibronectin assays at 28 weeks but not at 20–24 weeks were associated with lower mean birthweight ( 199 g , P<.001 ) ; lower mean gestational age ( 2 weeks , P<.001 ) ; six-fold higher rate of preterm birth less than 32 weeks ( 10.8 % compared with 1.9 % , odds ratio 6.3 , 95 % confidence interval 3.2–12.3 ) and a two-fold higher rate of preterm birth less than 37 weeks ( 38.7 compared with 22.0 % , odds ratio 2.3 , 95 % confidence interval 1.5–3.3 ) . Also , at 28 weeks , as the fetal fibronectin values increased , each of the outcomes worsened , and every test of trend was significant . An association between elevated fetal fibronectin levels and mother-to-child transmission of HIV was present at 20 to 24 weeks but not at 28 weeks . Antibiotic treatment at 20 to 24 weeks was not associated with fetal fibronectin levels at 28 weeks . CONCLUSION : In a population of predominantly HIV- infected African women , fetal fibronectin concentrations at 28 but not at 20–24 weeks were associated with increased risk of preterm birth . The associations were stronger for early preterm birth and when fetal fibronectin levels were higher . High levels of fetal fibronectin were positively associated with mother-to-child transmission of HIV at 20 –24 but not at 28 weeks . Antibiotic treatment did not influence fetal fibronectin levels . CLINICAL TRIAL REGISTRATION : www . clinical Trials.gov , NCT00021671 LEVEL OF EVIDENCE : The objective of the investigation was to test the presence of foetal fibronectin in the cervicovaginal secretion in symptomatic pregnancies and assess the possible prediction of imminent premature delivery . Prospect ively 84 pregnant women were examined who were admitted to hospital with symptoms of imminent premature delivery between the 24th and 34th week of pregnancy ( more than 20 contractions per day or a cervical score higher than the critical value for the given week of gestation ) . The secretion was collected by means of a dacron brush from the posterior labium of the portio vaginalis uteri and examined by a single-use kit FFN ( Fetal Fibronectin Membrane Immunoassay , Adeza Co. ) . From the total of 84 specimens of secretions examined for the presence of foetal fibronectin 32 were positive and 52 negative . Of 32 pregnant women with a positive test 19 women delivered within two weeks , 13 were discharged and the deliveries took place after the 36th week of pregnancy . In the group of 52 women with a negative result of the test 50 women were discharged and the deliveries occurred after the 36th week of gestation ; only two women who remained in hospital had premature deliveries within two weeks after collection of the specimen . In no patient discharged from hospital delivery occurred before the end of the 36th week of gestation . The finding of positive foetal fibronectin can be interpreted only as an increased risk of premature delivery ( positive predictive value 59.4 % ) . A negative test has a better predictive value . If the test is negative , there is a 96.1 % probability that premature delivery will not occur ( negative predictive value ) OBJECTIVE A preliminary study to examine the value of a rapid fetal fibronectin swab-test used as a bedside test in the prognosis of preterm labor . STUDY DESIGN Women presenting with preterm labor and intact membranes and less than 3 cm dilated were enrolled in a single referral center . Cervicovaginal swabs were assessed for the presence or absence of fetal fibronectin by means of a rapid monoclonal antibody assay the positivity of which was revealed by a colorimetric reaction . Results were compared with uterine contractions frequency , Bishop cervical score , duration of tocolysis and interval to delivery . The predictive value of fetal fibronectin test for delivery within 7 , 14 or 21 days from sampling and before 32 and 37 weeks ' of gestation was assessed in the two groups . RESULTS Among 124 eligible patients , 19 presented with a positive fibronectin test and 105 with a negative one . Gestational age at sampling , Bishop cervical score and duration of tocolysis were identical in the two groups . The number of contractions was significantly lower and gestational age at delivery was significantly higher in the fibronectin negative group . Fetal fibronectin in cervicovaginal secretions has a high sensitivity ( 89 % ) for delivery within 7 days . Absence of fetal fibronectin in cervicovaginal secretions of patients presenting with uterine contractions could rule out preterm labor within 7 and 14 days with a predictive value of 99 and 95.2 % , respectively . In negative fetal fibronectin patients , preterm delivery before 32 and 37 weeks ' is unlikely to occur with a predictive value of 97 and 85 % , respectively . CONCLUSION Cervicovaginal fetal fibronectin detected by a rapid bedside swab-test in women with symptoms of preterm labor compares favourably with quantitative assays and could prove useful in the management of preterm labor . This should be confirmed in a longer prospect i ve study OBJECTIVE The purpose of this study was to estimate the effect of sonographic cervical length ( CL ) and fetal fibronectin ( FFN ) on length of evaluation and outcomes in women with preterm labor ( PTL ) . STUDY DESIGN Women with threatened PTL were r and omized to either a knowledge group ( results of CL and FFN available and used according to study protocol ) , or a st and ard group ( blinded to CL and FFN ) . Primary outcome was length of evaluation in triage . RESULTS One hundred women were r and omized . There was no significant difference between groups in length of evaluation , but in women with CL > or = 30 mm , the mean time for evaluation was significantly shorter in the knowledge group ( 1:58 h + /- 0:50 vs 2:53 h + /- 0:50 , P = .004 ) . Incidence of spontaneous preterm birth ( SPTB ) in the knowledge group was significantly reduced ( 13.0 vs 36.2 % , P = .01 ) . CONCLUSION The knowledge of CL and FFN was associated with reduction in length of evaluation in women with CL > or = 30 mm and in incidence of SPTB in all women with PTL OBJECTIVE Our purpose was to assess the utility of cervicovaginal expression of fetal fibronectin in the diagnosis of preterm labor . STUDY DESIGN Women seen between 24 and 34 weeks ' gestation with symptoms of preterm labor , intact membranes , and cervical dilatation < 3 cm were enrolled at five university medical centers . Cervicovaginal swabs were obtained and assayed for the presence of fetal fibronectin by means of a monoclonal antibody assay . Results were compared with cervical dilatation and uterine contraction frequency as indicators of interval to delivery and delivery before 37 weeks . RESULTS A total of 192 eligible women at a mean gestational age of 30.8 + /- 2.9 weeks were enrolled from a population of 418 subjects screened . The rate of preterm birth was 32.3 % ( 62/192 ) . The mean interval from presentation to delivery was 25.3 + /- 24.1 days in the 45 subjects with a positive fibronectin assay and 52.4 + /- 24.8 days in the 147 subjects with a negative assay ( p = 0.0001 ) . The sensitivity , specificity , and positive and negative predictive values of fetal fibronectin expression for delivery < 37 weeks were 44 % ( 27/62 ) , 86 % ( 112/130 ) , 60 % ( 27/45 ) , and 76 % ( 112/147 ) . The fetal fibronectin assay was especially useful in predicting risk of delivery within 7 days ( sensitivity 93 % [ 13/14 ] , specificity 82 % [ 146/178 ] , positive predictive value 29 % [ 13/45 ] , and negative predictive value 99 % [ 146/147 ] ) and was notably superior to both cervical dilatation > 1 cm and contraction frequency greater than or equal to eight per hour ( sensitivities 29 % and 42 % , specificities 82 % and 67 % , positive predictive values 11 % and 9 % , and negative predictive values 94 % and 94 % , respectively . CONCLUSION Cervicovaginal fetal fibronectin predicts delivery within 7 days more accurately than do cervical dilatation and contraction frequency in a population of women evaluated for early preterm labor OBJECTIVE We evaluated fetal fibronectin levels for the diagnosis of preterm labor . MATERIAL AND METHODS We included 74 r and omized patients who were admitted with the diagnosis of preterm labor . Cervical and vaginal fluid sample s were washed in buffer solution prior to the introduction of a reactive strip . Results were interpreted after 10 sec. Patients with negative tests were admitted and followed up . Patients who tested positive were treated according to the protocol s of each hospital . Finally , the specificity , sensitivity , predictive value , and odds ratio were determined . RESULTS Results showed specificity , 90 % ; sensitivity , 70 % ; positive predictive value , 64 % ; negative predictive value , 78 % ; and odds ratio , 22 ; 50 % were first pregnancies with gestational ages between 22 and 34 weeks . CONCLUSIONS We consider that a positive fibronectin test is a useful , low-cost , and reliable tool for diagnosing preterm labor Objectives . To determine vaginal fetal fibronectin in women with pregnancies complicated by preterm labor ( PTL ) , preterm premature rupture of the membranes ( PPROM ) or bleeding ; to investigate possible relationships to the vaginal microflora ; and to assess the ability to predict preterm delivery from these measures OBJECTIVE Our purpose was to compare the predictive values for preterm delivery of fetal fibronectin and cervical length measured by transvaginal ultrasonography and to determine whether performing both tests improves their separate predictive values . STUDY DESIGN This prospect i ve blinded study performed both tests on 76 patients hospitalized with signs of premature labor between 24 and 34 weeks of gestation . The outcome measure was delivery before 37 weeks ' gestation . RESULTS The rate of preterm bith was 26.3 % ( 20/76 ) . The predictive values of fetal fibronectin and of a cervical length of < or = 26 mm , considered separately , were approximately equal , and the negative predictive value of each was excellent ( 86.6 % and 89.1 % , respectively ) . This value improved slightly when positive fetal fibronectin , a cervical length < or = 26 mm , or both defined abnormality ( negative predictive value 94.4 % ) . The positive predictive values , although less helpful , were still useful ( 45.2 % and 50.0 % , respectively ) . Combining both indicators did not noticeably improve the positive predictive value ( 52.4 % ) . The risk of preterm delivery for a patient with a positive fetal fibronectin level and a short cervix was high ( odds ratio 13.9 , 95 % confidence interval 3.7 to 52.2 ) . CONCLUSION Fetal fibronectin and cervical length are approximately equivalent in their ability to distinguish between patients at high and low risk for preterm delivery . For physicians equipped to perform transvaginal ultrasonography , however , the additional information about the fibronectin level provides only slight benefits BACKGROUND Preterm delivery is the leading cause of neonatal mortality in the United States , but efforts to address the problem are hampered by the inability to predict accurately which pregnancies are at risk . We postulated that damage to the fetal membranes may release fetal fibronectin into the cervix and vagina , giving rise to a biochemical marker for preterm delivery . METHODS We measured fetal-fibronectin concentrations in cervical and vaginal secretions , amniotic fluid , and maternal plasma with a sensitive immunoassay using the monoclonal antibody FDC-6 . Immunohistochemical studies were used to determine the distribution of fetal fibronectin in the placenta and amniochorionic membranes and to ascertain its cell of origin . RESULTS Women with uncomplicated pregnancies ( n = 163 ) who delivered at term rarely had cervicovaginal fetal-fibronectin concentrations above 0.05 micrograms per milliliter between 21 and 37 weeks of gestation ( 11 of 267 cervical sample s [ 4 percent ] and 9 of 267 vaginal sample s [ 3 percent ] . High levels of fetal fibronectin were detected in amniotic fluid and in the cervical or vaginal secretions of 93.8 percent of the women with preterm rupture of membranes ( n = 65 ) . Cervical or vaginal fetal fibronectin was also present in 50.4 percent of the women with preterm uterine contractions and intact membranes ( n = 117 ) , and its presence identified the women who delivered before term ( n = 60 ) with a sensitivity of 81.7 percent and a specificity of 82.5 percent . In the placenta and membranes , fetal fibronectin was found at points of contact with the uterine wall . CONCLUSIONS The presence of cervicovaginal fetal fibronectin in the second and third trimesters of pregnancy identifies a subgroup of women who are at high risk for preterm delivery . This phenomenon may reflect the separation of the chorion from the decidual layer of the uterus , with the release of intact or de grade d chorionic components of the extracellular matrix into the cervical and vaginal secretions OBJECTIVE This study was conducted to evaluate the usefulness of testing for fetal fibronectin ( fFN ) to rule out the diagnosis of preterm labour in symptomatic patients in a Canadian setting . METHODS This was a prospect i ve , blinded clinical evaluation of fFN testing in women presenting with threatened preterm labour at between 24 and 34 weeks ' gestation at two Canadian tertiary care centres . RESULTS Of the 149 women tested , 32 had a positive fFN test . In the total patient population , 10.1 % delivered within seven days of testing , and 18.2 % delivered prior to 34 weeks . A negative fFN result was associated with a 97.4 % likelihood of delivering more than seven days after testing and with a 91.4 % chance of delivering after 34 weeks . CONCLUSION The fFN test appears to provide useful information in the risk assessment of Canadian women presenting with symptoms compatible with preterm labour . A negative test has a high predictive value for delivering more than seven days after presentation Background At present , women with threatened preterm labor before 32 weeks of gestation are , after transfer to a perinatal center , treated with tocolytics and corticosteroids . Many of these women are treated unnecessarily . Fibronectin is an accurate predictor for the occurrence of preterm birth among women with threatened preterm labor . We will assess whether triage of these women with fibronectin testing , cervical length or their combination is cost-effective . Methods / Design We will investigate a prospect i ve cohort of women referred to a perinatal centre for spontaneous threatened preterm labor between 24 and 34 weeks with intact membranes . All women will be tested for fibronectin and cervical length . Women with a cervical length < 10 mm and women with a cervical length between 10 - 30 mm in combination with a positive fibronectin test will be treated with tocolytics according to local protocol . Women with a cervical length between 10 - 30 mm in combination with a negative fibronectin test will be r and omised between treatment with nifedipine ( intervention ) and placebo ( control ) for 48 hours . Women with a cervical length > 30 mm will be managed according to local protocol . Corticosteroids may be given to all women at the discretion of the attending physician . Primary outcome measure will be delivery within 7 days . Secondary outcome measures will be neonatal morbidity and mortality , complications of tocolytics , costs and health related quality of life . The analysis will be according to the intention to treat principle . We anticipate the probability on preterm birth within 7 days in the group of women with a negative fibronectine test to be 5 % . Two groups of 110 women will be needed to assure that in case of non-inferiority the difference in the proportion of preterm deliveries < 7 days will be within a prespecified boundary of 7.5 % ( one sided test , β 0.2 , α 0.05 ) . Data obtained from women with a positive and negative fibronectin tests in both the cohort study and the trial will be integrated in a cost-effectiveness analysis that will assess economic consequences of the use of fibronectin . Discussion This study will provide evidence for the use of fibronectin testing as safe and cost-effective method in a triage for threatened preterm labor . Trial registration Nederl and s Trial Register ( NTR ) number 1857 , http://www.trialregister.nl |
1,608 | 27,903,488 | Results Website studies demonstrated significant improvements in perceived usefulness and perceived ease of use , but not for knowledge , reducing barriers , and intention to use clinical practice guidelines .
Computer software studies demonstrated significant improvements in perceived usefulness , but not for knowledge and skills .
Web-based workshop and email studies demonstrated significant improvements in knowledge , perceived usefulness , and skills .
An electronic educational game intervention demonstrated a significant improvement from baseline in knowledge after 12 and 24 weeks .
Computerized decision support system studies demonstrated variable findings for improvement in skills .
Multifaceted interventions demonstrated significant improvements in beliefs about capabilities , perceived usefulness , and intention to use clinical practice guidelines , but variable findings for improvements in skills .
Most multifaceted studies demonstrated significant improvements in knowledge .
Conclusions The findings suggest that health professionals ’ perceived usability and practice behavior change vary by type of information and communication technology .
Heterogeneity and the paucity of properly conducted studies did not allow for a clear comparison between studies and a conclusion on the effectiveness of information and communication technologies as a knowledge translation strategy for the dissemination of clinical practice guidelines | Background The transfer of research knowledge into clinical practice can be a continuous challenge for research ers .
Information and communication technologies , such as websites and email , have emerged as popular tools for the dissemination of evidence to health professionals .
Objective The objective of this systematic review was to identify research on health professionals ’ perceived usability and practice behavior change of information and communication technologies for the dissemination of clinical practice guidelines . | OBJECTIVES Despite studies that show improvements in both st and ards of care and outcomes with the judicious application of clinical practice guidelines ( CPGs ) , their clinical utilization remains low . This r and omized controlled trial examined the use of a wirelessly networked mobile computer ( MC ) by physicians at the bedside with access to an emergency department information system , decision support tools ( DSTs ) , and other software options . METHODS Each of ten volunteer emergency physicians was r and omized using a matched-pair design to work five shifts in st and ard fashion ( desktop computer [ DC ] access ) and five shifts with a wirelessly networked MC . Work pattern issues and electronic CPG/DST use were compared using end-of-shift satisfaction question naires and review of a CPG/DST data base . Repeated- measures analysis of variance was used to examine between-shift differences . RESULTS A total of 100 eight-hour shifts were evaluated ; 99 % compliance with postshift question naires was achieved . Using a seven-point Likert scale ( MC values first ) , MCs were rated as being as fast ( 5.04 vs. 4.54 ; p=0.13 ) and convenient ( 5.08 vs. 4.14 ; p=0.07 ) as DCs . Overall , physicians rated MCs to be less efficient ( 3.18 vs. 4.30 ; p=0.02 ) but encouraged more frequent use of DSTs ( 4.10 vs. 3.47 ; p=0.03 ) without impacting doctor-patient communication ( 2.78 vs. 2.96 ; p=0.51 ) . During the study period , physician use of an intranet Web application ( eCPG ) was more frequent during shifts assigned to the MC when compared with the DC ( eCPG uses/shift , 3.6 vs. 2.0 ; p=0.033 ) . CONCLUSIONS The MC technology permitted physicians to access information at the bedside and increased the use of CPG/DST tools . According to physicians , patients appeared to accept their use of information technology to assist in decision making . Development of improved computer technology may address the major limitation of MC portability OBJECTIVE : To determine the effectiveness of a quality improvement program to improve pediatricians ' adherence to existing , evidence -based , attention-deficit/hyperactivity disorder ( ADHD ) practice guidelines . METHODS : Forty-nine community-based pediatricians at 8 practice s participated in a cluster-r and omized trial . Practice s were matched according to the numbers of pediatricians and the proportions of patients receiving Medicaid . The medical charts for a r and om sample of patients with ADHD for each of the participating pediatricians were examined at baseline and 6 months . All practice s participated in 4 sessions of training , including didactic lectures and office flow modification workshops . Practice s were then given access to an ADHD Internet portal that allowed parents , teachers , and pediatricians to input information ( eg , rating scales ) about patients , after which information was scored , interpreted , and formatted in a report style that was helpful for assessment and treatment of patients with ADHD . Physicians evaluated their practice behaviors quarterly and addressed underperforming areas . RESULTS : Pediatricians in the intervention group , compared with those in the control group , demonstrated significantly higher rates of many American Academy of Pediatrics – recommended ADHD care practice s , including collection of parent ( Cohen 's d = 0.69 ) and teacher ( d = 0.68 ) rating scales for assessment of children with ADHD , use of Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria ( d = 0.85 ) , and use of teacher rating scales to monitor treatment responses ( d = 1.01 ) . CONCLUSION : A quality improvement intervention that can be widely disseminated by using Internet-based information technology significantly improved the quality of ADHD care in community-based pediatric setting Background Research to assess the effect of interventions to improve the processes of shared decision making and self-management directed at health care professionals is limited . Using the protocol of Intervention Mapping , a Web-based intervention directed at health care professionals was developed to complement and optimize health services in patient-centered care . Objective The objective of the Web-based intervention was to increase health care professionals ’ intention and encouraging behavior toward patient self-management , following cardiovascular risk management guidelines . Methods A r and omized controlled trial was used to assess the effect of a theory-based intervention , using a pre-test and post-test design . The intervention website consisted of a module to help improve professionals ’ behavior , a module to increase patients ’ intention and risk-reduction behavior toward cardiovascular risk , and a parallel module with a support system for the health care professionals . Health care professionals ( n=69 ) were recruited online and r and omly allocated to the intervention group ( n=26 ) or ( waiting list ) control group ( n=43 ) , and invited their patients to participate . The outcome was improved professional behavior toward health education , and was self-assessed through question naires based on the Theory of Planned Behavior . Social-cognitive determinants , intention and behavior were measured pre-intervention and at 1-year follow-up . Results The module to improve professionals ’ behavior was used by 45 % ( 19/42 ) of the health care professionals in the intervention group . The module to support the health professional in encouraging behavior toward patients was used by 48 % ( 20/42 ) . The module to improve patients ’ risk-reduction behavior was provided to 44 % ( 24/54 ) of patients . In 1 of every 5 patients , the guideline for cardiovascular risk management was used . The Web-based intervention was poorly used . In the intervention group , no differences in social-cognitive determinants , intention and behavior were found for health care professionals , compared with the control group . We narrowed the intervention group and no significant differences were found in intention and behavior , except for barriers . Results showed a significant overall difference in barriers between the intervention and the control group ( F 1=4.128 , P=.02 ) . Conclusions The intervention was used by less than half of the participants and did not improve health care professionals ’ and patients ’ cardiovascular risk-reduction behavior . The website was not used intensively because of time and organizational constraints . Professionals in the intervention group experienced higher levels of barriers to encouraging patients , than professionals in the control group . No improvements were detected in the processes of shared decision making and patient self-management . Although participant education level was relatively high and the intervention was pre-tested , it is possible that the way the information was presented could be the reason for low participation and high dropout . Further research embedded in professionals ’ regular consultations with patients is required with specific emphasis on the processes of dissemination and implementation of innovations in patient-centered care . Trial Registration Netherl and s Trial Register Number ( NTR ) : NTR2584 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=2584 ( Archived by WebCite at http://www.webcitation.org/6STirC66r ) CONTEXT Despite evidence that a variety of continuing medical education ( CME ) techniques can foster physician behavioral change , there have been no r and omized trials comparing performance outcomes for physicians participating in Internet-based CME with physicians participating in a live CME intervention using approaches documented to be effective . OBJECTIVE To determine if Internet-based CME can produce changes comparable to those produced via live , small-group , interactive CME with respect to physician knowledge and behaviors that have an impact on patient care . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted from August 2001 to July 2002 . Participants were 97 primary care physicians drawn from 21 practice sites in Houston , Tex , including 7 community health centers and 14 private group practice s. A control group of 18 physicians from these same sites received no intervention . INTERVENTIONS Physicians were r and omly assigned to an Internet-based CME intervention that could be completed in multiple sessions over 2 weeks , or to a single live , small-group , interactive CME workshop . Both incorporated similar multifaceted instructional approaches demonstrated to be effective in live setting s. Content was based on the National Institutes of Health National Cholesterol Education Program -- Adult Treatment Panel III guidelines . MAIN OUTCOME MEASURES Knowledge was assessed immediately before the intervention , immediately after the intervention , and 12 weeks later . The percentage of high-risk patients who had appropriate lipid panel screening and pharmacotherapeutic treatment according to guidelines was documented with chart audits conducted over a 5-month period before intervention and a 5-month period after intervention . RESULTS Both interventions produced similar and significant immediate and 12-week knowledge gains , representing large increases in percentage of items correct ( pretest to posttest : 31.0 % [ 95 % confidence interval { CI } , 27.0%-35.0 % ] ; pretest to 12 weeks : 36.4 % [ 95 % CI , 32.2%-40.6 % ] ; P<.001 for all comparisons ) . Chart audits revealed high baseline screening rates in all study groups ( > or = 93 % ) with no significant postintervention change . However , the Internet-based intervention was associated with a significant increase in the percentage of high-risk patients treated with pharmacotherapeutics according to guidelines ( preintervention , 85.3 % ; postintervention , 90.3 % ; P = .04 ) . CONCLUSIONS Appropriately design ed , evidence -based online CME can produce objective ly measured changes in behavior as well as sustained gains in knowledge that are comparable or superior to those realized from effective live activities The purpose of this r and omized , controlled , home care intervention was to test the effectiveness of two nurse-targeted , e-mail-based interventions to increase home care nurses ' adherence to pain assessment and management guidelines , and to improve patient outcomes . Nurses from a large urban non-profit home care organization were assigned to usual care or one of two interventions upon identification of an eligible cancer patient with pain . The basic intervention consisted of a patient-specific , one-time e-mail reminder highlighting six pain-specific clinical recommendations . The augmented intervention supplemented the initial e-mail reminder with provider prompts , patient education material , and clinical nurse specialist outreach . Over 300 nurses were r and omized and outcomes of 673 of their patients were review ed . Data collection involved clinical record abstract ion of nurse care practice s and patient interviews completed approximately 45 days after start of care . The intervention had limited effect on nurse-documented care practice s but patient outcomes were positively influenced . Patients in the augmented group improved significantly over the control group in ratings of pain intensity at its worst , whereas patients in the basic group had better ratings of pain intensity on average . Other outcomes measures were also positively influenced but did not reach statistical significance . Our findings suggest that although reminders have some role in improving cancer pain management , a more intensive approach is needed for a generalized nursing workforce with limited recent exposure to state-of-the-art pain management practice OBJECTIVE To investigate the effectiveness of an Inpatient Diabetes Management Program ( IDMP ) on physician knowledge and inpatient glycemic control . METHODS Residents assigned to General Internal Medicine inpatient services were r and omized to receive the IDMP ( IDMP group ) or usual education only ( non-IDMP group ) . Both groups received an overview of inpatient diabetes management in conjunction with reminders of existing order sets on the hospital Web site . The IDMP group received print copies of the program and access to an electronic version for a personal digital assistant ( PDA ) . A Diabetes Knowledge Test ( DKT ) was administered at baseline and at the end of the 1-month rotation . The frequency of hyperglycemia among patients under surveillance by each group was compared by using capillary blood glucose values and a dispersion index of glycemic variability . IDMP users completed a question naire related to the program . RESULTS Twenty-two residents participated ( 11 in the IDMP group and 11 in the non-IDMP group ) . Overall Diabetes Knowledge Test scores improved in both groups ( IDMP : 69 % ± 1.7 % versus 83 % ± 2.1 % , P = .003 ; non-IDMP : 76 % ± 1.2 % versus 84 % ± 1.4 % , P = .02 ) . The percentage of correct responses for management of corticosteroid-associated hyperglycemia ( P = .004 ) and preoperative glycemic management ( P = .006 ) improved in only the IDMP group . The frequency of hyperglycemia ( blood glucose level > 180 mg/dL ) and the dispersion index ( 5.3 ± 7.6 versus 3.7 ± 5.6 ; P = .2 ) were similar between the 2 groups . CONCLUSION An IDMP was effective at improving physician knowledge for managing hyperglycemia in hospitalized patients treated with corticosteroids or in preparation for surgical procedures . Educational programs directed at improving overall health care provider knowledge for inpatient glycemic management may be beneficial ; however , improvements in knowledge do not necessarily result in improved glycemic outcomes Background Clinical practice guidelines are important for transmitting research findings into practice and facilitating the application of evidence -based practice ( EBP ) . There is a paucity of knowledge about the impact of guideline implementation strategies in primary care physical therapy . The aim of this study was to evaluate the effect of a guideline implementation intervention in primary care physical therapy in western Sweden . Methods An implementation strategy based on theory and current evidence was developed . A tailored , multi-component implementation intervention , addressing earlier identified determinants , was carried out in three areas comprising 28 physical therapy practice s including 277 physical therapists ( PTs ) ( intervention group ) . In two adjacent areas , 171 PTs at 32 practice s received no intervention ( control group ) . The core component of the intervention was an implementation seminar with group discussion s. Among other components were a website and email reminders . Data were collected at baseline and follow-up with a web-based question naire . Primary outcomes were the self-reported awareness of , knowledge of , access to , and use of guidelines . Secondary outcomes were self-reported attitudes toward EBP and guidelines . Analyses were performed using Pearson ’s χ2 test and approximative z-test . Results 168 PTs ( 60.6 % ) in the intervention group and 88 PTs ( 51.5 % ) in the control group responded to the follow-up question naire . 186/277 PTs ( 67.1 % ) participated in the implementation seminars , of which 97 ( 52.2 % ) responded . The proportions of PTs reporting awareness of ( absolute difference in change 20.6 % , p = 0.023 ) , knowledge where to find ( 20.4 % , p = 0.007 ) , access to ( 21.7 % , p < 0.001 ) , and frequent use of ( 9.5 % , NS ) guidelines increased more in the intervention group than in the control group . The proportion of PTs reporting frequent guideline use after participation in the implementation seminar was 15.2 % ( p = 0.043 ) higher than the proportion in the control group . A higher proportion considered EBP helpful in decision making ( p = 0.018 ) . There were no other significant differences in secondary outcomes . Conclusions A tailored , theory- and evidence -informed , multi-component intervention for the implementation of clinical practice guidelines had a modest , positive effect on awareness of , knowledge of , access to , and use of guidelines , among PTs in primary care in western Sweden . In general , attitudes to EBP and guidelines were not affected Background Methods for the dissemination , underst and ing and implementation of clinical guidelines need to be examined for their effectiveness to help doctors integrate guidelines into practice . The objective of this r and omised controlled trial was to evaluate the effectiveness of an interactive online Diabetes Needs Assessment Tool ( DNAT ) ( which constructs an e-learning curriculum based on individually identified knowledge gaps ) , compared with self-directed e-learning of diabetes guidelines . Methods Health professionals were r and omised to a 4-month learning period and either given access to diabetes learning modules alone ( control group ) or DNAT plus learning modules ( intervention group ) . Participants completed knowledge tests before and after learning ( primary outcome ) , and surveys to assess the acceptability of the learning and changes to clinical practice ( secondary outcomes ) . Results Sixty four percent ( 677/1054 ) of participants completed both knowledge tests . The proportion of nurses ( 5.4 % ) was too small for meaningful analysis so they were excluded . For the 650 doctors completing both tests , mean ( SD ) knowledge scores increased from 47.4 % ( 12.6 ) to 66.8 % ( 11.5 ) [ intervention group ( n = 321 , 64 % ) ] and 47.3 % ( 12.9 ) to 67.8 % ( 10.8 ) [ control group ( n = 329 , 66 % ) ] , ( ANCOVA p = 0.186 ) . Both groups were satisfied with the usability and usefulness of the learning material s. Seventy seven percent ( 218/284 ) of the intervention group reported combining the DNAT with the recommended reading material s was " very useful"/"useful " . The majority in both groups ( 184/287 , 64.1 % intervention group and 206/299 , 68.9 % control group ) [ 95 % CI for the difference ( -2.8 to 12.4 ) ] reported integrating the learning into their clinical practice . Conclusions Both groups experienced a similar and significant improvement in knowledge . The learning material s were acceptable and participants incorporated the acquired knowledge into practice .Trial registration IS RCT N : IS RCT BACKGROUND Evidence -based guidelines are seen as an important instrument to transfer scientifically generated knowledge into daily clinical practice and to ensure high st and ards of clinical care . Despite wide promulgation , clinical guidelines so far have a limited impact on individual professional learning and on changing daily medical practice . OBJECTIVES Our aims were ( i ) to study a potential knowledge increase among German GPs after implementation of web- and evidence -based guidelines and ( ii ) to identify and analyse potential barriers to individual professional learning with computerized guidelines . METHODS A prospect i ve , r and omized controlled trial was conducted including 72 GPs ( 21 % female , 79 % male ) . The intervention group ( n = 38 ) had access to clinical guidelines via the Internet or CD-ROM , the control group had not ( n = 34 ) . Both groups received a st and ardized two-part question naire . An increase of knowledge was measured with 25 multiple choice questions related to four different medical topics . In addition , reasons for using or not using computerized guidelines were analysed after access to guidelines was open to all participating physicians . RESULTS There was no significant knowledge increase in the intervention group ( P = 0.69 ) . Twenty-two ( 58 % ) GPs of the intervention group had used the guidelines . Unspecified curiosity ( 76 % ) and a specific medical question ( 38 % ) were predominant motives for usage among physicians who had used the guidelines . Among ' non-users ' , 78 % stated ' lack of time ' as the main reason for not using guidelines . CONCLUSION An efficient knowledge transfer through computerized guidelines was not achieved . Usage , individual learning and potential implementation depend on adequate incentives and pragmatic aspects of clinical practice : easy and quick access Background A gap exists between evidence and practice regarding the management of cardiovascular risk factors . This gap could be narrowed if systematic ally developed clinical practice guidelines were effectively implemented in clinical practice . We evaluated the effects of a tailored intervention to support the implementation of systematic ally developed guidelines for the use of antihypertensive and cholesterol-lowering drugs for the primary prevention of cardiovascular disease . Methods and Findings We conducted a cluster-r and omized trial comparing a tailored intervention to passive dissemination of guidelines in 146 general practice s in two geographical areas in Norway . Each practice was r and omized to either the tailored intervention ( 70 practice s ; 257 physicians ) or control group ( 69 practice s ; 244 physicians ) . Patients started on medication for hypertension or hypercholesterolemia during the study period and all patients already on treatment that consulted their physician during the trial were included . A multifaceted intervention was tailored to address identified barriers to change . Key components were an educational outreach visit with audit and feedback , and computerized reminders linked to the medical record system . Pharmacists conducted the visits . Outcomes were measured for all eligible patients seen in the participating practice s during 1 y before and after the intervention . The main outcomes were the proportions of ( 1 ) first-time prescriptions for hypertension where thiazides were prescribed , ( 2 ) patients assessed for cardiovascular risk before prescribing antihypertensive or cholesterol-lowering drugs , and ( 3 ) patients treated for hypertension or hypercholesterolemia for 3 mo or more who had achieved recommended treatment goals . The intervention led to an increase in adherence to guideline recommendations on choice of antihypertensive drug . Thiazides were prescribed to 17 % of patients in the intervention group versus 11 % in the control group ( relative risk 1.94 ; 95 % confidence interval 1.49–2.49 , adjusted for baseline differences and clustering effect ) . Little or no differences were found for risk assessment prior to prescribing and for achievement of treatment goals . Conclusions Our tailored intervention had a significant impact on prescribing of antihypertensive drugs , but was ineffective in improving the quality of other aspects of managing hypertension and hypercholesterolemia in primary care BACKGROUND Traditional continuing medical education ( CME ) has not been successful in improving physicians ' practice . This project evaluated the use of e-mail to deliver evidence -based moderated case discussion s to family physicians . METHODS In a r and omized controlled trial , 58 southwestern Ontario physicians were recruited and r and omly assigned to receive two evidence -based cases ( type 2 diabetes , prevention ) or were put on a waiting list to receive the same . On-line discussion s took place about each case . Data were collected using two knowledge question naires , charts audits , and st and ardized patient visits for each of the two cases . RESULTS The two groups were similar except for rural/urban and solo versus group practice . The latter was related to outcomes , and analyses were controlled for this variable . The intervention group showed statistically significant improvements compared to the control group for knowledge and chart-audit scores for one of the two cases . CONCLUSIONS Using a r and omized control design , this e-mail CME method demonstrated mixed effectiveness Background Evidence -based clinical guidelines on contraceptive use were developed and distributed among all Flemish general practitioners ( GPs ) in Belgium . Objectives To evaluate the effectiveness of two strategies for implementing a guideline on oral contraceptives in order to enhance the quality of the first contraception consultation in general practice , by either empowering patients or by introducing a computer decision support system ( CDSS ) . Method A r and om sample of 45 GPs was distributed among three study groups . One group was visited by an ‘ empowered patient ’ , one group 's electronic medical record was supplemented with a CDSS , and one group served as the control group . Simulated patients ( SPs ) assessed the performance of GPs in daily practice before and after the interventions , using a vali date d 48-point checklist . Results The baseline mean score of the 43 GPs was 26.16 ( SD = 5.76 ) . The SPs received sufficient information about correct pill usage , but not concerning factors associated with pill failure and drug interaction . After the intervention , the GPs ' mean score was 26.39 ( SD = 6.86 ) . Only the intervention group with the ‘ empowered patient ’ scored significantly better ( 29.92 [ SD = 7.11 ] ) . The computer group and control group scored lower ( 24.36 [ SD = 6.60 ] and 24.82 [ SD = 5.65 ] , respectively ) . Conclusion Developing and distributing an evidence -based guideline did not change GPs ' behaviour . However , empowering patients to participate more proactively significantly improved GPs ' performance during a contraception consultation . A CDSS did not Introduction : The integration of new evidence into clinical practice can be a prolonged process , with delays of years or even decades . One approach to speed this integration is through the use of online provider education . Problem : Venous thromboembolism ( VTE ) is a serious patient safety issue . Prevention requires coordinated care and adherence to evidence -based guidelines , supported by provider education . Purpose : This study reports how an interdisciplinary team developed and piloted an online provider training program for the prevention of VTE . Hypothesis : If providers use the online educational training , they will demonstrate increased mastery of key content areas related to VTE prophylaxis . Methods : We used a prospect i ve test — retest study design in which medical residents and fellows served as their own controls . All participants were given a pretest followed by educational content and then a posttest . We also assessed 2 different types of learning content ( ie , with and without case studies / questions ) and r and omized participants to each type prior to assessment . Results : Using the McNemar test we found a trend for knowledge gains related to VTE guidelines on the posttest for clinicians ( n = 67 ) with a 14.5 % improvement in content mastery ( P = .05 , 2-tailed ) . We did not find any significant differences between training modalities . Clinicians overall reported high levels of satisfaction with the application . Conclusion : Our online education efforts indicate the potential for increasing mastery of VTE prophylaxis concepts . If re sources are limited , we suggest a static approach to content delivery and an exploration of st and ardized methods for portability of online curriculums across learning management systems OBJECTIVE To determine the impact of a multifaceted knowledge translation strategy for a new vaccination pain management guideline on public health immunizers ' attitudes , beliefs and use of pain-relieving strategies during childhood vaccination . METHOD Using a r and omized controlled pre-post study design , public health nurses ( PHNs ) at intervention sites received a multifaceted knowledge translation intervention about new pain management guidelines incorporated in the British Columbia Immunization Program Manual , including education , supplies and online support . Attitudes and beliefs of PHNs toward immunization pain and pain management , and use of pain-relieving strategies were compared for the intervention sites between the pre- and postimplementation phases . RESULTS A total of 516 children were immunized by 31 PHNs pre- and postimplementation in the intervention sites . Postimplementation , satisfaction and confidence with ability to manage pain and willingness to use newly recommended strategies were significantly more positive ( P<0.05 ) in the intervention sites , and overall use of at least one newly recommended strategy increased from 49.8 % preintervention to 77.6 % postimplementation ( P<0.001 ) . CONCLUSION The knowledge translation intervention improved PHN immunizers ' attitudes , beliefs and practice s regarding paediatric vaccination pain management . Reducing pain may result in a better immunization experience for children , caregivers and immunizers PURPOSE Electronic health records ( EHRs ) with clinical decision support hold promise for improving quality of care , but their impact on management of chronic conditions has been mixed . This study examined the impact of EHR-based clinical decision support on adherence to guidelines for reducing gastrointestinal complications in primary care patients on nonsteroidal anti-inflammatory drugs ( NSAIDs ) . METHODS This r and omized controlled trial was conducted in a national network of primary care offices using an EHR and focused on patients taking traditional NSAIDs who had factors associated with a high risk for gastrointestinal complications ( a history of peptic ulcer disease ; concomitant use of anticoagulants , anti-platelet medications [ including aspirin ] , or corticosteroids ; or an age of 75 years or older ) . The offices were r and omized to receive EHR-based guidelines and alerts for high-risk patients on NSAIDs , or usual care . The primary outcome was the proportion of patients who received guideline -concordant care during the 1-year study period ( June 2007–June 2008 ) , defined as having their traditional NSAID discontinued ( including a switch to a lower-risk medication ) , having a gas-troprotective medication coprescribed , or both . RESULTS Participants included 27 offices with 119 clinicians and 5,234 high-risk patients . Intervention patients were more likely than usual care patients to receive guideline -concordant care ( 25.4 % vs 22.4 % , adjusted odds ratio = 1.19 ; 95 % confidence interval , 1.01–1.42 ) . For individual high-risk groups , patients on low-dose aspirin were more likely to receive guideline -concordant care with the intervention vs usual care ( 25.0 % vs 20.8 % , adjusted odds ratio = 1.30 ; 95 % confidence interval , 1.04–1.62 ) , but there was no significant difference for patients in other high-risk groups . CONCLUSIONS This study showed only a small impact of EHR-based clinical decision support for high-risk patients on NSAIDs in primary care offices . These results add to the growing literature about the complexity of EHR-based clinical decision support for improving quality of care Clinical guidelines have been developed to assist with the management of patient care ; however , these guidelines are frequently neglected in clinical practice . Computer-generated reminders enhance guideline use , but these systems often fail to achieve high rates of guideline utilization . This study was design ed to test the hypothesis that computer-generated , individualized feedback regarding adherence to care guidelines will significantly improve clinician compliance with guideline recommendations presented through a computer-assisted management protocol . Half of the 45 primary care clinicians employed at a primary care clinic affiliated with an academic medical center , were r and omized to receive a biweekly electronic mail message consisting of a computer-generated report summarizing his/her response to care guideline recommendations for the diabetic patients seen during the previous 2 weeks . Clinician compliance with guideline recommendations was the primary outcome measure . This study demonstrated that the intervention significantly increased clinician compliance with the guideline recommendations without incurring high maintenance expenses . Median compliance among the intervention group was 35 % versus 6.1 % among the control group ( p < 0.01 ) . Electronically distributed , computer-generated , individualized feedback regarding clinician use of care guideline recommendations is an effective way to enhance compliance with a care guideline OBJECTIVE To compare the effects of computerized and paper-based versions of guidelines on recently qualified physicians ' consultation practice s. METHODS Two arm cluster r and omized controlled trial . Physicians were r and omized to receive computerized or textbook-based versions of the same guidelines for a 4-week study period . Physicians ' compliance with guideline recommendations about laboratory , radiological , physical and other examinations , procedures , nonpharmacologic and pharmacologic treatments , physiotherapy , and referrals were measured by case note review . RESULTS There were 139 recently qualified physicians working in 96 primary healthcare centers in Finl and who participated in the study . Data on 4,633 patient encounters were abstract ed , of which 3,484 were suitable for further analysis . Physicians ' compliance with guidelines was high ( over 80 % for use of laboratory , radiology , physical examinations , and referrals ) . There were no significant differences in physicians ' consultation practice s in any of the measured outcomes between the computerized and textbook group . CONCLUSION Guidelines are a useful source of information for recently qualified physicians working in primary care . However , the method of presentation of the guidelines ( electronic or paper ) does not have an effect on guideline use or their impact on decisions . Other factors should be considered when choosing the method of presentation of guidelines , such as information-seeking time , ease of use during the consultation , ability to up date , production costs , and the physician 's own preferences Objective : To determine whether Interactive Spaced Education ( ISE ) is an effective and acceptable form of graduate and continuing medical education ( GME/CME ) , using clinical practice guideline ( CPG ) education as an experimental system . Summary Background Data : ISE is a novel form of online education , which combines the pedagogical merits of the spacing and testing effects . Its efficacy for GME and CME is not known . Methods : One-hundred sixty urologists and 320 urology residents were r and omized to 1 of 2 cohorts . We developed and vali date d 48 ISE items ( questions and answers ) on 5 urology CPGs ( hematuria and priapism [ HP ] ; staghorn calculi , infertility , and antibiotic use [ SIA ] ) . Physicians were sent 3 emails a week , each containing 2 questions . Content was repeated 3 times over 20 weeks . Cohort A physicians received the 3-cycle ISE course on HP , with 24 control items on SIA in cycle 3 . Cohort B physicians received the 3-cycle ISE course on SIA , with 24 control items on HP in cycle 3 . Results : The ISE program was completed by 71 % urologists and 83 % residents . Cohort A scores on HP increased from mean 44.9 % in cycle 1 % to 75.7 % in cycle 3 , a 57 % relative increase compared with controls ( P < 0.001 ; Cohen effect size , 2.2 ) . Similarly , cohort B scores on SIA increased from 45.2 % in cycle 1 % to 69.5 % in cycle 3 , a 56 % relative increase compared with controls ( P < 0.001 ; effect size , 2.2 ) . Eighty-four percent of all participants requested to enroll in further ISE programs . Conclusions : ISE is an effective and well-accepted form of GME and CME and is a promising new methodology to improve CPG knowledge Many primary care physicians have not learned about key advances in caring for patients after acute myocardial infa rct ion , including the use of -blockers ( 1 ) and angiotensin-converting enzyme inhibitors ( 2 ) . Although professional organizations have disseminated guidelines for the care of acute myocardial infa rct ion ( 3 , 4 ) , important therapies continue to be underused ( 5 ) . Physicians read guidelines to stay up-to- date ( 6 ) , but reading without additional interaction is relatively ineffective for learning ( 7 ) and has little effect on practice ( 8) . Physicians therefore need better methods for learning from guidelines . Self- assessment tests are often used to enhance self- study of printed material s ( 9 , 10 ) , but physicians can now choose from a growing number of World Wide Web sites that offer on-line self- study ( 11 ) . Since the 1960s , computer-assisted instruction has been explored as a method for medical education ( 12 - 15 ) . In theory , computer-assisted instruction can enhance self- study by tailoring presentations to learners ' individual needs and by including interactive simulations ( 16 ) . Two previous studies comparing computer-assisted instruction systems with carefully constructed self- study controls found mixed results ( 17 , 18 ) . In both of these studies , the systems were developed for and tested among medical students before the advent of the Web . Therefore , physicians have little direct evidence to inform their choices among currently available self- study methods . We conducted a r and omized trial to compare the educational outcomes produced by a Web-based tutorial on myocardial infa rct ion guidelines with those produced by self- assessment based and study from print versions of the same guidelines . We hypothesized that print-based self- study would result in substantial learning but Web-based self- study would produce incrementally greater knowledge gains , retention , learning efficiency , and satisfaction . We conducted this trial among residents rather than community physicians because residents frequently use self- study material s and because we anticipated that they would be more feasible to recruit . Methods Design of Self- Study Alternatives Guidelines and Learning Objectives The American College of Cardiology ( ACC ) , the American Heart Association ( AHA ) , and the American College of PhysiciansAmerican Society of Internal Medicine ( ACPASIM ) allowed us to use their guidelines for this trial . We wrote 20 cognitive learning objectives ( 19 ) , covering knowledge from one or both guidelines that would be important for physicians who provide primary care to patients after myocardial infa rct ion . One of the authors , an expert in evidence -based cardiology , edited the objectives for content validity and importance . The final set of learning objectives is shown in the Appendix Table . Knowledge Tests We wrote multiple-choice questions that had one correct response demonstrating the knowledge in a single learning objective . Thirty attending physicians and fellows in internal medicine , family medicine , and cardiology critiqued the clarity and difficulty of prospect i ve questions by using an electronic mail quiz system that tracked each question 's average score ( 20 ) . These data were used to assemble a 20- question pretest and a different 20- question post-test . The tests included one question per learning objective and were approximately equivalent in overall difficulty . Expected scores on the final pretest and post-test differed by less than 6 % . For each question on the final test forms , participants could place a check mark next to the statement , I would like to review available evidence or recommendations on this topic . We referred to this feature as the review flag . For both of the self- study alternatives in this trial , learners initially completed the pretest on paper . Web-Based Self- Study Material s We constructed a Web-based learning system called SAGE ( Self- Study Acceleration with Graphic Evidence ) . Participants who used SAGE copied their pretest answers into the system and were then taken to the main tutorial page , which presents an overview of the user 's pretest results for each learning objective . By clicking on hyperlinks , users could view a sequence of learning re sources for each objective . The first re source for each objective was the relevant pretest answer . From there , users could click on hyperlinks to view the relevant guideline passages ( highlighted segments of text in an on-line version of the complete guideline document ) . When guidelines referred to l and mark clinical trials , users could click on a link to open a graphic evidence browser ( Figure 1 ) . Complete instructions for using SAGE were provided in the system . The program was intended to combine two strategies of computer-assisted instruction : a tutorial strategy , which focuses the learner on deficits in previous knowledge , and a simulation strategy , which reinforces knowledge through interaction with graphic models of r and omized trial evidence . We wrote software for SAGE in Server-side JavaScript , using the Netscape Enterprise Server ( Mountain View , California ) running on a Sun Ultrasparc2 workstation ( Mountain View , California ) . For animated statistical graphics , we wrote a Java applet . Figure 1 . The SAGE ( Self- Study Acceleration with Graphic Evidence ) r and omized trial viewer . Printed Self- Study Material s Printed material s for the control group included the same self- assessment test and guidelines as the Web-based material s. The printed material s included 1 ) a booklet showing the correct answer for each pretest question and the learning objective each question was intended to evaluate and 2 ) complete reprints of the ACPASIM and ACC/AHA guidelines . Learners were instructed to compare their pretest answers with the correct answers and look up the evidence or guideline recommendations for each learning objective that they may not have met by using the outline structure of the ACPASIM guidelines and the index of the ACC/AHA guidelines . Material s in the control group were intended to provide learning through self- assessment and study from the actual guideline documents as distributed by the specialty societies . The control material s contained the same pretest answers and guideline content as SAGE but lacked the hypermedia navigation features and the detailed , interactive , graphic presentations of l and mark trial evidence . Of note , however , the guideline material s for both self- study groups contained all of the information that learners would need to meet each learning objective , including narrative descriptions of the key trial results that were available graphically in SAGE . Study Sample We recruited residency programs in family and internal medicine at four universities . Approval for research involving humans was obtained from each university 's institutional review board . A total of 5 family medicine and 7 internal medicine programs agreed to participate . We recorded the name , sex , and training year of every resident across all 12 programs in a confidential recruitment data base . Letters were placed in residents ' mailboxes inviting them to attend a 1.25-hour learning session in which they would be r and omly assigned to study from computer or printed material s on the care of myocardial infa rct ion . An honorarium of $ 30 was offered for completing the trial . The trial was also announced at resident conferences . All residents who attended a session and gave consent became eligible participants . Self- Study Sessions Participants used the self- study material s in a single session that began with the pretest and ended with an immediate post-test . After completing the pretest , participants kept carbon copies of their answers , returned their originals , and received their r and omly generated study group assignment . Those assigned to the control group were given the printed material s , and those assigned to SAGE went to an adjacent computer classroom , where they logged on and entered their pretest answers . Participants in both groups were asked to study until they felt that they had met the learning objectives , at which point the self- study material s were removed and they immediately took the post-test on paper . Each session was proctored to ensure that all learning was attributable to self- study from the assigned material without use of extraneous material s or discussion with colleagues . No irregularities occurred . Participants could not attend more than one session and were not allowed to keep the printed self- study material s or to access SAGE after completing their session . Study Group Assignment Individual participants were r and omly assigned to study groups by a computer program that generated blocked r and omization stratified by the participants ' sex and residency year . As each resident arrived at a session , he or she was registered on a laptop computer that contained coded records from the recruitment data base . As the first participants finished the pretest , a r and omization program run on the laptop generated a balanced pool of assignments for each sexresidency year category ( using a block size of 2 [ 21 ] ) . For each registered participant , the program chose an assignment at r and om from the appropriate pool . As participants turned in their pretests , they and the investigators looked up their assignments on the laptop screen . Study group assignment was therefore simultaneously revealed to the participants and to the investigators . Outcome Measures Knowledge scores from multiple-choice tests were calculated by assigning 1 point per correct answer ; unanswered items were considered incorrect . This created scores that could range from 0 to 20 points . The primary outcome of the trial was knowledge on the immediate post-test . The time spent study ing was measured by using a time-stamp machine for participants in the control group and the server log for participants in the SAGE group . Learning efficiency was calculated as the point gain from pretest to immediate post-test divided by the Objective : To assess the utility of an abbreviated teaching tool ( ATT ) in improving emergency medicine pediatricians ' knowledge of the diagnosis and the treatment of pelvic inflammatory disease ( PID ) . Methods : An 18- question internet-based survey , which included questions about the diagnosis and the treatment of PID , was administered to members of the American Academy of Pediatrics Section on Emergency Medicine . Participants were r and omized to receive either a weblink to the Centers for Disease Control and Prevention ( CDC ) sexually transmitted disease treatment guidelines ( weblink group ) or a 1-page ATT that summarized the CDC guidelines ( ATT group ) to assist with completion of the survey . We compared the accuracy of responses between the 2 groups . Results : Two hundred thirty-seven subjects responded to the survey ( 109 from the weblink group and 128 from ATT group ) . There were no significant differences between the groups with respect to sex , geographic location , practice setting , years of experience , or reported frequency of recent PID diagnoses . Ninety-seven percent of the ATT group correctly identified the appropriate antibiotic regimen in compliance with the CDC guidelines compared with 61 % of the weblink group ( OR , 19.4 ; 95 % confidence interval , 6.6 - 76.9 ) ; the ATT group was also more likely to correctly identify appropriate treatment options overall ( OR , 9.6 ; 95 % confidence interval , 4.9 - 19.3 ) . Conclusions : Although the overall PID knowledge in our sample was low , the physicians with access to a 1-page teaching tool summarizing the CDC treatment recommendations for PID performed significantly better when asked questions involving PID treatment as compared with providers with access to the CDC Web site . Further studies should investigate whether access to a similar tool can improve patient care |
1,609 | 29,611,180 | Antibiotic antimicrobial and combined ( antibiotic-non antibiotic ) lock solutions decreased the incidence of CRI compared to control lock solutions , whereas non-antibiotic lock solutions reduce CRI only for tunnelled CVC .
The effect on thrombosis incidence is uncertain for all antimicrobial lock solutions . | BACKGROUND Patients undergoing haemodialysis ( HD ) through a central venous catheter ( CVC ) are exposed to several risks , being a catheter-related infection ( CRI ) and a CVC lumen thrombosis among the most serious .
St and ard of care regarding CVCs includes their sealing with heparin lock solutions to prevent catheter lumen thrombosis .
Other lock solutions to prevent CRI , such as antimicrobial lock solutions , have proven useful with antibiotics solutions , but not as yet for non-antibiotic antimicrobial solutions .
Furthermore , it is uncertain if these solutions have a negative effect on thrombosis incidence .
OBJECTIVES To assess the efficacy and safety of antimicrobial ( antibiotic , non-antibiotic , or both ) catheter lock solutions for preventing CRI in participants undergoing HD with a CVC . | BACKGROUND Catheter-restricted antibiotic lock solutions were found to be effective in the prevention of catheter-related bacteremia ( CRB ) , but insufficient data are available about the ideal agent and dose . We hypothesized that a low concentration of gentamicin would be as effective as the high doses studied in the past . METHODS In this prospect i ve , open-labeled , r and omized , clinical trial of patients on long-term hemodialysis therapy , patients were r and omly assigned to administration of an antibiotic lock solution of gentamicin/citrate ( 4 mg/mL ) , minocycline/EDTA , or the control solution of heparin . Patients were followed up until the study end point of CRB was reached or a censoring event occurred . Interim data analysis was performed after 6 months to assess data safety ; efficacy was noted and the study was terminated early . RESULTS Sixty-two patients were enrolled into the study , evenly distributed in 3 arms , with data from 1 patient excluded from analysis . Seven of 20 patients in the heparin group ( 4.0 events/1,000 catheter days ) , 1 of 21 patients in the minocycline group ( 0.4 events/1,000 catheter days ) , and none of 20 patients in the gentamicin group developed bacteremia . Results were statistically significant by using 2-tailed Fisher exact test ; heparin versus gentamicin , P = 0.008 , and heparin versus minocycline , P = 0.020 . CONCLUSION Antibiotic lock solutions are superior to the st and ard heparin lock alone in the prevention of CRBs , and low-dose gentamicin solution has efficacy similar to that of greater concentrations used in previous studies INTRODUCTION Catheter-related infection is associated with increased all-cause mortality and morbidity in hemodialysis patients . This study aim ed to evaluate an antimicrobial lock solution ( cloxacillin and heparin ) in temporary noncuffed double-lumen catheters for long-term intermittent hemodialysis as a method of preventing catheter-related infection . MATERIAL S AND METHODS Patients on hemodialysis with noncuffed temporary double lumen catheter were r and omly divided into 2 groups . Fifty patients received a solution containing cloxacillin , 100 mg/mL , plus heparin , 1000 IU/mL as a 2.5-mL solution instilled in each of catheter lumens after dialysis session . Another 50 patients received only heparin . They were allowed to dwell until the next session of dialysis . RESULTS One catheter-related bacteremia was observed in the antibiotic group whereas catheter-related bacteremia was observed in 8 of those who received heparin only . The rate of catheter-related bacteremia episodes were 0.5 per 1000 catheter-days in the antibiotic group versus 7.8 per 1000 catheter-days in the control group ( P = .02 ) . CONCLUSIONS In the present study , application of cloxacillin as antibiotic lock solution for dialysis catheters result ed in a considerable reduction in catheter-related bacteremia rate BACKGROUND AND OBJECTIVES Citrate 4 % has antithrombotic and antibacterial properties , which makes it a potentially superior alternative to heparin as an indwelling intraluminal locking agent . DESIGN , SETTING , PARTICIPANTS , AND MEASUREMENTS Sixty-one prevalent hemodialysis ( HD ) patients dialyzing with a tunneled cuffed HD catheter were r and omized in a pilot study to receive either heparin 5000 U/ml or citrate 4 % as a locking agent after HD . The primary outcomes were the development of catheter dysfunction ( defined as a blood pump speed < 250 ml/min or the use of tissue plasminogen activator ) and catheter-associated bacteremia . The secondary outcomes were the development of an exit-site infection or bleeding complications ( either local or systemic ) . RESULTS Citrate had comparable catheter dysfunction episodes to heparin ( 13/32 [ 41 % ] cases versus 12/29 [ 41 % ] cases , respectively ) . There were no differences in the development of catheter-associated bacteremia ( 2.2/1000 catheter days citrate versus 3.3/1000 catheter days heparin group ; P = 0.607 ) or exit-site infection ( 2.2/1000 catheter days for both groups ) . CONCLUSIONS The preliminary findings from our pilot study demonstrate that 4 % citrate is effective in maintaining catheter patency and does not appear to have any increased incidence of infections . Because citrate is significantly cheaper and has a more favorable side effect profile than heparin , it can be considered a potentially better locking agent in HD catheters Background Catheter-related bacteraemias ( CRBs ) contribute significantly to morbidity , mortality and health care costs in dialysis population s. Despite international guidelines recommending avoidance of catheters for haemodialysis access , hospital admissions for CRBs have doubled in the last decade . The primary aim of the study is to determine whether weekly instillation of 70 % ethanol prevents CRBs compared with st and ard heparin saline . Methods / design The study will follow a prospect i ve , open-label , r and omized controlled design . Inclusion criteria are adult patients with incident or prevalent tunneled intravenous dialysis catheters on three times weekly haemodialysis , with no current evidence of catheter infection and no personal , cultural or religious objection to ethanol use , who are on adequate contraception and are able to give informed consent . Patients will be r and omized 1:1 to receive 3 mL of intravenous- grade 70 % ethanol into each lumen of the catheter once a week and st and ard heparin locks for other dialysis days , or to receive heparin locks only . The primary outcome measure will be time to the first episode of CRB , which will be defined using st and ard objective criteria . Secondary outcomes will include adverse reactions , incidence of CRB caused by different pathogens , time to infection-related catheter removal , time to exit site infections and costs . Prospect i ve power calculations indicate that the study will have 80 % statistical power to detect a clinical ly significant increase in median infection-free survival from 200 days to 400 days if 56 patients are recruited into each arm . Discussion This investigator-initiated study has been design ed to provide evidence to help nephrologists reduce the incidence of CRBs in haemodialysis patients with tunnelled intravenous catheters . Trial Registration Australian New Zeal and Clinical Trials Registry Number : As a result of the high rate of infection , the NKF-K/DOQI guidelines recommended that an uncuffed catheter ( UC ) should not be used for longer than three weeks . However , the findings of the Dialysis Outcomes and Practice Patterns Study recognized that 48 % of new hemodialysis patients in the US and 75 % in Europe used UC for temporary access during arteriovenous fistula or graft maturation . The antibiotic lock technique ( ALT ) has been recommended to prevent catheter-related bacteremia ( CRB ) . Here , we prospect ively evaluated the efficacy of catheter-restricted filling using an antibiotic lock solution in preventing CRB . A total of 120 new hemodialysis patients requiring a temporary catheter while waiting for placement and maturation of an arteriovenous fistula or graft were enrolled in this study . Patients with a UC were r and omly assigned to receive either an antibiotic-heparin lock solution ( antibiotic group : cefazolin 10 mg/ml , gentamicin 5 mg/ml , heparin 1000 U/ml ) or a heparin lock solution ( no-antibiotic group : heparin 1000 U/ml ) as a catheter lock solution during the interdialytic period . The end point of the trial was CRB . CRB developed in seven ( 11.7 % ) patients in the no-antibiotic group ( Staphylococcus aureus , two ; Staphylococcus epidermidis , five ) whereas only one patient in the antibiotic group had S. aureus bacteremia . CRB rates per 1000 catheter-days were 0.44 in the antibiotic group versus 3.12 in the no-antibiotic group ( P=0.031 ) . Kaplan-Meier analysis also showed that mean CRB-free catheter survival of 59 days ( 95 % CI , 58 - 61 days ) in the antibiotic group was greater than that in the no-antibiotic group ( 55 days ; 95 % CI , 50 - 59 days ) . The results suggest that ALT may be a beneficial means of reducing the CRB rate in hemodialysis patients with UC Tunneled cuffed central vein catheters ( TCC ) are widely used for delivering hemodialysis ( HD ) . Infection is the principal cause of morbidity and mortality associated with central vein catheters in patients on HD . The optimal strategy to combat TCC infection is controversial . This prospect i ve study assesses the efficacy of antibiotic-lock therapy using vancomycin and gentamycin in preventing catheter-related blood stream bacterial infection in patients on HD . A total of 86 TCC in 69 HD patients were enrolled at the time of catheter insertion for delivering HD . Patients were r and omized into two groups : Group I ( 36 patients -39 insertions ) included TCC with antibiotic-lock therapy and Group II ( 33 patients -47 insertions ) with routine TCC management . Infection-free catheter survival of both groups was evaluated and compared at the end of the 18-month study period . A total of 72 TCC infections were detected with an incidence rate of 6.78 infections/1000 dialysis sessions . The rate of infection was significantly lower in Group I ( 4.39/1000 dialysis sessions ) compared to Group II ( 11.69/1000 dialysis sessions ) , p<0.001 . The bacteremia rate , as well as rate of clinical sepsis were also significantly lower in Group I than in Group II ( p<0.001 ) . There was no statistically significant difference in the rate of access site infection in the two groups ( p>0.05 ) . Our study suggests that antibiotic-lock therapy using a combination of vancomycin and gentamycin is useful in preventing catheter-related blood stream infection in patients on HD BACKGROUND Formation of an intraluminal microbial biofilm is noted to play a significant role in the development of catheter-related infections ( CRIs ) . Recently , it has been demonstrated that trisodium citrate ( TSC ) has superior antimicrobial effects over heparin for catheter locking . In this r and omized controlled trial , we compared the influence of catheter locking with heparin and TSC on the in vivo intraluminal biofilm formation in haemodialysis catheters . METHODS Six patients were studied from the time of catheter insertion for haemodialysis treatment . They were r and omly assigned to TSC 30 % or heparin 5000 U/ml for catheter locking for the duration of 1 month . After elective guidewire exchange of the catheter , the locking solution was also changed . After removal , catheters were dissected in three segments and examined by st and ardized scanning electron microscopy ( SEM ) to assess quantitative biofilm formation . Furthermore , st and ardized cultures of all segments were performed to identify any microorganisms . RESULTS In catheters filled with TSC , the average coverage by biofilm was 16 % versus 63 % in the heparin group ( P < 0.001 ) . A total of eight subsegments were associated with local catheter infection in the patients who were r and omized to heparin locking versus three subsegments who were assigned to TSC ( P < 0.05 ) . CONCLUSIONS Our study demonstrates that using TSC 30 % for catheter locking reduces the formation of microbial biofilm in haemodialysis catheters and culture-positive colonization . It is likely that this is the explanation for the observed prevention of CRIs by TSC locking Background and Purpose : Catheter-related bloodstream infection is the greatest threat to the safety of patients on hemodialysis . Catheter lock solutions containing heparin have been linked to an increased risk of hemorrhage and thrombocytopenia . Objectives : To ascertain the safety and efficacy for prevention of catheter-related bloodstream infection and catheter loss from patency failure of a novel catheter lock solution with antimicrobial and antithrombotic activity containing 0.24 M ( 7.0 % ) sodium citrate , 0.15 % methylene blue , 0.15 % methylparaben , and 0.015 % propylparaben ( C-MB-P ) , compared with heparin . Design : Multicenter , prospect i ve , r and omized , open-label trial with patients studied for up to 6 months . An independent clinical evaluation committee assessing trial outcomes was blinded to patients ' treatment assignments . Setting : Twenty-five outpatient hemodialysis units . Patients : Patients with end-stage renal disease receiving maintenance hemodialysis through a percutaneous cuffed and tunneled internal jugular hemodialysis catheters . Interventions : Participants ' catheters were locked between hemodialysis sessions with the C-MB-P lock solution or sterile saline containing 5000 units of unfractionated heparin ( control ) . Measurements and Main Results : We recorded and evaluated catheter-related bloodstream infections , catheter loss attributable to luminal thrombosis , and adverse events . A total of 407 patients participated in the trial ( 49,565 catheter days ) , 201 in the C-MB-P group and 206 in the heparin group . Patients in the two lock solution groups were comparable for risk factors predisposing to catheter-related bloodstream infection . Catheters locked with C-MB-P were significantly less likely to cause catheter-related bloodstream infection ( 0.24 vs. 0.82 per 1000 catheter days ; relative risk , 0.29 ; 95 % confidence interval , 0.12–0.70 ; p = .005 ) and were less likely to be lost because of patency failure ( 0 vs. 4 ; log rank , p = .04 ) . Conclusions : The novel C-MB-P lock solution is well tolerated , significantly reduces the risk of catheter-related bloodstream infection , and provides protection comparable to heparin against patency failure BACKGROUND The effectiveness of various solutions instilled into the central venous catheter lumens after each hemodialysis session ( catheter locking solutions ) to decrease the risk of catheter malfunction and bacteremia in patients undergoing hemodialysis is unknown . METHODS We r and omly assigned 225 patients undergoing long-term hemodialysis in whom a central venous catheter had been newly inserted to a catheter-locking regimen of heparin ( 5000 U per milliliter ) three times per week or recombinant tissue plasminogen activator ( rt-PA ) ( 1 mg in each lumen ) substituted for heparin at the midweek session ( with heparin used in the other two sessions ) . The primary outcome was catheter malfunction , and the secondary outcome was catheter-related bacteremia . The treatment period was 6 months ; treatment assignments were concealed from the patients , investigators , and trial personnel . RESULTS A catheter malfunction occurred in 40 of the 115 patients assigned to heparin only ( 34.8 % ) and 22 of the 110 patients assigned to rt-PA (20.0%)--an increase in the risk of catheter malfunction by a factor of almost 2 among patients treated with heparin only as compared with those treated with rt-PA once weekly ( hazard ratio , 1.91 ; 95 % confidence interval [ CI ] , 1.13 to 3.22 ; P = 0.02 ) . Catheter-related bacteremia occurred in 15 patients ( 13.0 % ) assigned to heparin only , as compared with 5 ( 4.5 % ) assigned to rt-PA ( corresponding to 1.37 and 0.40 episodes per 1000 patient-days in the heparin and rt-PA groups , respectively ; P = 0.02 ) . The risk of bacteremia from any cause was higher in the heparin group than in the rt-PA group by a factor of 3 ( hazard ratio , 3.30 ; 95 % CI , 1.18 to 9.22 ; P = 0.02 ) . The risk of adverse events , including bleeding , was similar in the two groups . CONCLUSIONS The use of rt-PA instead of heparin once weekly , as compared with the use of heparin three times a week , as a locking solution for central venous catheters significantly reduced the incidence of catheter malfunction and bacteremia . ( Current Controlled Trials number , IS RCT N35253449 . ) BACKGROUND Sodium citrate has antibacterial and anticoagulant properties that are confined to the catheter when used as a catheter lock . Studies of its use as a catheter lock have suggested its efficacy in preventing infection and bleeding complications compared with sodium heparin . STUDY DESIGN Open-label r and omized controlled trial of 2 catheter locks to examine the hypothesis that sodium citrate catheter locks will reduce catheter-related bacteremia and exit-site infection . SETTING S & PARTICIPANTS 232 consenting long-term hemodialysis patients in 4 satellite dialysis units to a large dialysis program with protocol ized treatment and targets . All patients were using twin-catheter single-lumen Tesio-Caths ( MedComp , Harleysville , PA ) . INTERVENTION 6 months ' use of 46.7 % sodium citrate ( citrate ) or 5 % heparin ( heparin ) locked postdialysis in the dead space of the central venous catheter . OUTCOMES & MEASUREMENTS Primary end point of catheter-related bacteremia and exit-site infection . Secondary end points of catheter thrombosis defined by the use of urokinase lock and infusion , new catheter insertion , catheter-related admission , blood transfusions , parenteral iron , and erythropoietin requirements . RESULTS Catheter-related bacteremia did not differ in the 2 groups , with an incidence of 0.7 events/1,000 catheter-days . There was no significant difference in rates of exit-site infection ( 0.7 versus 0.5 events/1,000 catheter-days ; P = 0.5 ) . The secondary end point of catheter thrombosis defined by the use of a urokinase lock was significantly more common in the citrate group , with an incidence of 8 versus 4.3/1,000 catheter-days ( P < 0.001 ) . Other secondary end points did not differ . Citrate treatment was curtailed compared with heparin because of a greater incidence of adverse events , with a mean treatment duration before withdrawal of 4.8 + /- 2.0 versus 5.7 + /- 1.2 months , respectively ( P < 0.001 ) . LIMITATIONS Low baseline catheter-related bacteremia and exit-site infection event rates may have underpowered this study . High adverse-event rates may have been related to high-concentration citrate that led to increased overspill and reduction in lock volume . This may also explain the increased rates of thrombosis in this group . CONCLUSION Widespread and long-term use of 46.7 % citrate catheter locks with Tesio-Cath access is not justified by this study Background Many patients with end-stage renal disease use a central venous catheter for hemodialysis access . A large majority of these catheters malfunction within one year of insertion , with up to two-thirds due to thrombosis . The optimal solution for locking the catheter between hemodialysis sessions , to decrease the risk of thrombosis and catheter malfunction , is unknown . The Prevention of Catheter Lumen Occlusion with rt-PA versus Heparin ( PreCLOT ) study will determine if use of weekly rt-PA , compared to regular heparin , as a catheter locking solution , will decrease the risk of catheter malfunction . Methods / Design The study population will consist of patients requiring chronic hemodialysis thrice weekly who are dialyzed with a newly inserted permanent dual-lumen central venous catheter . Patients r and omized to the treatment arm will receive rt-PA 1 mg per lumen once per week , with heparin 5,000 units per ml as a catheter locking solution for the remaining two sessions . Patients r and omized to the control arm will receive heparin 5,000 units per ml as a catheter locking solution after each dialysis session . The study treatment period will be six months , with 340 patients to be recruited from 14 sites across Canada . The primary outcome will be catheter malfunction , based on mean blood flow parameters while on hemodialysis , with a secondary outcome of catheter-related bacteremia . A cost-effectiveness analysis will be undertaken to assess the cost of maintaining a catheter using rt-PA as a locking solution , compared to the use of heparin . Discussion Results from this study will determine if use of weekly rt-PA , compared to heparin , will decrease catheter malfunction , as well as assess the cost-effectiveness of these locking solutions INTRODUCTION Catheter-related infection ( CRI ) is a major cause of morbidity and mortality in patients receiving hemodialysis . Antibiotic locking of these catheters has been shown to increase both the success of systemic antibiotic treatment in line sepsis , and to reduce the incidence of sepsis . We have studied the use of gentamicin locking of catheters ( in combination with st and ard heparin rather than previously reported citrate ) to reduce CRI rates . Furthermore , we have investigated the effects of this strategy on epoetin requirements and vascular access function . METHODS Fifty patients were studied . Patients were r and omized to catheter-restricted filling with either st and ard heparin ( 5000 IU/mL ) alone , or gentamicin and heparin ( 5 mg/mL ) . Epoetin requirements and hemoglobin response were monitored over the study period . RESULTS The gentamicin-locked group suffered only one infective episode ( 0.3/1000 catheter days ) compared to 10 episodes in six patients in the heparin alone group ( 4/1000 catheter days , P= 0.02 ) . The isolated organisms were equally split between Staphylococcal species and coliforms . There were no statistically significant differences in delivered dialysis dose ( Kt/V ) or QA between the two groups . Use of antibiotic locking was associated with both a higher mean hemoglobin ( 10.1 + /-0.14 g/dL vs. 9.2 + /- 0.17 g/dL in the heparin group , P= 0.003 ) and a lower mean epoetin dose ( 9000 + /- 734 IU/week vs. 10790 + /-615 IU/week in the heparin group , P= 0.04 ) . CONCLUSION The practice of locking newly inserted tunneled central venous catheters with gentamicin and heparin is an effective strategy to reduce line sepsis rates , and is associated with beneficial effects on epoetin requirements Background . A well-functioning vascular access ( VA ) is essential to efficient dialysis therapy . Guidelines have been implemented improving care , yet access use varies widely across countries and VA complications remain a problem . This study took advantage of the unique opportunity to utilize data from the Dialysis Outcomes and Practice Patterns Study ( DOPPS ) to examine international trends in VA use and trends in patient characteristics and practice s associated with VA use from 1996 to 2007 . DOPPS is a prospect i ve , observational study of haemodialysis ( HD ) practice s and patient outcomes at > 300 HD units from 12 countries and has collected data thus far from > 35 000 r and omly selected patients . Methods . VA data were collected for each patient at study entry ( 1996–2007 ) . Practice pattern data from the facility medical director , nurse manager and VA surgeon were also analysed . Results . Since 2005 , a native arteriovenous fistula ( AVF ) was used by 67–91 % of prevalent patients in Japan , Italy , Germany , France , Spain , the UK , Australia and New Zeal and , and 50–59 % in Belgium , Sweden and Canada . From 1996 to 2007 , AVF use rose from 24 % to 47 % in the USA but declined in Italy , Germany and Spain . Moreover , graft use fell by 50 % in the USA from 58 % use in 1996 to 28 % by 2007 . Across three phases of data collection , patients consistently were less likely to use an AVF versus other VA types if female , of older age , having greater body mass index , diabetes , peripheral vascular disease or recurrent cellulitis/gangrene . In addition , countries with a greater prevalence of diabetes in HD patients had a significantly lower percentage of patients using an AVF . Despite poorer outcomes for central vein catheters , catheter use rose 1.5- to 3-fold among prevalent patients in many countries from 1996 to 2007 , even among non-diabetic patients 18–70 years old . Furthermore , 58–73 % of patients new to end-stage renal disease ( ESRD ) used a catheter for the initiation of HD in five countries despite 60–79 % of patients having been seen by a nephrologist > 4 months prior to ESRD . Patients were significantly ( P < 0.05 ) less likely to start dialysis with a permanent VA if treated in a faciity that ( 1 ) had a longer time from referral to access surgery evaluation or from evaluation to access creation and ( 2 ) had longer time from access creation until first AVF cannulation . The median time from referral until access creation varied from 5–6 days in Italy , Japan and Germany to 40–43 days in the UK and Canada . Compared to patients using an AVF , patients with a catheter displayed significantly lower mean Kt/V levels . Conclusions . Most countries meet the contemporary National Kidney Foundation 's Kidney Disease Outcomes Quality Initiative goal for AVF use ; however , there is still a wide variation in VA preference . Delays between the creation and cannulation must be improved to enhance the chances of a future permanent VA . Native arteriovenous fistula is the VA of choice ensuring dialysis adequacy and better patient outcomes . Graft is , however , a better alternative than catheter for patients where the creation of an attempted AVF failed or could not be created for different reasons Infection of permanent catheters ( Permcath ) in hemodialysis ( HD ) patients can lead to catheter removal . The successful use of an antibiotic-lock to treat infection has reported good results in the treatment of catheters ' infections . This study was design ed to evaluate the impact of the intraluminal vancomycin in comparison with intravenous antibiotic administration . We included 67 ( 37 males and 30 females ) chronic HD patients requiring Permcath insertion at our tertiary care hospital from July 2004 to June 2007 . We studied two subgroups : an intervention group , which received 500 mg vancomycin infusion via both lumens of the Permcath and antibiotic lock of 1.5 mL each 48 hours with 1 g i.v . ceftriaxone every 12 hours for 7 days , followed by oral antibiotics according to the culture for three weeks ; and a control group , which received 500 mg intravenous vancomycin with daily 100 - 150 mg amikacin intravenously . Our endpoint was the rate of catheter removal . The patients characteristics including age , sex , time of insertion of the catheter and number of dialysis sessions per week did not differ between both subgroups . Of 28 patients in the intervention group , there was one catheter removal , and of 39 patients in the control group , there were 22 catheter removals , ( P < 0.001 ) . We conclude that administration of vancomycin as an antibiotic-lock in permcaths is more effective than its mere intravenous injection , and can increase the life span of catheters BACKGROUND An accepted pathogenesis of catheter-related bacteraemia ( CRB ) is the seeding of microorganisms from the intraluminal biofilm of central venous catheters . Antibiotic locks ( ABL ) are solutions containing high concentrations of antimicrobials with or without anticoagulants that aim to destroy the biofilm . METHODS In this study , two different ABL solutions , tissue plasminogen activator (TPA)-based and heparin-based ABL , used in conjunction with systemic antibiotics , were prospect ively compared in the treatment of CRB . RESULTS A total of 42 children on chronic haemodialysis with 11,016 catheter-days were observed for signs and symptoms of CRB over a period of 10 months . Twenty-four CRBs were diagnosed in 18 children ( 2.2 CRB/1000 catheter-days ) and were treated with the protocol . Symptoms of CRB resolved in 83 % within 48 h of treatment . None of the infected catheters required early emergent exchange or removal for poorly controlled CRB . Six children had recurrence of CRB within 6 weeks , of which four required catheter exchange . There was no specific microorganism or type of CRB that predisposed to higher recurrence rates . The mean infection-free survival of the catheters following TPA-ABL treatment was shorter than that following heparin-ABL treatment , but was not statistically significant by the log-rank test ( 126.8 + /- 81.6 days versus 154.5 + /- 70.4 days ) . CONCLUSION Both TPA-ABL and heparin-ABL used in conjunction with systemic antibiotics can effectively clear CRB without significant late recurrence at 6 weeks . Early use of ABL for management of CRB can potentially decrease the need for catheter removal , thus salvaging vascular access sites BACKGROUND Central venous catheters ( CVCs ) are used for vascular access in hemodialysis patients who have no alternative access or are awaiting placement or maturation of a permanent access . The major complications of CVCs are catheter-related bloodstream infection and clotting in the catheter lumen . STUDY DESIGN Parallel-group , r and omized , multicenter clinical trial , with patients blinded to study intervention . SETTING & PARTICIPANTS 16 free-st and ing dialysis facilities in Northern California belonging to a single provider . 303 adult maintenance hemodialysis patients who were using a tunneled cuffed CVC for vascular access . INTERVENTION The treatment group received an antibiotic lock containing gentamicin 320 μg/mL in 4 % sodium citrate , whereas the control group received the st and ard catheter lock containing heparin 1,000 U/mL. Both groups received triple-antibiotic ointment on the catheter exit site during dressing changes at each dialysis treatment . OUTCOMES Catheter-related bloodstream infection and catheter clotting . MEASUREMENTS Catheter-related bloodstream infection was defined as the occurrence of symptoms consistent with bacteremia together with positive blood culture results in the absence of another obvious source of infection . Catheter clotting was measured as the rate of thrombolytic agent use required to maintain adequate blood flow . A single patient could contribute more than one infection or clotting episode . RESULTS The rate of catheter-related bloodstream infection was 0.91 episodes/1,000 catheter-days in the control group and 0.28 episodes/1,000 catheter-days in the treatment group ( P = 0.003 ) . The time to the first episode of bacteremia was significantly delayed ( P = 0.005 ) . The rates of tissue plasminogen activator use were similar in the treatment and control groups : 2.36 versus 3.42 events/1,000 catheter-days , respectively ( P = 0.2 ) . LIMITATIONS The requirement for dialysis facility staff to prepare the treatment intervention prevented a completely blinded study . CONCLUSION Gentamicin 320 μg/mL in 4 % sodium citrate used as a routine catheter lock in CVCs in patients on maintenance hemodialysis therapy markedly decreases the incidence of catheter-related bloodstream infection and is as effective as heparin 1,000 U/mL in preventing catheter clotting Background We previously reported a reduction in central venous catheter ( CVC ) malfunction when using once-weekly recombinant tissue-plasminogen activator ( rt-PA ) as a locking solution , compared with thrice-weekly heparin . Objectives To identify risk factors for CVC malfunction to inform a targeted strategy for rt-PA use . Design Retrospective analysis . Setting Canadian hemodialysis ( HD ) units . Patients Adults with newly placed tunnelled upper venous system CVCs r and omized to a locking solution of rt-PA(1 mg/mL ) mid-week and heparin ( 5000 u/ml ) on the other HD sessions , or thrice-weekly heparin ( 5000 u/ml ) . Measurements CVC malfunction ( the primary outcome ) was defined as : peak blood flow less than 200 mL/min for thirty minutes during a HD session ; mean blood flow less than 250 mL/min for two consecutive HD sessions ; inability to initiate HD . Methods Cox regression was used to determine the association between patient demographics , HD session CVC-related variables and the outcome of CVC malfunction . Results Patient age ( 62.4 vs 65.4 yr ) , proportion female sex ( 35.6 vs 48.4 % ) , and proportion with first catheter ever ( 60.7 vs 61.3 % ) were similar between patients with and without CVC malfunction . After multivariate analysis , risk factors for CVC malfunction were mean blood processed < 65 L when compared with ≥ 85 L in the prior 6 HD sessions ( HR 4.36 ; 95 % CI , 1.59 to 11.95 ) , and mean blood flow < 300 mL/min , or 300 – 324 mL/min in the prior 6 HD sessions ( HR 7.65 ; 95 % CI , 2.78 to 21.01 , and HR 5.52 ; 95 % CI , 2.00 to 15.23 , respectively ) when compared to ≥ 350 mL/min . Limitations This pre-specified post-hoc analysis used a definition of CVC malfunction that included blood flow , which may result in an overestimate of the effect size . Generalizability of results to HD units where trisodium citrate locking solution is used may also be limited . Conclusions HD session characteristics including mean blood processed and mean blood flow were associated with CVC malfunction , while patient characteristics were not . Whether targeting these patients at greater risk of CVC malfunction with rt-PA as a locking solution improves CVC longevity remains to be determined . Abrégé Context eNous avons précédemment fait rapport d’une réduction du dysfonctionnement du cathéter veineux central ( CVC ) lors de l’utilisation hebdomadaire de l’activateur tissulaire du plasminogène obtenu par génie génétique ( rt-PA ) comme solution verrou , plutôt que l’administration d’héparine trihebdomadaire . ObjectifsDéterminer les facteurs de risques de dysfonctionnement du CVC afin d’indiquer une stratégie visée quant à l’utilisation du rt-PA.Type d’étudeAnalyse rétrospective . Context eLes services canadiens d’hémodialyse ( HD ) . Participants Adultes à qui on a nouvellement installé un CVC tunnellisé intravasculaire dans le système veineux supérieur , et qui ont reçu soit une solution verrou de rt-PA ( 1 mg/ml ) en milieu de semaine et de l’héparine ( 5 000 u/ml ) lors des autres séances d’HD , soit de l’héparine trois fois par semaine ( 5 000 u/ml).MesuresOn a défini le dysfonctionnement du CVC ( résultat primaire ) comme étant : un débit sanguin de pointe inférieur à 200 mL/min durant trente minutes , au cours d’une séance d’HD ; un débit sanguin moyen inférieur à 250 mL/min lors de deux séances d’HD consécutives ; l’impossibilité d’entamer l’HD.MéthodesOn a eu recours au modèle de régression de Cox pour déterminer l’association entre les données démographiques des participants , les variables relatives au CVC lors des séances d’HD et le résultat d’un dysfonctionnement du CVC.RésultatsL’âge des participants ( 62,4 c. 65,4 ans ) , la proportion des participants de sexe féminin ( 35,6 % c. 48,4 % ) , et la proportion de ceux à qui on a installé un cathéter pour la première fois ( 60,7 % c. 61,3 % ) étaient similaires entre les patients qui ont subi un dysfonctionnement du CVC et ceux qui n’en ont pas subi . L’analyse multifactorielle révèle que les facteurs de risque liés au dysfonctionnement du CVC sont un traitement moyen du sang < 65 L , comparativement à ≥ 85 L au cours des 6 séances d’HD précédentes ( HR 4,36 ; 95 % CI , 1,59 à 11,95 ) , et un débit sanguin moyen < 300 mL/min , ou 300 – 324 mL/min lors des 6 séances d’HD précédentes ( HR 7,65 ; 95 % CI , 2,78 à 21,01 , et HR 5,52 ; 95 % CI , 2,00 à 15,23 , respectivement ) , comparativement à ≥ 350 mL/min . Limites de l’étudeCette analyse prédéterminée et post-hoc reposait sur une définition du dysfonctionnement du CVC qui comprenait le débit sanguin , ce qui pourrait résulter en une surestimation de l’ampleur de l’effet réel . La validité externe des résultats pour les services d’HD qui utilisent le citrate trisodique comme solution verrou pourrait aussi être limitée . Conclusions Les caractéristiques des séances d’HD comprenant le traitement moyen du sang et le débit sanguin moyen ont été associées au dysfonctionnement du CVC , alors que les caractéristiques des participants ne l’ont pas été . Il reste à déterminer si le fait de cibler les patients courant un risque accru de dysfonctionnement du CVC avec rt-PA comme solution verrou améliore la longévité du CVC Purpose Sodium citrate has antibacterial and anticoagulant properties that are confined to the catheter when used as a catheter lock . Studies of its use as a catheter lock in chronic hemodialysis patients suggest it may be efficacious in preventing infection and thrombotic complications . We compared sodium citrate with saline catheter locks for non-tunneled hemodialysis central venous catheters in critically ill adult patients . Primary endpoint was catheter life span without complication . Methods This was a r and omized , controlled , open-label trial involving intensive care patients with acute renal failure requiring hemodialysis . Events were defined as catheter-related bloodstream infection and catheter malfunction . Results Seventy-eight patients were included . Median catheter life span without complication was 6 days ( saline group ) versus 12 days ( citrate group ) [ hazard ratio ( HR ) 2.12 ( 95 % CI 1.32–3.4 ) , p = 0.0019 ] . There was a significantly higher rate of catheter malfunction in the saline group compared with in the citrate group ( 127 catheter events/1,000 catheter-days , saline group vs. 26 events/1,000 catheter-days , citrate group , p < 0.00001 ) . There was no significant difference in incidence of infections between groups . We observed a significantly longer time to occurrence of infection in the citrate group ( 20 days vs. 14 days , HR 2.8 , 95 % CI 1.04–7.6 , p = 0.04 ) . By multivariate analysis , age and citrate group were the only independent factors that influenced catheter life span . Conclusions This study shows for the first time that citrate lock reduced catheter complications and increased catheter life span as compared to saline lock in critically ill adults requiring hemodialysis Background Tunnelled central venous dialysis catheter use is significantly limited by the occurrence of catheter-related infections . This r and omised controlled trial assessed the efficacy of a 48 hour 70 % ethanol lock vs heparin locks in prolonging the time to the first episode of catheter related blood stream infection ( CRBSI ) . Methods Patients undergoing haemodialysis ( HD ) via a tunnelled catheter were r and omised 1:1 to once per week ethanol locks ( with two heparin locks between other dialysis sessions ) vs thrice per week heparin locks . Results Observed catheter days in the heparin ( n=24 ) and ethanol ( n=25 ) groups were 1814 and 3614 respectively . CRBSI occurred at a rate of 0.85 vs. 0.28 per 1000 catheter days in the heparin vs ethanol group by intention to treat analysis ( incident rate ratio ( IRR ) for ethanol vs. heparin 0.17 ; 95%CI 0.02 - 1.63 ; p=0.12 ) . Flow issues requiring catheter removal occurred at a rate of 1.6 vs 1.4 per 1000 catheter days in the heparin and ethanol groups respectively ( IRR 0.85 ; 95 % CI 0.20 - 3.5 p = 0.82 ( for ethanol vs heparin ) . Conclusions Catheter survival and catheter-related blood stream infection were not significantly different but there was a trend towards a reduced rate of infection in the ethanol group . This study establishes proof of concept and will inform an adequately powered multicentre trial to definitively examine the efficacy and safety of ethanol locks as an alternative to current therapies used in the prevention of catheter-associated blood stream infections in patients dialysing with tunnelled catheters . Trial Registration Australian New Zeal and Clinical Trials Registry Purpose There is an increasing number of patients being dialyzed with permanent catheters ( PC ) . In the majority of cases , heparin is used to maintain PC patency . This practice causes clotting disturbances due to heparin leakage and may predispose the patient to bleeding episodes . It has not been well studied whether lowering heparin concentration for canal locking decreases short-term bleeding complications after PC placement . Methods This was a prospect i ve single-center r and omized open-label trial conducted in hemodialyzed patients undergoing PC insertion . Low concentration of heparin ( LCH ) 2,500 IU/ml versus high concentration of heparin ( HCH ) 5,000 IU/ml was r and omly used for catheter lumens locking . The primary endpoint was the occurrence of bleeding within 24 h after catheter placement . The effects of clinical and laboratory data on bleeding events were analyzed as secondary endpoints . Results Seventy-five patients ( 37 in LCH ) were enrolled in the study . Only in the HCH group we found a significant prolongation of activated partial thromboplastin time ( APTT ) 2 h after PC placement ( p < 0.001 ) . There was a higher number of bleeding episodes in the HCH group ( n = 16 ; 42.1 % ) than in the LCH group ( n = 7 ; 18.9 % ) ( χ2 = 4.74 ; p = 0.029 ) . In univariate analysis , assignment to HCH , baseline APTT , use of low molecular weight heparin , and femoral localization were associated with bleeding events . In multivariate analysis , the use of HCH ( odds ratio [ OR ] 3.64 ; 95 % confidence interval [ 95 % CI ] 1.10–12.05 ) and baseline APTT ( OR 1.12 ; 95 % CI 1.002–1.250 ) predicted bleeding after PC insertion . Conclusion LCH used for canals locking decreases bleeding events in the first 24 hours after permanent catheter placement , compared to HCH BACKGROUND Despite the US Dialysis Outcome Quality Initiative ) DOQI ( guidelines , for various reasons , increasing numbers of end-stage renal disease patients are becoming dependent on cuffed haemodialysis catheters ( HCs ) for chronic haemodialysis access . Their use is complicated by frequent failure due to thrombosis and catheter-related sepsis . In our unit , all HCs are put in place by the radiology department . METHODS In a prospect i ve study we looked at the outcome of all HCs over a three-year period , during which time 573 consecutive HCs were placed in 336 patients . Each line was followed individually until it was removed or until the end of the study . RESULTS In a survival analysis of those HCs removed following HC failure , HC half-life was 312 days and one-year HC survival was 47.5 % . The most frequent indications for HC removal were non-function ( 36.6 % ) , clinical suspicion of line sepsis ( 16.4 % ) and patient death ( 14.4 % ) . Using a Cox proportional hazards model , catheter number in a given patient and the presence of diabetes mellitus were found to be independent predictors of HC failure . The total incidence of HC-related sepsis was 1.3 episodes/1000 catheter days . The probability of developing bacteraemic HC-related sepsis was 27.5 % at one year . CONCLUSIONS Less than half of the HCs were removed electively because of availability of a more permanent mode of renal replacement , thereby illustrating the level of dependence that has developed on them as permanent access . Consequently , their limitations ( infection and malfunction ) are placing an ever increasing burden on the healthcare services Tunneled catheters are widely used for the provision of hemodialysis . Long-term catheter survival is limited by tunneled catheter-related infections ( CRI ) . This study assesses the efficacy of catheter-restricted filling with gentamicin and citrate in preventing CRI in hemodialysis patients . A double-blind r and omized study was conducted to compare heparin ( 5000 U/ml ) with gentamicin/citrate ( 40 mg/ml and 3.13 % citrate ; ratio 2:1 ) as catheter-lock solutions . A total of 112 tunneled catheters in 83 patients were enrolled at the time of catheter insertion for commencement or maintenance of hemodialysis . The primary end point was CRI . Catheter malfunction , defined as blood flow rate of < 200 ml/min for three consecutive dialyses and /or the use of urokinase , was also assessed as a secondary end point . Infection rates per 100 catheter-days were 0.03 in the gentamicin group versus 0.42 in the heparin group ( P = 0.003 ) . Kaplan-Meier survival analyses showed mean infection-free catheter survival of 282 d ( 95 % CI , 272 to 293 d ) in the gentamicin group versus 181 d ( 95 % CI , 124 to 237 d ) in the heparin group ( log rank , 9.58 ; P = 0.002 ) . Cox regression analyses showed a relative risk for infection-free catheter survival of 0.10 ( 95 % CI , 0.01 to 0.92 ) in the gentamicin group when adjusted for gender , race , diabetes mellitus , catheter malfunction , and hemoglobin ( P = 0.042 ) . The incidence of catheter malfunction was not significantly different between groups . Predialysis gentamicin levels were significantly higher in patients r and omized to gentamicin ( gentamicin/citrate : median 2.8 mg/L [ range , 0.6 to 3.5 mg/L ] , n = 5 ; heparin : median < 0.2 mg/L [ range < 0.2 to 0.2 mg/L ] , n = 5 ; P = 0.008 ) . Tunneled hemodialysis catheter-restricted filling with gentamicin and citrate is a highly effective strategy for prevention of CRI . Although citrate as a catheter-lock solution provides adequate anticoagulation for the interdialytic period , gentamicin levels suggest significant risk for chronic aminoglycoside exposure and associated ototoxicity . Before this technique is adopted , these preliminary observations warrant replication in future studies that will examine the efficacy and safety of lower doses of gentamicin or alternative agents with a reduced potential for toxicity BACKGROUND Hemodialysis catheter thrombosis is associated with loss of catheter patency , catheter-related bacteremia and sepsis . To limit these risks , many renal units use heparin as a catheter-locking solution . In this study we investigate the effect of different concentrations of heparin catheter lock solution on systemic anticoagulation in an investigator-blinded r and omized study of patients with non-tunneled ( temporary ) central venous catheters . METHODS 28 consecutive patients requiring insertion of a temporary non-tunneled dual lumen central venous hemodialysis catheter were r and omly allocated to receive either heparin 5,000 IU/ml or heparin 1,000 IU/ml as catheter lock solutions . The primary outcome measure was the difference in activated partial thromboplastin time ( APTT ) at 10 minutes following catheter locking with heparin 5,000 IU/ml and heparin 1,000 IU/ml . Secondary outcomes included intradialytic blood flow rates , catheter removal due to insufficient hemodialysis blood flow to maintain hemodialysis and catheter-related bacteremia . RESULTS 13 patients were r and omized to the heparin 1,000 IU/ml group with 15 patients r and omized to the heparin 5,000 IU/ml group . There was a statistically significant increase in APTT at 10 minutes between groups with median + 22.2 % ( range 0 - 210 ) rise in APTT in the heparin 1,000 IU/ml group compared with + 373.7 % ( range 133 - 800 ) in the heparin 5,000 IU/ml group ( p < 0.001 ) . There was no statistically significant difference between groups with the secondary outcomes of intradialytic blood flow , catheter failure rates and catheter-related bacteremia rates . CONCLUSIONS Heparin 1,000 IU/ml catheter lock solution confers a significantly lower risk of systemic heparinization than heparin 5,000 IU/ml without any overtly detrimental effect on intradialytic blood flow , catheter failure rates and catheter-related bacteremia rates A prospect i ve analysis was conducted comparing dysfunction attributable to catheter thrombosis in subjects who received a heparin catheter lock three times a week ( n = 15 ) to those who received a heparin lock six times a week ( n = 15 ) immediately after the insertion of a temporary haemodialysis catheter . Thrombus related catheter removal occurred in two patients in control but no patients in the experiment group . Heparin locking six times a week was found to be effective in prolonging the mean of the first day where difficulty was experienced in aspiration . It also prevented any possible difficulty in catheter flushing . Increased locking frequency prevents any thrombus accumulation within the temporary catheter , while it has limited but significant preventive effect on thrombus accumulated around the catheter Tunneled , cuffed central vein catheters ( TCC ) are widely used for delivering hemodialysis ( HD ) . Among the complications associated with central vein catheters in HD patients , infection is the principal cause of morbidity and mortality . The optimal strategy for management of TCC infections is unclear . This prospect i ve study was aim ed at assessing the efficacy of antibiotic-lock therapy using vancomycin and gentamycin in preventing catheter-related blood stream bacterial infection in patients on HD . A total of 63 HD patients with 81 TCC were enrolled at the time of catheter insertion . Patients were r and omized into two groups : Group I ( 33 patients , 37 insertions ) included TCC with antibiotic lock therapy and Group II ( 30 patients , 44 insertions ) with routine TCC management . Infection-free catheter survival of both groups was evaluated and compared at the end of the 12-month study period . A total of 57 TCC infections were encountered with an incidence rate of 8.95 infections per 1000 dialysis sessions ( DS ) . The rate of infection was significantly lower in Group I ( 4.54 per 1000 DS ) as compared to Group II ( 13.11 per 1000 DS ) , p 0.05 ) . Our study suggests that antibiotic-lock therapy using a combination of vancomycin and gentamycin is useful in preventing catheter-related blood stream infection in patients on HD BACKGROUND Bacteremia is a major cause of morbidity in patients using intravascular catheters . Interdialytic locking with antibiotics decreases the incidence of bacteremia , but risks antibiotic resistance . Taurolidine is a nontoxic broad-spectrum antimicrobial agent that has not been associated with resistance . Preliminary evidence suggests that taurolidine-citrate locks decrease bacteremia , but cause flow problems in established catheters . STUDY DESIGN Double-blind r and omized controlled trial . INTERVENTION Interdialytic locking with taurolidine and citrate ( 1.35 % taurolidine and 4 % citrate ) compared with heparin ( 5,000 U/mL ) started at catheter insertion . SETTING & PARTICIPANTS 110 adult hemodialysis patients with tunneled cuffed intravascular catheters inserted at 3 centers in Northwest Engl and . OUTCOMES & MEASUREMENTS Primary end points were time to first bacteremia episode from any cause and time to first use of thrombolytic therapy . RESULTS There were 11 bacteremic episodes in the taurolidine-citrate group and 23 in the heparin group ( 1.4 and 2.4 episodes/1,000 patient-days , respectively ; P = 0.1 ) . There was no significant benefit of taurolidine-citrate versus heparin for time to first bacteremia ( hazard ratio , 0.66 ; 95 % CI , 0.2 - 1.6 : P = 0.4 ) . Taurolidine-citrate was associated with fewer infections caused by Gram-negative organisms than heparin ( 0.2 vs 1.1 infections/1,000 patient-days ; P = 0.02 ) ; however , there was no difference for Gram-positive organisms ( 1.1 vs 1.2 infections/1,000 patient-days ; P = 0.8 ) . There was a greater need for thrombolytic therapy in the taurolidine-citrate versus heparin group ( hazard ratio , 2.5 ; 95 % CI , 1.3 - 5.2 ; P = 0.008 ) . LIMITATIONS Small sample size . The study included bacteremia from all causes and was not specific for catheter-related bacteremia . CONCLUSIONS Taurolidine-citrate use did not decrease all-cause bacteremia and was associated with a greater need for thrombolytic treatment . There was a decrease in infections caused by Gram-negative organisms and a trend to a lower frequency of bacteremia , which warrants further study BACKGROUND Tunneled-cuffed catheters ( TCC ) are often used among the elderly to commence and carry out haemodialysis ( HD ) . Complications like infection and thrombosis frequently reduce the lifespan of TCC . The role of an antibiotic heparin ' lock ' in the prevention of thrombotic and infectious complications and enhancement of TCC survival in the elderly has not been investigated previously . METHODS In this prospect i ve , double-blind clinical trial , TCC ( n = 119 , placed among 113 elderly patients requiring HD during March 2002 - February 2003 ) were r and omised to either group I having TCC ( n = 59 , placed in 58 elderly patients ) locked with cefotaxime ( 10 mg/mL ) and heparin ( 5000 U/mL ) , or group II with TCC ( n = 60 , placed in 55 elderly patients ) having catheter-restricted filling of heparin ( 5000 U/mL ) alone . Symptomatic catheter-related blood stream infections ( CRBSI ) and catheter thrombosis were the primary end points in this study . Thrombosis was defined as an inability to use the catheter at a blood flow of 200 mL/min that did not respond to catheter repositioning and /or intraluminal thrombolysis . The incidence of catheter thrombosis , CRBSI and percentage of catheter survival were estimated and statistically compared between the two groups . RESULTS Kaplan-Meier survival analysis using log rank test showed higher thrombosis-free TCC survival ( 84.7%vs 63.3 % , P = 0.021 ) , infection-free survival ( 68.7%vs 31.3 % , P < 0.001 ) and infection and thrombosis-free survival ( 65.0%vs 35.0 % , P = 0.006 ) at 365 days in group I compared with group II . CONCLUSION Cefotaxime and heparin locks safely and effectively enhance the lifespan of TCC by lowering the incidence of thrombotic and infectious complications among elderly end-stage renal failure ( ESRD ) patients Heparin and saline are commonly used to fill hemodialysis central venous catheters to prevent their thrombosis during the interdialytic period . The purpose of this prospect i ve clinical study was to evaluate whether replacing heparin with citrate or polygeline could ensure satisfactory catheter function without exposing patients to the risk of systemic heparinization . Thirty end-stage renal disease ( ESRD ) patients with subclavian or jugular single lumen catheters as temporary vascular access for hemodialysis were enrolled . After the insertion of the catheters , the patients were r and omly assigned to one of the following three filling groups : Group A , heparin ; Group B , citrate ; Group C , polygeline . Before each dialysis , the filling solution was aspirated and clot volume , if present , was measured . The catheter usage time and the clot volume were 23 + /- 24 days and 0.052 + /- 0.035 ml in Group A , 51 + /- 36 days and 0.059 + /- 0.032 ml in Group B , and 32 + /- 10 days and 0.056 + /- 0.038 ml in Group C , respectively . Our results indicate that citrate or polygeline can replace heparin effectively as a filling solution for single lumen temporary hemodialysis catheters There is growing concern about the development of antibacterial resistance with the use of antibiotics in catheter lock solutions . The use of an antibiotic that is not usually used to treat other serious infections may be an alternative that may reduce the clinical impact should resistance develop . We conducted a r and omized controlled trial to compare a solution of minocycline and EDTA with the conventional unfractionated heparin for the prevention of catheter-related bacteremia in hemodialysis patients during a period of 90 d. The study included 204 incident catheters ( 27.8 % tunneled ) ; 14 catheters were excluded because of early dysfunction and 3 because of protocol violations . We observed catheter-related bacteremia in 19 patients in the heparin group ( 4.3 per 1000 catheter-days ) and in 5 patients in the minocycline-EDTA group ( 1.1 per 1000 catheter-days ; P = 0.005 ) . We did not detect a significant difference in the rate of catheter removal for dysfunction . Catheter-related bacteremia-free survival was significantly higher in the minocycline-EDTA group than in the heparin group ( P = 0.005 ) . In conclusion , a minocycline-EDTA catheter lock solution is effective in the prevention of catheter-related bacteremia in hemodialysis patients BACKGROUND AND OBJECTIVE We previously demonstrated that minocycline-EDTA was efficacious at preventing catheter-related bloodstream infections ( BSIs ) in three patients with recurrent infections . This study compared heparin with minocycline-EDTA as flush solutions used among dialysis patients with central venous catheters , a high-risk group for catheter-related BSI . METHODS Patients were enrolled within 72 hours of catheter insertion and r and omized to receive heparin or minocycline-EDTA as a flush after each dialysis session . Each syringe containing flush solution was wrapped in orange plastic to conceal the type of solution it contained . Patients were observed for evidence of infection and catheter thrombosis . After catheters were removed , cultures were performed to determine whether microbial colonization had occurred . RESULTS During a 14-month period , 60 patients were enrolled ( 30 in each group ) . The two groups had similar demographics and underlying diseases . Catheter survival at 90 days was 83 % for the minocycline-EDTA group versus 66 % for the heparin group ( P = .07 ) . Significant catheter colonization , a surrogate measure of catheter-related infection , was significantly more frequent in the heparin group ( 9 of 14 vs 1 of 11 ; P = .005 ) . There was only one catheter-related bacteremia and it occurred in the heparin group . CONCLUSIONS When compared with heparin , minocycline-EDTA had a better 90-day catheter survival ( P = .07 ) and a decreased rate of catheter colonization . This pilot study warrants a larger prospect i ve , r and omized trial BACKGROUND The use of haemodialysis catheters is complicated by catheter-related sepsis . Intraluminal colonization of the catheter with bacteria is important in the pathogenesis of catheter-related sepsis . The use of a catheter lock solution containing the antimicrobial taurolidine might prevent bacterial colonization , thereby reducing the incidence of catheter-related sepsis . METHODS In a r and omized prospect i ve trial , patients receiving a dialysis catheter were included and catheters were locked with either heparin or a citrate-taurolidine-containing solution . Blood cultures drawn from the catheter lumen were routinely taken every 2 weeks and at time of removal of the catheter to detect bacterial colonization . Catheter-related sepsis and exit-site infections were registered for both groups . RESULTS A total of 76 catheters were inserted in 58 patients . The incidence of catheter colonization progressed slowly over time with no differences between dialysis catheters filled with heparin or citrate-taurolidine-containing solution . The number of exit-site infections was also similar between both groups . In the heparin group , four cases of catheter-related sepsis occurred as opposed to no sepsis episodes in the patients with catheters locked with the citrate-taurolidine-containing solution ( P<0.5 ) . No side effects with the use of citrate-taurolidine catheter lock solution were noted . CONCLUSIONS This study shows that catheter filling with a solution containing the antimicrobial taurolidine may significantly reduce the incidence of catheter-related sepsis . Taurolidine appears to be effective and safe and does not carry the risk for side effects that have been reported for other antimicrobial lock solutions containing gentamicin or high concentrations of citrate PURPOSE To determine the safety and efficacy of weekly prophylactic urokinase therapy in tunneled central venous access devices ( VADs ) . MATERIAL S AND METHODS A prospect i ve , r and omized study was performed in 105 patients who underwent tunneled VAD placement between March 1997 and April 1998 . The patients were r and omized to receive either twice-daily heparin flushes ( 14 heparin flushes per week ; group A , n = 52 ) or twice-daily heparin flushes with once-weekly urokinase ( UK ) instillation ( 13 heparin flushes , one UK flush per week ; group B , n = 53 ) . Patients were followed up by examination and /or interview at 1 , 3 , and 6 months for signs and symptoms of delayed catheter-related complications . RESULTS The total number of indwelling catheter-days was similar between groups ( 5,450 in group A , 5,276 in group B ) . The total number of infectious complications and fibrin sheaths formed was greater for group A ( n = 11 ; 21.1 % ) than group B ( n = 3 ; 5.7 % ) ( P = .02 ) . There were no side effects noted from the prophylactic UK administrations . CONCLUSION Prophylactic UK is advantageous in preventing delayed catheter-related complications The use of antibiotic lock solutions ( ALSs ) for the prevention of catheter-related blood stream infections ( CRBSIs ) is a promising option . The efficacy and safety of linezolid as ALS were evaluated in a r and omized double-blind prospect i ve study where 131 patients who required nontunneled catheter ( NTC ) for hemodialysis ( HD ) were r and omized to receive an ALS with either ( A ) unfractionated heparin ( 2000 U/ml ) alone as a catheter lock control , ( B ) vancomycin ( 5 mg/ml ) + heparin ( 2000 U/ml ) , or ( C ) linezolid ( 2 mg/ml ) + heparin ( 2000 U/ml ) . The primary endpoint of the study was CRBSI . A total of 152 NTCs were inserted in 131 patients . The linezolid-locked group did not present any infective episode ( CRBSI rate = 0/1000 catheter days ) compared with 2 episodes in the vancomycin-locked group ( CRBSI rate = 1.21/1000 catheter days , p = 0.1021 ) and 11 episodes in the heparin-locked group ( CRBSI rate = 6.7/1000 catheter days , p = 0.0001 ) . Median number of catheter days was greater in group C ( median = 38 ) compared with group B ( median = 36 , p = 0.0415 ) and with group A ( median = 34 , p = 0.0036 ) . No side effects and no resistant organisms were recorded with the use of linezolid ALS . Linezolid appears to be a safe and effective ALS , preventing CRBSI and prolonging the survival of the catheter in HD patients Tinzaparin offers some advantages over unfractionated heparin ( UFH ) for hemodialysis circuit anticoagulation . No study has compared these two molecules as hemodialysis catheter locks . This study aim ed to compare the efficacy of tinzaparin and UFH as locks for hemodialysis tunnelled central venous catheter in patients with end-stage renal disease ( ESRD ) . A r and omized , prospect i ve , single-blinded , controlled study was undertaken . Patients were r and omly assigned to receive UFH and tinzaparin for two 7-week periods in a crossover fashion . The doses used were 5,000 U of UFH and 2,000 U of tinzaparin per catheter line . The primary outcome was the need for thrombolytic catheter lock use defined with the Hemodialysis Unit alteplase protocol . Forty-two patients with ESRD were enrolled , totalling 815 UFH lock sessions and 729 tinzaparin lock sessions . A 47.4 % reduction in the incidence of alteplase lock use was observed with tinzaparin lock ( 3.16 % vs. 6.01 % , chi-square , p = 0.0078 ) . There was no significant difference in the time to first alteplase use between the two locks by Kaplan-Meier survival analysis ( logrank , p = 0.0900 ) . Our results suggest that tinzaparin could be an appropriate alternative for a hemodialysis tunnelled central venous catheter lock , but these results should be confirmed with a larger trial Background : Catheter-related infection ( CRI ) is associated with increased all-cause mortality and morbidity in hemodialysis patients and may be reduced by using antimicrobial lock solutions . But the safety of long-term use of antimicrobial lock still needs to be defined . Methods : Patients with a new inserted permanent tunneled cuffed hemodialysis catheter were r and omly assigned to an antibiotic lock solution of gentamicin ( 4 mg/ml ) heparin ( G group ) or heparin alone ( H group ) . Results : A total of 140 patients were enrolled in this study . CRI rates were 0.06/1,000 catheter-days for the G group versus 0.67 in the H group ( p = 0.014 ) . The risk of CRI was 10.54 higher in patients with a heparin-alone locked catheter ( p = 0.025 ) than that with gentamicin . The serum-measured gentamicin levels were very low . Conclusions : Gentamicin lock solution reduces CRI and improves catheter survival rates in hemodialysis patients . It is relatively safe in strictly catheter-restricted antibiotic lock solution therapy We prospect ively evaluated the efficacy and safety of a low concentrate citrate lock versus heparin lock in permanent single lumen hemodialysis catheters . The frequency of clot formation , complete catheter occlusion , flow problems and the use of urokinase as well as catheter infection episodes were monitored during 1370 dialysis sessions in 19 patients , r and omised in two study groups . There was a significantly higher number of dialysis sessions with clot formation in the citrate group but regarding the need for urokinase bolus or infusion , complete obstruction of the catheter or local infections , there were no statistically significant differences between groups . The higher incidence of clotting in the citrate locked catheters had no repercussion on dialysis efficiency , effective blood flow or on the use of thrombolytic therapy . We found that low concentrate citrate is as safe as heparin for long-term interdialytic anticoagulation of permanent single lumen hemodialysis catheters but is more efficient from a pharmaco-economic viewpoint Interdialytic hemodialysis catheter-locking solutions could contribute to a reduction of catheter-related complications , especially infections . However , they can cause side effects because of leakage from the tip of the catheter . Recently , trisodium citrate ( TSC ) has been advocated because of its antimicrobial properties and local anticoagulation . In a multicenter , double-blind , r and omized , controlled trial , TSC 30 % was compared with unfractionated heparin 5000 U/ml for prevention of catheter-related infections , thrombosis , and bleeding complications . The study was stopped prematurely because of a difference in catheter-related bacteremia ( CRB ; P < 0.01 ) . Of 363 eligible patients , 291 could be r and omized . The study included 98 tunneled cuffed catheters and 193 untunneled . There were no significant differences in patient and catheter characteristics on inclusion . In the heparin group , 46 % of catheters had to be removed because of any complication compared with 28 % in the TSC group ( P = 0.005 ) . CRB rates were 1.1 per 1000 catheter-days for TSC versus 4.1 in the heparin group ( P < 0.001 ) . For tunneled cuffed catheters , the risk reduction for CRB was 87 % ( P < 0.001 ) and for untunneled catheters was 64 % ( P = 0.05 ) . Fewer patients died from CRB in the TSC group ( 0 versus 5 ; P = 0.028 ) . There were no differences in catheter flow problems and thrombosis ( P = 0.75 ) . No serious adverse events were encountered . Major bleeding episodes were significantly lower in the TSC group ( P = 0.010 ) . TSC 30 % improves overall patency rates and reduces catheter-related infections and major bleeding episodes for both tunneled and untunneled hemodialysis catheters . Flow problems are not reduced Background : The objective of this study was to assess the impact of heparin concentration retained in temporary double-lumen catheters on bleeding risk . Methods : Activated partial thromboplastin time ( aPTT ) was measured in patients hemodialyzed via double-lumen catheters . Heparin solutions of 5,000 U/ml ( group 1 , n = 95 ) and 1,000 U/ml ( group 2 , n = 89 ) were r and omly retained in catheters after placement and each hemodialysis ( HD ) session . Blood transfusion , bleeding episodes , and changes of hematocrit were recorded . Results : The aPTT at the beginning of HD or 10 min after heparin lock was significantly prolonged , which was more prominent in the 5,000 U/ml group , whereas the aPTT declined to baseline values at the end of HD or before the next dialysis session in both groups . Infection and occlusion rates were similar in both groups . More patients suffered from major bleeding and prominent decline of hematocrit in the 5,000 U/ml group . Conclusions : Low-dose heparin ( 1,000 U/ml ) retention in double-lumen catheters for temporary HD maintains comparable catheter patency and might reduce the bleeding risk Staphylococcus aureus nasal carriers undergoing hemodialysis ( HD ) through tunneled cuffed catheters ( TCCs ) form a high-risk group for the development of catheter-related bloodstream infections ( CRBSI ) and ensuing morbidity . The efficacy of antibiotic-locks on the outcomes of TCCs among S. aureus nasal carriers has not been studied earlier . Persistent nasal carriage was defined by two or more positive cultures for methicillin-susceptible ( MSSA ) or methicillin-resistant ( MRSA ) S. aureus of five st and ardized nasal swabs taken from all the participants dialyzed at a large out-patient HD center affiliated to a tertiary care hospital . Of 218 participants , 82 S. aureus nasal carriers dialyzed through TCCs ( n = 88 ) were identified through April 2005 to March 2006 and r and omized to two groups . Group I comprised of 39 nasal carriers who had TCCs ( n = 41 ) " locked " with cefotaxime/heparin while group II included 43 patients with TCCs ( n = 47 ) filled with st and ard heparin . The CRBSI incidence and TCC survival at 365 days were statistically compared between the two groups . A significantly lower CRBSI incidence ( 1.47 vs. 3.44/1000 catheter-days , P < 0.001 ) and higher infection-free TCC survival rates at 365 days ( 80.5 vs. 40.4 % , P < 0.0001 ) were observed in the cefotaxime group compared with the st and ard heparin group . However , no significant difference in MRSA-associated CRBSI incidence was observed between the two groups . Cefotaxime-heparin " locks " effectively reduced CRBSI-incidence associated with gram-positive cocci , including MSSA , among S. aureus nasal carriers . There remains a compelling requirement for antibiotic-locks effective against MRSA Central venous catheters are used as permanent vascular access for chronic hemodialysis when construction of an arteriovenous fistula is not possible or contraindicated . We prospect ively evaluated the efficacy and safety of a 5 % citrate versus 10 % citrate catheter lock for permanent single-lumen dialysis catheters in a double-blind , crossover study of 28 patients during 1,876 dialysis sessions . There was a slightly higher number of dialysis sessions with clot formation in the 5 % citrate group ; entirely attributable to the formation of small clots . There was no statistically significant difference in the formation of large clots , complete obstruction of the catheter or the need for urokinase between the 2 study groups . In view of the ongoing debate on the safety of high-concentration citrate catheter locks , we conclude that a 5 % citrate lock is equally efficient in preventing catheter dysfunction compared with a 10 % citrate lock and is therefore the preferred citrate catheter-locking solution In a recent r and omized trial , weekly recombinant tissue plasminogen activator ( rt-PA ) , 1 mg per lumen , once per week , and twice-weekly heparin as a locking solution ( rt-PA/heparin ) result ed in lower risks of hemodialysis catheter malfunction and catheter-related bacteremia compared with thrice-weekly heparin ( heparin alone ) . We collected detailed costs within this trial to determine how choice of locking solution would affect overall health care costs , including the cost of locking solutions and all other relevant medical costs over the course of the 6-month trial . Nonparametric bootstrap estimates were used to derive 95 % confidence intervals ( CIs ) and mean cost differences between the treatment groups . The cost of the locking solution was higher in patients receiving rt-PA/heparin , but this was partially offset by lower costs for managing complications . Overall , the difference in unadjusted mean cost for managing patients with rt-PA/heparin versus heparin alone was Can$323 ( 95 % CI , -$935 to $ 1581 ; P=0.62 ) . When the costs were extrapolated over a 1-year time horizon using decision analysis , assuming ongoing rt-PA effectiveness , the overall costs of the strategies were similar . This finding was sensitive to plausible variation in the frequency and cost of managing patients with catheter-related bacteremia , and whether the benefit of rt-PA on catheter-related bacteremia was maintained in the long term . In summary , we noted no significant difference in the mean overall cost of an rt-PA/heparin strategy as a locking solution for catheters compared with thrice-weekly heparin . Cost savings due to a lower risk of hospitalization for catheter-related bacteremia partially offset the increased cost of rt-PA Abstract Background : Locking catheter with heparin may increase bleeding risk of some hemodialysis ( HD ) patients . Hence , the security and effectivity of 10 % concentrated sodium chloride ( CSC ) used as an alternative method for patients with high bleeding risk need to be investigated . Methods : Seventy-two patients inserted temporary central venous catheters were divided into two groups r and omly . A total of 3125 U/mL heparin saline ( HS ) was used in HS group and 10 % CSC in CSC group to lock catheters . Heparin-free HD was used for the first time and plasma specimens were collected to test coagulation indicators before catheter-locking ( at the end of HD ) and at 30 min after it . Then , blood flow velocities ( BFVs ) , incidences of catheter thrombosis , etc . were followed up at each time of HD . Results : Activated partial thromboplastin time ( APTT ) of two groups had no difference at the end of heparin-free HD ( 27.100 [ 25.675–28.950 ] vs. 27.250 [ 25.150–29.575 ] second , p = 0.933 ) , but at 30 minutes after using different catheter lock solutions , APTT of HS group was obviously longer than CSC group ( 50.100 [ 41.275–65.400 ] vs. 27.500 [ 25.525–29.875 ] second , p < 0.001 ) . Catheters ’ retaining time of two groups were the same ( p = 0.306 ) , so did the average BFVs ( p > 0.05 ) . But catheters ’ thrombosis incidence and urokinase usage of HS group were less than CSC group ( p < 0.05 ) . Conclusion : Comparing with HS group , thrombosis incidences of CSC group increased , but catheters ’ retaining time and average BFVs remained the same and coagulation indicators of it were unaffected . Therefore , it can be an effective alternative lock method for HD patients with high bleeding risk |
1,610 | 20,553,365 | Educational polymorphisms of BLS algorithms could build unpredictable barriers between rescuers and cardiac arrest victims and might seriously limit instructors ' educational effectiveness . | BACKGROUND A systematic review of the pooled effect of articles presenting current basic life support ( BLS ) algorithms for the treatment of cardiac arrest has never been carried .
AIMS We aim ed to record and classify potential inherent factors influencing simplicity negatively in teaching , learning and retention of cardiopulmonary resuscitation ( CPR ) delivered by health care providers or lay persons . | CONTEXT The survival benefit of well-performed cardiopulmonary resuscitation ( CPR ) is well-documented , but little objective data exist regarding actual CPR quality during cardiac arrest . Recent studies have challenged the notion that CPR is uniformly performed according to established international guidelines . OBJECTIVES To measure multiple parameters of in-hospital CPR quality and to determine compliance with published American Heart Association and international guidelines . DESIGN AND SETTING A prospect i ve observational study of 67 patients who experienced in-hospital cardiac arrest at the University of Chicago Hospitals , Chicago , Ill , between December 11 , 2002 , and April 5 , 2004 . Using a monitor/defibrillator with novel additional sensing capabilities , the parameters of CPR quality including chest compression rate , compression depth , ventilation rate , and the fraction of arrest time without chest compressions ( no-flow fraction ) were recorded . MAIN OUTCOME MEASURE Adherence to American Heart Association and international CPR guidelines . RESULTS Analysis of the first 5 minutes of each resuscitation by 30-second segments revealed that chest compression rates were less than 90/min in 28.1 % of segments . Compression depth was too shallow ( defined as < 38 mm ) for 37.4 % of compressions . Ventilation rates were high , with 60.9 % of segments containing a rate of more than 20/min . Additionally , the mean ( SD ) no-flow fraction was 0.24 ( 0.18 ) . A 10-second pause each minute of arrest would yield a no-flow fraction of 0.17 . A total of 27 patients ( 40.3 % ) achieved return of spontaneous circulation and 7 ( 10.4 % ) were discharged from the hospital . CONCLUSIONS In this study of in-hospital cardiac arrest , the quality of multiple parameters of CPR was inconsistent and often did not meet published guideline recommendations , even when performed by well-trained hospital staff . The importance of high- quality CPR suggests the need for rescuer feedback and monitoring of CPR quality during resuscitation efforts Objective : To compare cardiopulmonary resuscitation ( CPR ) with a compression to ventilation ( C : V ) ratio of 15:2 vs. 30:2 , with and without use of an impedance threshold device ( ITD ) . Design : Prospect i ve r and omized animal and manikin study . Setting : Animal laboratory and emergency medical technician training facilities . Subjects : Twenty female pigs and 20 Basic Life Support (BLS)-certified rescuers . Interventions , Measurements , and Main Results : Animals : Acid-base status , cerebral , and cardiovascular hemodynamics were evaluated in 18 pigs in cardiac arrest r and omized to a C : V ratio of 15:2 or 30:2 . After 6 mins of cardiac arrest and 6 mins of CPR , an ITD was added . Compared to 15:2 , 30:2 significantly increased diastolic blood pressure ( 20 ± 1 to 26 ± 1 ; p < .01 ) ; coronary perfusion pressure ( 18 ± 1 to 25 ± 2 ; p = .04 ) ; cerebral perfusion pressure ( 16 ± 3 to 18 ± 3 ; p = .07 ) ; common carotid blood flow ( 48 ± 5 to 82 ± 5 mL/min ; p < .001 ) ; end-tidal CO2 ( 7.7 ± 0.9 to 15.7 ± 2.4 ; p < .0001 ) ; and mixed venous oxygen saturation ( 26 ± 5 to 36 ± 5 , p < .05 ) . Hemodynamics improved further with the ITD . Oxygenation and arterial pH were similar . Only one of nine pigs had return of spontaneous circulation with 15:2 , vs. six of nine with 30:2 ( p < 0.03 ) . Humans : Fatigue and quality of CPR performance were evaluated in 20 BLS-certified rescuers r and omized to perform CPR for 5 mins at 15:2 or 30:2 on a recording CPR manikin . There were no significant differences in the quality of CPR performance or measurement of fatigue . Significantly more compressions per minute were delivered with 30:2 in both the animal and human studies . Conclusions : These data strongly support the contention that a ratio of 30:2 is superior to 15:2 during manual CPR and that the ITD further enhances circulation with both C : V ratios OBJECTIVE Multiple procedures performed in parallel may cause each procedure to be performed less effectively than if performed in isolation . BLS performed by prehospital providers potentially includes artificial ventilations , chest compressions , and application of an automated external defibrillator ( AED ) . This study examines the effectiveness of artificial ventilation and chest compressions both with and without an AED . METHODS Thirty-six prehospital providers participated in a prospect i ve observational study . Tested in pairs ( n=18 ) , subjects r and omly completed three , 6-min scenarios [ apneic patient with a pulse ( VENT ) , a pulseless patient ( CPR ) , and a pulseless patient with an AED available ( CPR+AED ) ] . A full-torso manikin capable of generating a carotid pulse was connected to a computer to record number of ventilations , tidal volume , flow rate , number of compressions , and compression depth . Data were analyzed by t-test , ANOVA , and Mann-Whitney U-test . RESULTS Artificial ventilation performed in isolation provided more correct ventilations than during CPR or CPR+AED ( 25.7 % , 14.2 % , 13.7 % , p=0.02 ) . Fewer ventilations were delivered during CPR and CPR+AED ( p=0.03 ) . More compressions were delivered with CPR alone vs. CPR+AED ( 51.9 , 35.7 min(-1 ) , p=0.00 ) . More correct compressions were delivered during CPR alone vs. CPR+AED ( p=0.05 ) . CONCLUSIONS Both the quality and quantity of BLS decreases as the number of procedures performed simultaneously increases . Further decrements might occur when ALS skills enter into resuscitation . These results suggest a need to automate and /or prompt the performance of BLS to optimize resuscitation Objectives : To discover the circumstances of out of hospital cardiac death irrespective of resuscitation attempts . Design : Prospect i ve community study over the two years 1994 and 1995 . Setting : The health districts of Brighton , South Glamorgan , and York , UK . Subjects : 1290 victims of sudden death or cardiac arrest caused by coronary heart disease who were under 76 years of age . Interventions : Basic and advanced life support for witnessed cardiac arrests . Main outcome measures : Survival to reach hospital and for 30 days after the arrest . Results : 35 ( 35 % ) of 101 patients ( mean age 64 ) whose arrest was witnessed by a doctor or paramedic survived for 30 days compared with 9 of 464 ( 2 % ) whose arrest was witnessed by a relative or byst and er at home ( mean age 66 ) and 15 of 200 ( 8 % ) whose arrest was witnessed in a public place ( mean age 61 ) . None of the 525 victims of an unwitnessed arrest survived but the majority of those whose arrest was witnessed had complained of new symptoms before the arrest . Victims who were given basic life support by relatives or byst and ers had better survival ( 14 of 183 ( 8 % ) ) than those who were not ( 10 of 481 ( 2 % ) , p < 0.001 ) . Of the 20 % of arrests that occurred in public places , few were in places where public access defibrillators would now be available . Conclusions : The burden of out of hospital cardiac arrest is mainly in the home but most victims have premonitory symptoms . Public education to seek help urgently for new or prolonged chest pain seems the most promising method to address the problem STUDY OBJECTIVE This study correlated the delay in initiation of byst and er cardiopulmonary resuscitation ( ByCPR ) , basic ( BLS ) or advanced cardiac ( ACLS ) life support , and transport time ( TT ) to survival from prehospital cardiac arrest . This was a secondary endpoint in a study primarily evaluating the effect of bicarbonate on survival . DESIGN Prospect i ve multicenter trial . SETTING Patients treated by urban , suburban , and rural emergency medical services ( EMS ) services . PATIENTS Eight hundred and seventy-four prehospital cardiac arrest patients . INTERVENTIONS This group underwent conventional ACLS intervention followed by empiric early administration of sodium bicarbonate noting resuscitation times . Survival was measured as the presence of vital signs on emergency department ( ED ) arrival . Data analysis utilized Student 's t-test and logistic regression ( p<0.05 ) . RESULTS Survival was improved with decreased time to BLS ( 5.52 min versus 6.81 min , p=0.047 ) and ACLS ( 7.29 min versus 9.49 min , p=0.002 ) intervention , as well as difference in time to return of spontaneous circulation ( ROSC ) . The upper limit time interval after which no patient survived was 30 min for ACLS time , and 90 min for transport time . There was no overall difference in survival except at longer arrest times when considering the primary study intervention bicarbonate administration . CONCLUSION Delay to the initiation of BLS and ACLS intervention influenced outcome from prehospital cardiac arrest negatively . There were no survivors after prolonged delay in initiation of ACLS of 30 min or greater or total resuscitation and transport time of 90 min . This result was not influenced by giving bicarbonate , the primary study intervention , except at longer arrest times OBJECTIVES To compare the quality of resuscitation between those with a simplified chest compression-only cardiopulmonary resuscitation ( CPR ) program and those with a conventional CPR program . METHODS The participants were r and omly assigned to either the 120-min training program of chest compressions ( chest compression-only CPR ) or the 180-min training program of chest compressions and ventilations ( conventional CPR ) . Main outcome measures were the net number of appropriate chest compressions during the 2-min test period and the proportion of appropriate chest compressions over the theoretically attainable number one month after the training . RESULTS 223 participants were enrolled and 104 in each group completed this study . The 2-min number of appropriate chest compressions was 86.1+/-57.2 in the chest compression-only CPR group , which was significantly greater than 57.1+/-30.2 in the conventional CPR group ( p<0.001 ) . The proportion of appropriate chest compressions was higher in the chest compression-only CPR group than in the conventional CPR group ( 47.1+/-31.1 % versus 38.1+/-20.1 % , p=0.022 ) . Time without chest compressions during conventional CPR reached 85.5+/-17.0 s out of 120 s , which was significantly longer than that during chest compression-only CPR ( 33.9+/-10.0 s , p<0.001 ) . The total number of ventilations and the number of appropriate ventilations during 2 min was 2.5+/-3.0 and 0.9+/-1.6 , respectively . CONCLUSIONS A simplified chest compression-only CPR program makes it possible for the general public to perform a greater number of appropriate chest compressions than the conventional CPR program ( UMIN-CTR C0000000321 ) BACKGROUND Despite a large amount of data assessing outcomes of out-of-hospital cardiac arrests ( OHCAs ) , little information is available about physician-staffed emergency medical service ( EMS ) systems . The aim of our study was to investigate the impact of a physician on the outcome of patients after OHCA . METHODS This is a prospect i ve , observational study that included 539 consecutive patients ( 63.9 + /- 19.1 years old ; 349 males ) with OHCA in the community of Dachau ( 135,000 inhabitants ) in whom resuscitation was attempted between January 2000 and January 2006 according to Utstein style . Patients were followed up to hospital discharge . The primary end point of the study was that the patients was discharged alive from hospital . RESULTS Of 412 patients with an OHCA , 180 ( 43.7 % ) were admitted to hospital , and 47 ( 11.4 % ) were discharged alive . Resuscitation was started by a physician in 117 ( 28.4 % ) patients , by a layperson in 118 ( 28.6 % ) , or by an EMS personnel in 177 ( 43.0 % ) . A total of 18 patients ( 18.6 % ) treated by physicians , 13 patients ( 8.0 % ) treated by EMS personnel ( P = .02 vs treatment by physician ) , and 16 patients ( 16.5 % ) resuscitated by laypersons were discharged from hospital ( P = .8 vs treatment by physician ) . In 105 patients with byst and er-witnessed OHCA of cardiac origin with shockable rhythm , the discharge rate was 32.4 % ( n = 34 ) . Multivariate analysis identified ventricular fibrillation on first electrocardiogram , observed OHCA , short response time intervals but not the unit that performed the first resuscitation attempt as independent predictors of survival . CONCLUSIONS A physician on board of the advanced life support unit was not identified as an independent factor of improved survival Context Emergency medical services ( EMS ) personnel attending out-of-hospital cardiac arrests sometimes attempt to resuscitate patients who do not want life-sustaining measures . Contribution This study involving 2770 patients with EMS-attended cardiac arrests assessed outcomes of guidelines that permitted personnel to withhold resuscitation in patients with terminal illnesses when the patients or caregivers indicated , in writing or verbally , that they did not want resuscitation . Sixteen of 35 EMS agencies in King County , Washington , implemented the guidelines . Implementation and control agencies withheld resuscitation in approximately 11.8 % and 5.3 % of cardiac arrests , respectively . The difference was primarily due to honoring verbal requests . Caution s In this observational study , self-selected agencies volunteered to implement guidelines . The Editors Emergency medical services ( EMS ) personnel arrive at a home to find an elderly , emaciated patient in cardiac arrest . Family members state that he had end-stage cancer and did not want life-sustaining measures to be taken . However , there is no formal written do-not-resuscitate ( DNR ) order . The emergency medical technicians ( EMTs ) remove the patient from bed , despite the now vehement and emotional objections of the family , and begin resuscitation . This scenario , based on an actual event , shows a predicament sometimes faced by EMS personnel who arrive on the scene and find a patient with a terminal condition who has previously expressed the wish that no resuscitation be attempted . The response of EMS personnel to such patients is often inconsistent and depends on local guidelines , patient presentation , and type of DNR order . As of 1999 , 42 states had adopted formal protocol s that allowed EMS personnel to withhold resuscitation efforts if the patient had a specific , state-approved prehospital DNR order ( 1 ) . However , when this is lacking and when resuscitation wishes are conveyed by a different type of directive or by verbal request , EMS personnel usually begin resuscitation . An unwanted resuscitation effort may violate the patient 's right to self-determination , cause suffering and emotional distress for the patient and the family , be troubling for EMS providers , and expend re sources unnecessarily . Discussion s with providers in our EMS system and our personal experiences underscored the importance of this issue and prompted us to develop new guidelines that gave EMS personnel greater discretion to withhold resuscitation efforts in patients with terminal conditions , even in the absence of state-approved prehospital DNR documentation . The guidelines were implemented by some , but not all , EMS agencies in our county . We hypothesized a priori that EMS personnel from agencies implementing the guidelines would probably withhold resuscitation more often than those from agencies not implementing the guidelines , specifically because the guidelines allowed EMS personnel to honor verbal requests . We also hypothesized that EMS personnel would make decisions consistent with the guidelines and that they would report little difficulty in making these decisions . Methods Study Design , Setting , and Sample This investigation was an observational study of persons having out-of-hospital cardiac arrests in King County , Washington ( excluding Seattle ) , and incorporated historical and contemporary comparison groups ( Figure ) . King County , excluding Seattle , comprises urban , suburban , and rural areas ; has a population of approximately 1.2 million persons ; and covers 2043 square miles . King County has a 2-tiered EMS response system that has been described previously ( 2 ) . First-tier firefighter-EMTs are first to arrive on the scene and provide cardiopulmonary resuscitation and defibrillation ; second-tier paramedics arrive next and provide advanced life support . Figure . Study design . The study sample consisted of all cases of out-of-hospital cardiac arrest to which EMS personnel responded , except those for which DNR orders would not typically be pertinent ( trauma , suicide , or drug overdose ) . Although the term cardiac arrest is used by EMS personnel to denote persons who are unconscious and do not have a pulse , there may be cardiac , respiratory , neurologic , or other causes for the patient 's condition . The institutional review board at the University of Washington approved the study . Written informed consent was not required . Verbal consent was obtained from EMS personnel before they were interviewed . Intervention Before 1998 , patient care guidelines directed EMS personnel in King County to initiate resuscitation attempts in all persons having cardiac arrest , except those with signs of obvious death ( lividity or rigor mortis ) or those with a state-approved prehospital DNR directive . Other written directives were occasionally honored , although this was not endorsed . Verbal requests were rarely honored . In 1998 , 2 of the present authors , who work as paramedics in King County , proposed new guidelines to address the situation of patients with terminal conditions who did not desire resuscitation and did not have DNR paperwork . These guidelines allowed EMS providers to withhold resuscitation if 1 ) the patient had a preexisting terminal condition and 2 ) the patient , family , or caregivers indicated , in writing or verbally , that the patient did not want resuscitation . A terminal condition was defined as one in which death was expected and for which the patient was under a physician 's care . Resuscitation wishes could be communicated through a state-approved prehospital DNR directive , other directive , or verbal request . Although the guidelines were valid for both EMTs and paramedics , we expected that they would be most useful to EMTs , who are first to arrive at the scene . Physician consultation was not necessary to invoke the guidelines . Assistance in developing the guidelines and training program was provided by the King County medical director , local physicians , paramedics , EMS administrators , and a legal consultant ( Johnson BR . Liability of EMS personnel for honoring or failing to honor a Do Not Resuscitate ( DNR ) order . Legal opinion paper presented to King County Emergency Medical Services . May 1998 ) . The guidelines and training were offered to all 35 EMS agencies in King County . Participation was voluntary , and each agency 's fire chief made the final decision . Ultimately , 16 agencies chose to participate . Those that did not participate cited legal and risk management concerns . Characteristics of participating and nonparticipating agencies and the population s they serve are shown in Table 1 . The 35 agencies have the same countywide medical director , continuing education program , patient care guidelines , and criteria -based dispatch guidelines . Table 1 . Characteristics of Participating and Nonparticipating Agencies Personnel from participating agencies were trained in 1998 . Training consisted of a printed manual , written guidelines , a 2-hour lecture and discussion , and a competency quiz . Approximately 900 EMTs and 70 paramedics were trained . Because some agencies participated and some did not , we were able to compare EMS care between these groups . We compared resuscitation decisions for 1-year periods before and after the introduction of the guidelines : pre guideline ( calendar year 1997 , the last full year before guideline implementation ) and post guideline ( calendar year 1999 , the first full year after guideline implementation ) . Cases occurring in 1998 were excluded because training took place that year . This classification generated 4 groups : pre guideline nonparticipating agencies , pre guideline participating agencies , post guideline nonparticipating agencies , and post guideline participating agencies . Within these groups , each case of cardiac arrest was classified into 1 of 3 categories : attempted resuscitation , no resuscitation due to signs of irreversible death , or withheld resuscitation . Withheld resuscitation consisted of cases where resuscitation was withheld on the basis of either a written DNR order or verbal request . Data Collection For each EMS response , information was collected from the medical incident report that was completed by EMTs and paramedics . After implementation of the guidelines , 1 of the authors conducted interviews to collect information on cases of withheld resuscitation . Each interview lasted approximately 15 minutes and included 30 questions about the patient , scene , family members , and actions of EMS personnel . The EMS personnel obtained most information from family members ( for example , the patient 's history and diagnosis and the reason for the 911 telephone call ) , although no st and ard query was used . When possible , the interview took place within 1 day of the telephone call , but there were occasional delays of 1 week or more . Interviews were conducted for 51 of 99 cases of withheld resuscitation . The EMS officer in charge of patient care for each case was interviewed . No persons declined to be interviewed . Statistical Analysis Descriptive statistics summarize the characteristics of the patient sample . A multinomial logistic regression model was used to estimate probabilities for the 3 nominal response categories of attempted resuscitation , no resuscitation , and withheld resuscitation . Independent variables included factors of time ( pre guideline or post guideline implementation ) , participating agency ( yes or no ) , patient location ( private residence , nursing home , or other ) , patient sex ( male or female ) , a covariate of patient age in years divided by 100 , and an interaction term of time and participating agency . Individual agency identification was not tabulated for each observation or medical incident report ; therefore , a r and om-effects term for agency was not entered into the model . A multiple imputation method using the expectation-maximization algorithm for continuous and categorical data was used for missing data in 89 cases of age and 46 cases of sex . Chi-square tests AIM OF THE STUDY External chest compression ( ECC ) is an essential part of cardiopulmonary resuscitation and usually performed without any adjuncts . Although different supportive devices have been developed , none have yet been implemented as a st and ard procedure to guide rescuers in resuscitation . This study investigates the effects of the CPREzy-pad on ECC performed by first year medical students during simulated cardiac arrest . MATERIAL S AND METHODS Two hundred and two subjects were r and omised and asked to perform 5 min of single-rescuer-CPR . Group 1 ( n = 111 ) was taught classic ECC , followed by ECC with the CPREzy and was tested in ECC with the CPREzy . Group 2 ( n = 91 ) was taught and tested in classic ECC only . One week later each group was divided : Group 1A was tested in ECC with the CPREzy again ; Group 1B was tested in classic ECC . Group 2A was taught and tested in ECC with CPREzy ; Group 2B was tested in classic ECC again . Primary endpoints were compression rate ( 90 - 110/min ) and compression depth ( 40 - 50 mm ) . RESULTS Comparing groups 1 and 2 , ECC was significantly superior with CPREzy ( correct rate : 93.7 % versus 19.8 % , p < or = 0.01 ; depth : 71.2 % versus 34.1 % , p < or = 0.01 ) . The group tested with CPREzy initially 1 week later ( 2A ; n = 36 ) improved significantly in correct compression rate ( 19.8 % versus 88.9 % , p < or = 0.01 ) and compression depth ( 34.1 % versus 75.0 % , p < or = 0.02 ) . The control-group ( 2B ; n = 55 ) without CPREzy demonstrated poor performance in both evaluations ( correct rate : 19.8 % versus 25.5 % , depth : 34.1 % versus 43.6 % ) . CONCLUSION CPREzy as a simple portable and re-usable device is able to improve performance of ECC in simulated cardiac arrest STUDY HYPOTHESIS Tracheal intubation should improve the quality of cardiopulmonary resuscitation ( CPR ) by enabling adequate ventilation without pauses in external chest compressions . METHODS Out-of-hospital cardiac arrests of all causes were sample d in this non-r and omized , observational study of advanced cardiac life support in three ambulance services ( Akershus , London and Stockholm ) . Prototype defibrillators ( Heartstart 4000SP , Philips Medical Systems , And over , MA , USA and Laerdal Medical AS , Stavanger , Norway ) registered all chest compressions via an extra chest pad with an accelerometer mounted over the lower part of sternum and ventilations from changes in transthoracic impedance between the st and ard defibrillator pads . The quality of CPR was analyzed off-line for 119 episodes . Numbers and differences are given as mean + /- S.D. and differences as mean and 95 % confidence intervals . RESULTS Chest compressions were not given in cardiac arrest for 61 + /- 20 % of the time before intubation compared to 41 + /- 18 % after intubation ( difference : 20 % ( 16 - 24 % ) ) . Compressions and ventilations per minute increased from 47 + /- 25 to 71 + /- 23 ( difference : 24 ( 19 , 29 ) ) and 5.6 + /- 3.7 to 14 + /- 5.0 ( difference : 8.7 ( 7.6 , 9.8 ) ) respectively . Four cases of unrecognized oesophageal intubation ( 3 % ) were suspected from the disappearance of ventilation induced changes in thoracic impedance after intubation . CONCLUSION The quality of CPR improved after tracheal intubation , but the fraction of time without blood flow was still high and not according to international guidelines . On-line analysis of thoracic impedance might be a practicable aid to avoid unrecognized oesophageal intubation , but this area needs further research Cardiopulmonary resuscitation ( CPR ) provides possible survival from otherwise fatal cardiopulmonary collapse . Termination guidelines have been developed for use when resuscitation has no potential benefit for a victim . The purpose of this prospect i ve cohort study was to determine if unwitnessed collapse combined with no-byst and er cardiopulmonary resuscitation would support a decision to terminate attempted resuscitation . There were 541 patients analyzed during 6 months , with functional neurological survival the outcome of interest . There were no functional neurological survivors at hospital discharge among the 180 victims in the unwitnessed , no-byst and er CPR subgroup ( 95 % confidence interval [ CI ] 0.0%-2.1 % ) . Functional neurological survival for witnessed collapse , byst and er CPR was 6.0 % ( 95 % CI 2.8%-12.5 % ) , for witnessed collapse , no-byst and er CPR was 3.8 % ( 95 % CI 1.9%-7.7 % ) , and for unwitnessed collapse , byst and er CPR 1.3 % ( 95 % CI 0.2%-6.9 % ) . With confirmation by further studies , unwitnessed collapse and lack of byst and er CPR may be a practical addition to resuscitation termination guidelines |
1,611 | 27,819,886 | The trials evaluating bisphosphonates reported greater reduction in foot temperature and disease activity for intervention subjects compared with controls .
Another outcome of this review indicated additional beneficial effects of bisphosphonates in reducing pain and discomfort .
Bisphosphonates may be useful adjuncts to st and ard management of Charcot foot by improved healing demonstrated by a reduction in disease activity indicated by skin temperature and bone destruction .
Magnetic therapy may reduce deformity , joint destruction and improve mobility .
CONCLUSION There is a lack of evidence supporting the use of pharmacological or non-surgical interventions with reducing lesions , ulceration , rate of surgical intervention , hospital admissions and improving the quality of life of subjects with Charcot foot .
Bisphosphonates may improve the healing of Charcot foot by reducing skin temperature and disease activity of Charcot foot , when applied in addition to st and ard interventions to control the position and shape of the foot | BACKGROUND Charcot neuropathic osteoarthropathy is commonly known as ' Charcot foot ' .
It is a serious foot complication of diabetes mellitus that can frequently lead to foot ulceration , gangrene , hospital admission and foot amputation .
A multidisciplinary approach to the management of Charcot foot is taken involving medical and allied health professionals .
The management approach may also differ between different countries .
To date , there is no systematic review of the literature undertaken to identify the clinical effectiveness of non-operative interventions in the treatment of acute Charcot foot .
OBJECTIVE The objective of this review was to identify the effectiveness of non-surgical interventions with reducing lesions , ulceration , the rate of surgical intervention , reducing hospital admissions and improve the quality of life of subjects with Charcot foot . | OBJECTIVE Little prospect i ve research exists on risk factors for diabetic foot ulcer that considers the independent effects of multiple potential etiologic agents . We prospect ively studied the effects of diabetes characteristics , foot deformity , behavioral factors , and neurovascular function on foot ulcer risk among 749 diabetic veterans with 1,483 lower limbs . RESEARCH DESIGN AND METHODS Eligible subjects included all diabetic enrollees of a general internal medicine clinic without foot ulcer , of whom 83 % agreed to participate . Baseline assessment included history and lower-limb physical examination , tests for sensory and autonomic neuropathy , and measurements of macro- and microvascular perfusion in the foot . Subjects were followed for the occurrence of a full thickness skin defect on the foot that took > 14 days to heal , with a mean follow-up of 3.7 years . RESULTS Using stepwise Cox regression analysis , the following factors were independently related to foot ulcer risk : foot insensitivity to the 5.07 monofilament ( relative risk [ 95 % CI ] ) 2.2 ( 1.5 - 3.1 ) , past history of amputation 2.8 ( 1.8 - 4.3 ) or foot ulcer 1.6 ( 1.2 - 2.3 ) , insulin use 1.6 ( 1.1 - 2.2 ) , Charcot deformity 3.5 ( 1.2 - 9.9 ) , 15 mmHg higher dorsal foot transcutaneous PO2 0.8 ( 0.7 - 0.9 ) , 20 kg higher body weight 1.2 ( 1.1 - 1.4 ) , 0.3 higher ankle-arm index 0.8 ( 0.7 - 1.0 ) , poor vision 1.9 ( 1.4 - 2.6 ) , and 13 mmHg orthostatic blood pressure fall 1.2 ( 1.1 - 1.5 ) . Higher ulcer risk was associated with hammer/claw toe deformity and history of laser photocoagulation in certain subgroups . Unrelated to foot ulcer risk in multivariate models were diabetes duration and type , race , smoking status , diabetes education , joint mobility , hallux blood pressure , and other foot deformities . CONCLUSIONS Certain foot deformities , reduced skin oxygenation and foot perfusion , poor vision , greater body mass , and both sensory and autonomic neuropathy independently influence foot ulcer risk , thereby providing support for a multifactorial etiology for diabetic foot ulceration OBJECTIVE The purpose of this study was to compare the effectiveness of a removable cast walker ( RCW ) rendered irremovable ( iTCC ) with the total contact cast ( TCC ) in the treatment of diabetic neuropathic plantar foot ulcers . RESEARCH DESIGN AND METHODS In a prospect i ve , r and omized , controlled trial , 41 consecutive diabetic patients with chronic , nonischemic , neuropathic plantar foot ulcers were r and omly assigned to one of two groups : a RCW rendered irremovable by wrapping it with a single layer of fiberglass casting material ( i.e. , an iTCC ) or a st and ard TCC . Primary outcome measures were the proportion of patients with ulcers that healed at < /=12 weeks , healing rates , complication rates , cast placement/removal times , and costs . RESULTS The proportions of patients with ulcers that healed within 12 weeks in the iTCC and TCC groups were 80 and 74 % , respectively ( 94 and 93 % , respectively , when patients who were lost to follow-up were excluded ) . Survival analysis ( healing rates ) was statistically equivalent in the two groups , as were complication rates , but with a trend toward benefit in the iTCC group . The iTCC took significantly less time to place and remove than the TCC with 39 % and 36 % reductions , respectively . There was also an overall lower cost associated with the use of the iTCC compared with the TCC . CONCLUSIONS The iTCC may be equally efficacious , faster to place , easier to use , and less expensive than the TCC in the treatment of diabetic plantar neuropathic foot ulcers OBJECTIVE To evaluate the effectiveness of at-home infrared temperature monitoring as a preventative tool in individuals at high risk for diabetes-related lower-extremity ulceration and amputation . RESEARCH DESIGN AND METHODS Eighty-five patients who fit diabetic foot risk category 2 or 3 ( neuropathy and foot deformity or previous history of ulceration or partial foot amputation ) were r and omized into a st and ard therapy group ( n = 41 ) or an enhanced therapy group ( n = 44 ) . St and ard therapy consisted of therapeutic footwear , diabetic foot education , and regular foot evaluation by a podiatrist . Enhanced therapy included the addition of a h and held infrared skin thermometer to measure temperatures on the sole of the foot in the morning and evening . Elevated temperatures ( > 4 degrees F compared with the opposite foot ) were considered to be " at risk " of ulceration due to inflammation at the site of measurement . When foot temperatures were elevated , subjects were instructed to reduce their activity and contact the study nurse . Study subjects were followed for 6 months . RESULTS The enhanced therapy group had significantly fewer diabetic foot complications ( enhanced therapy group 2 % vs. st and ard therapy group 20 % , P = 0.01 , odds ratio 10.3 , 95 % CI 1.2 - 85.3 ) . There were seven ulcers and two Charcot fractures among st and ard therapy patients and one ulcer in the enhanced therapy group . CONCLUSIONS These results suggest that at-home patient self-monitoring with daily foot temperatures may be an effective adjunctive tool to prevent foot complications in individuals at high risk for lower-extremity ulceration and amputation BACKGROUND Limited ankle dorsiflexion has been implicated as a contributing factor to plantar ulceration of the forefoot in diabetes mellitus . The purpose of this study was to compare outcomes for patients with diabetes mellitus and a neuropathic plantar ulcer treated with a total-contact cast with and without an Achilles tendon lengthening . Our primary hypothesis was that the Achilles tendon lengthening would lead to a lower rate of ulcer recurrence . METHODS Sixty-four subjects were r and omized into two treatment groups , immobilization in a total-contact cast alone or combined with percutaneous Achilles tendon lengthening , with measurements made before and after treatment , at the seven-month follow-up examination , and at the final follow-up evaluation ( a mean [ and st and ard deviation ] of 2.1 + /- 0.7 years after initial healing ) . There were thirty-three subjects in the total-contact cast group and thirty-one subjects in the Achilles tendon lengthening group . There were no significant differences in age , body-mass index , or duration of diabetes between the groups . Outcome measures were time to healing of the ulcer , ulcer recurrence rate , range of dorsiflexion of the ankle , peak torque ( strength ) of the plantar flexor muscles , and peak plantar pressures on the forefoot . RESULTS Twenty-nine ( 88 % ) of thirty-three ulcers in the total-contact cast group and all thirty ulcers ( 100 % ) in the Achilles tendon lengthening group healed after a mean duration ( and st and ard deviation ) of 41 + /- 28 days and 58 + /- 47 days , respectively ( p > 0.05 ) . ( One patient in the Achilles tendon lengthening group died before treatment was completed . ) In the first seven months of follow-up , sixteen ( 59 % ) of the twenty-seven patients in the total-contact cast group who were available for follow-up and four ( 15 % ) of the twenty-seven patients in the Achilles tendon lengthening group who were available for follow-up had an ulcer recurrence ( p = 0.001 ) . At the time of the two-year follow-up , twenty-one ( 81 % ) of the twenty-six patients in the total-contact cast group and ten ( 38 % ) of the twenty-six patients in the Achilles tendon lengthening group had ulcer recurrence ( p = 0.002 ) . Compared with the group treated with the total-contact cast , the group treated with Achilles tendon lengthening had increased dorsiflexion and it remained increased at seven months ( p < 0.001 ) . Plantar flexor peak torque also decreased after Achilles tendon lengthening ( p < 0.004 ) , but it returned to baseline after seven months . Peak plantar pressures on the forefoot during barefoot walking were reduced ( p < 0.0002 ) following Achilles tendon lengthening yet returned to baseline values within seven months after treatment . CONCLUSIONS All ulcers healed in the Achilles tendon lengthening group , and the risk for ulcer recurrence was 75 % less at seven months and 52 % less at two years than that in the total-contact cast group . Achilles tendon lengthening should be considered an effective strategy to reduce recurrence of neuropathic ulceration of the plantar aspect of the forefoot in patients with diabetes mellitus and limited ankle dorsiflexion ( < /=5 degrees ) OBJECTIVE To compare the efficacy , safety , and compliance of a nonremovable fiberglass cast boot and off-loading shoes in the treatment of diabetic plantar ulcers . RESEARCH DESIGN AND METHODS Patients ( n = 93 ) with noninfected , nonischemic plantar ulcers were included in this prospect i ve nonr and omized study . Treatment used a nonremovable fiberglass cast boot for longer st and ing and deeper ulcers ( n = 42 ) and a half shoe or heel-relief shoe for other ulcers ( n = 51 ) . We evaluated off-loading therapy , compliance , and complications in both groups . RESULTS The healing rate was significantly higher with the cast boot than with the off-loading shoe ( 81 vs. 70 % , P = 0.017 ) , with healing times of 68.6 + /- 35.1 vs. 134.2 + /- 133.0 days , respectively , and hazard ratio 1.68 ( 95 % CI 1.04 - 2.70 ) ; complete compliance with treatment was 98 vs. 10 % ( P = 0.001 ) , respectively . Secondary osteomyelitis developed in 3 patients in the cast boot group and 13 patients in the off-loading shoe group ( P = 0.026 ) . CONCLUSIONS A nonremovable fiberglass cast boot was effective in healing diabetic plantar ulcers and in decreasing the risk of secondary osteomyelitis . The cast boot forced compliance with off-loading , thus promoting healing Abstract . Aims /hypothesis : The management of charcot neuroarthropathy , a severe disabling condition in diabetic patients with peripheral neuropathy , is currently inadequate with no specific pharmacological treatment available . We undertook a double-blind r and omised controlled trial to study the effect of pamidronate , a bisphosphonate , in the management of acute diabetic Charcot neuroarthropathy . Methods : Altogether 39 diabetic patients with active Charcot neuroarthropathy from four centres in Engl and were r and omised in a double-blind placebo-controlled trial . Patients received a single infusion of 90 mg of pamidronate or placebo ( saline ) . Foot temperatures , symptoms and markers of bone turnover ( bone specific alkaline phosphatase and deoxypyridinoline crosslinks ) were measured over the 12 months , in 10 visits . All patients also had st and ard treatment of the Charcot foot . Results : Mean age of the study group ( 59 % Type II ( non-insulin-dependent ) diabetes mellitus ) was 56.3 ± 10.2 years . The mean temperature difference between active and control groups was 3.6 ± 1.7 ° C and 3.3 ± 1.4 ° C , respectively . There was a fall in temperature of the affected foot in both groups after 2 weeks with a further reduction in temperature in the active group at 4 weeks ( active and placebo vs baseline ; p = 0.001 ; p = 0.01 , respectively ) , but no difference was seen between groups . An improvement in symptoms was seen in the active group compared with the placebo group ( p < 0.001 ) . Reduction in bone turnover ( means ± SEM ) was greater in the active than in the control group . Urinary deoxypyridinoline in the pamidronate treated group fell to 4.4 ± 0.4 nmol/mmol creatinine at 4 weeks compared with 7.1 ± 1.0 in the placebo group ( p = 0.01 ) and bone-specific alkaline phosphatase fell to 14.1 ± 1.2 u/l compared with 18.6 ± 1.6 u/l after 4 weeks , respectively ( p = 0.03 ) . Conclusion /interpretation : The bisphosphonate , pamidronate , given as a single dose leads to a reduction in bone turnover , symptoms and disease activity in diabetic patients with active Charcot neuroarthropathy . [ Diabetologia ( 2001 ) 44 : 2032–2037 CONTEXT Many people with diabetes experience lower-limb ulcers . Footwear has been implicated as a primary cause of foot ulcers , yet research is limited on the efficacy of shoe and insert combinations to prevent reulceration . OBJECTIVE To determine whether extra-depth and -width therapeutic shoes used with 2 types of inserts reduce reulceration in diabetic individuals with a history of foot ulcer . DESIGN , SETTING , AND PARTICIPANTS R and omized clinical trial of 400 diabetes patients with history of foot ulcer in 2 Washington State health care organizations who did not require custom shoes for foot deformity and were enrolled between August 1997 and December 1998 and followed up for 2 years . Data collected at regular intervals documented physical , foot , and diabetes characteristics ; footwear use ; foot lesions ; and ulcers . INTERVENTIONS Participants were r and omly assigned to receive 3 pairs of therapeutic shoes and 3 pairs of customized medium-density cork inserts with a neoprene closed-cell cover ( n = 121 ) ; to receive 3 pairs of therapeutic shoes and 3 pairs of prefabricated , tapered polyurethane inserts with a brushed nylon cover ( n = 119 ) ; or to wear their usual footwear ( controls ; n = 160 ) . MAIN OUTCOME MEASURE Foot reulceration , compared among the 3 groups . RESULTS Two-year cumulative reulceration incidence across the 3 groups was low : 15 % in the cork-insert group , 14 % in the prefabricated-insert group , and 17 % in controls . In the intent-to-treat analysis , patients assigned to therapeutic shoes did not have a significantly lower risk of reulceration compared with controls ( risk ratio [ RR ] for the cork-insert group , 0.88 ; 95 % confidence interval [ CI ] , 0.51 - 1.52 and RR the for prefabricated-insert group , 0.85 ; 95 % CI , 0.48 - 1.48 ) . All ulcer episodes in patients assigned to therapeutic shoes and 88 % wearing non study shoes occurred in patients with foot insensitivity . CONCLUSIONS This study of persons without severe foot deformity does not provide evidence to support widespread dispensing of therapeutic shoes and inserts to diabetic patients with a history of foot ulcer . Study shoes and custom cork or preformed polyurethane inserts conferred no significant ulcer reduction compared with control footwear . This study suggests that careful attention to foot care by health care professionals may be more important than therapeutic footwear but does not negate the possibility that special footwear is beneficial in persons with diabetes who do not receive such close attention to foot care by their health care providers or in individuals with severe foot deformities This study was design ed to assess the value of combined magnetic field ( CMF ) bone growth stimulation in the treatment of acute , phase 1 , Charcot neuroarthopathy . Thirty-one subjects were studied . Initially 10 controls and 11 study patients were examined . When the initial results were analyzed , 10 additional study patients were added . The result was a statistically significant reduction in time to consolidation , 23.8 weeks for the control versus 11 weeks for the study group . Additionally , less destruction of the bony architecture was noted in the study group as compared to the control . Thus the results of this exp and ed pilot study demonstrate the efficacy of CMF in accelerating the consolidation process of acute , phase 1 , Charcot joint , and decreasing the amount of residual deformity |
1,612 | 23,777,875 | Studies with Nigella Sativa , Camellia Sinensis , Crocus Sativus L , Seaweed laminaria Digitata , Xantigen , virgin olive oil , Catechin enriched green tea , Monoselect Camellia , Oolong tea , Yacon syrup , Irvingia Gabonensi , Weighlevel , RCM-104 compound of Camellia Sinensis , Pistachio , Psyllium fibre , black Chinese tea , sea buckthorn and bilberries show significant decreases in body weight .
Only , alginate-based brown seaweed and Laminaria Digitata caused an abdominal bloating and upper respiratory tract infection as the side effect in the trial group .
In conclusion , Nigella Sativa , Camellia Synensis , Green Tea , and Black Chinese Tea seem to have satisfactory anti-obesity effects . | Obesity is the most prevalent health problem affecting all age groups , and leads to many complications in the form of chronic heart disease , diabetes mellitus Type 2 and stroke . | Objectives : Drinking green tea is associated with many health benefits , including increased fat oxidation . We tested the hypothesis that epigallocatechin-3-gallate ( EGCG ) , the main green tea catechin , increases fat oxidation in obese men . Methods : Ten healthy overweight/obese males ( body mass index 31.3±0.8 kg/m2 ) were studied in a r and omized , placebo-controlled , double-blind crossover trial . Study supplements were low EGCG ( 300 mg ) , high EGCG ( 600 mg ) , caffeine ( 200 mg ) , EGCG/caffeine ( 300 mg/200 mg ) or placebo and were taken orally for 3 days . At the third day of supplementation , O2 consumption and CO2 production was measured by indirect calorimetry to assess energy expenditure and fat oxidation over 4 h each after overnight fasting and after a st and ardized test meal . Results : Energy expenditure was not affected by any supplementation , neither after overnight fasting nor after the test meal . During the first 2 h after overnight fasting , fat oxidation increased by 7.7 ( not significant , NS ) , 15.2 ( NS ) , 26.3 ( P<0.05 vs placebo ) and 35.4 % ( P<0.01 vs placebo and low EGCG ) , for low EGCG , high EGCG , caffeine and EGCG/caffeine , respectively . During the first 2 h after the meal , the mean increase in fat oxidation was 33.3 ( P<0.05 vs placebo ) , 20.2 ( NS ) , 34.5 ( P<0.05 vs placebo ) and 49.4 % ( P<0.05 vs placebo ) for low EGCG , high EGCG , caffeine and EGCG/caffeine , respectively . Conclusions : Low EGCG increases postpr and ial fat oxidation in obese men and this to the same extent as 200 mg caffeine , whereas high EGCG does not exert this effect . Fasting fat oxidation is increased only by caffeine ( with or without EGCG ) . There is no synergism of low EGCG and 200 mg caffeine . Energy expenditure is not affected by EGCG Lack of control of food intake , excess size , and frequency of meals are critical to the development of obesity . The stomach signals satiation postpr and ially and may play an important role in control of calorie intake . Sodium alginate ( based on brown seaweed Laminaria digitata ) is currently marketed as a weight loss supplement , but its effects on gastric motor functions and satiation are unknown . We evaluated effects of 10 days treatment with alginate or placebo on gastric functions , satiation , appetite , and gut hormones associated with satiety in overweight or obese adults . We conducted a r and omized , 1:1 , placebo-controlled , allocation-concealed study in 48 overweight or obese participants with excluded psychiatric comorbidity and binge eating disorder . All underwent measurements of gastric emptying ( GE ) , fasting , and postpr and ial gastric volumes ( GVs ) , postpr and ial satiation , calorie intake at a free choice meal and selected gut hormones after 1 week of alginate ( three capsules vs. matching placebo per day , ingested 30 min before the main meal ) . Six capsules were ingested with water 30 min before the GE , GV , and satiation tests on days 8 - 10 . There were no treatment group effects on GE or volumes , gut hormones ( ghrelin , cholecystokinin ( CCK ) , glucagon-like peptide-1 ( GLP-1 ) , peptide YY ( PYY ) ) , satiation , total and macronutrient calorie intake at a free choice meal . There was no difference detected in results between obese and overweight patients . Alginate treatment for a period of 10 days showed no effect on gastric motor functions , satiation , appetite , or gut hormones . These results question the use of short-term alginate treatment for weight loss Snacking is an uncontrolled eating behavior , predisposing weight gain and obesity . It primarily affects the female population and is frequently associated with stress . We hypothesized that oral supplementation with Satiereal ( Inoreal Ltd , Plerin , France ) , a novel extract of saffron stigma , may reduce snacking and enhance satiety through its suggested mood-improving effect , and thus contribute to weight loss . Healthy , mildly overweight women ( N = 60 ) participated in this r and omized , placebo-controlled , double-blind study that evaluated the efficacy of Satiereal supplementation on body weight changes over an 8-week period . Snacking frequency , the main secondary variable , was assessed by daily self-recording of episodes by the subjects in a nutrition diary . Twice a day , enrolled subjects consumed 1 capsule of Satiereal ( 176.5 mg extract per day ( n = 31 ) or a matching placebo ( n = 29 ) . Caloric intake was left unrestricted during the study . At baseline , both groups were homogeneous for age , body weight , and snacking frequency . Satiereal caused a significantly greater body weight reduction than placebo after 8 weeks ( P < .01 ) . The mean snacking frequency was significantly decreased in the Satiereal group as compared with the placebo group ( P < .05 ) . Other anthropometric dimensions and vital signs remained almost unchanged in both groups . No subject withdrawal attributable to a product effect was reported throughout the trial , suggesting a good tolerability to Satiereal . Our results indicate that Satiereal consumption produces a reduction of snacking and creates a satiating effect that could contribute to body weight loss . The combination of an adequate diet with Satiereal supplementation might help subjects engaged in a weight loss program in achieving their objective OBJECTIVE Peptide YY3–36 ( PYY3–36 ) , a Y2 receptor agonist , and oxyntomodulin , a glucagon-like peptide 1 ( GLP-1 ) receptor agonist , are cosecreted by intestinal L-cells after each meal . Separately each hormone acts as an endogenous satiety signal and reduces appetite in humans when infused intravenously . The aim of the current study was to investigate whether the anorectic effects of PYY3–36 and oxyntomodulin can be additive . RESEARCH DESIGN AND METHODS Twelve overweight or obese human volunteers underwent a r and omized , double-blinded , placebo-controlled study . An ad libitum test meal was used to measure energy intake during intravenous infusions of either PYY3–36 or oxyntomodulin or combined PYY3–36/oxyntomodulin . RESULTS Energy intake during coadministration of PYY3–36 and oxyntomodulin was reduced by 42.7 % in comparison with the saline control and was significantly lower than that during infusions of either hormone alone . CONCLUSIONS The anorectic effects of PYY3–36 and oxyntomodulin can be additive in overweight and obese humans . Coadministration of Y2 receptor agonists and GLP-1 receptor agonists may be a useful treatment strategy for obesity Our objective was to examine the effect of a quercetin supplementation on blood pressure , lipid metabolism , markers of oxidative stress , inflammation , and body composition in an at-risk population of 93 overweight-obese volunteers aged 25 - 65 y with metabolic syndrome traits in relation to apolipoprotein ( apo ) E genotype . Participants were r and omized to receive 150 mg/d quercetin in a double-blinded , placebo-controlled , crossover trial with 6-wk treatment periods separated by a 5-wk washout period . Retrospectively , 5 apoE genotype variants were found ( epsilon2/epsilon3 , n = 3 ; epsilon3/epsilon3 , n = 60 ; epsilon3/epsilon4 , n = 23 ; epsilon2/epsilon4 , n = 4 ; and epsilon4/epsilon4 , n = 3 ) . Participants were classified into the following 3 apoE phenotypes : apoE2 ( n = 3 ) , apoE3 ( n = 60 ) , and apoE4 ( n = 26 ) . Data were analyzed for apoE3 and apoE4 subgroups . Quercetin decreased systolic blood pressure by 3.4 mm Hg ( P < 0.01 ) in the apoE3 group , whereas no significant effect was observed in the apoE4 group . Quercetin decreased serum HDL cholesterol ( P < 0.01 ) and apoA1 ( P < 0.01 ) and increased the LDL : HDL cholesterol ratio ( P < 0.05 ) in the apoE4 subgroup , whereas the apoE3 subgroup had no significant changes in these variables . Quercetin significantly decreased plasma oxidized LDL and tumor necrosis factor-alpha in the apoE3 and apoE4 groups , whereas no significant inter-group differences were found . Serum C-reactive protein and nutritional status ( body weight , waist circumference , fat mass , fat-free mass ) were unaffected compared with placebo . In conclusion , quercetin exhibited blood pressure-lowering effects in overweight-obese carriers of the apo epsilon3/epsilon3 genotype but not in carriers of the epsilon4 allele . Furthermore , quercetin supplementation result ed in a reduction in HDL cholesterol and apoA1 in apo epsilon4 carriers OBJECTIVE To assess the effects of exenatide on body weight and glucose tolerance in nondiabetic obese subjects with normal or impaired glucose tolerance ( IGT ) or impaired fasting glucose ( IFG ) . RESEARCH DESIGN AND METHODS Obese subjects ( n = 152 ; age 46 ± 12 years , female 82 % , weight 108.6 ± 23.0 kg , BMI 39.6 ± 7.0 kg/m2 , IGT or IFG 25 % ) were r and omized to receive exenatide ( n = 73 ) or placebo ( n = 79 ) , along with lifestyle intervention , for 24 weeks . RESULTS Exenatide-treated subjects lost 5.1 ± 0.5 kg from baseline versus 1.6 ± 0.5 kg with placebo ( exenatide − placebo , P < 0.001 ) . Placebo-subtracted difference in percent weight reduction was −3.3 ± 0.5 % ( P < 0.001 ) . Both groups reduced their daily calorie intake ( exenatide , −449 cal ; placebo , −387 cal ) . IGT or IFG normalized at end point in 77 and 56 % of exenatide and placebo subjects , respectively . CONCLUSIONS Exenatide plus lifestyle modification decreased caloric intake and result ed in weight loss in nondiabetic obesity with improved glucose tolerance in subjects with IGT and IFG In vitro and in vivo studies have shown that punicic acid , a type of conjugated fatty acid and the main constituent of pomegranate seed oil ( PSO ) , has anti-atherogenic effects . The present study aim ed at determining the effect of PSO treatment on serum lipid profiles . This double-blind placebo-controlled r and omised clinical trial included fifty-one hyperlipidaemic subjects , diagnosed according to National Cholesterol Education Program definition , and r and omly assigned to the PSO and the control groups . The PSO and placebo groups received 400 mg PSO and placebo twice daily , respectively and were followed up for 4 weeks . Serum concentrations of lipids and lipoproteins were measured before and 4 weeks after intervention . Mean concentration of TAG and the TAG : HDL cholesterol ( HDL-C ) ratio were significantly decreased after 4 weeks in the PSO group as compared with baseline values ( 2.75 ( sd 1.40 ) v. 3.45 ( sd 1.56 ) mmol/l , P = 0.009 and 5.7 ( sd 4.6 ) v. 7.5 ( sd 5.0 ) , P = 0.031 , respectively ) . The treatment effect was statistically significant in the PSO group as compared with controls in diminution of cholesterol : HDL-C ratio ( 5.4 ( sd 1.5 ) v. 5.9 ( sd 1.4 ) , P < 0.05 ) adjusted for baseline values . We found a mean difference for PSO v. placebo in HDL-C concentration ( 0.13 v. - 0.02 mmol/l ) and cholesterol : HDL-C ratio ( - 0.42 v. 0.01 , P < 0.05 ) . Serum cholesterol , LDL cholesterol and glucose concentrations and body composition variables remained unchanged . It is concluded that administration of PSO for 4 weeks in hyperlipidaemic subjects had favourable effects on lipid profiles including TAG and TAG : HDL-C ratio Dietary supplementation with whole blueberries in a pre clinical study result ed in a reduction in glucose concentrations over time . We sought to evaluate the effect of daily dietary supplementation with bioactives from blueberries on whole-body insulin sensitivity in men and women . A double-blinded , r and omized , and placebo-controlled clinical study design was used . After screening to resolve study eligibility , baseline ( wk 0 ) insulin sensitivity was measured on 32 obese , nondiabetic , and insulin-resistant subjects using a high-dose hyperinsulinemic-euglycemic clamp ( insulin infusion of 120 mU(861 pmol)⋅m(-2)⋅min(-1 ) ) . Serum inflammatory biomarkers and adiposity were measured at baseline . At the end of the study , insulin sensitivity , inflammatory biomarkers , and adiposity were reassessed . Participants were r and omized to consume either a smoothie containing 22.5 g blueberry bioactives ( blueberry group , n = 15 ) or a smoothie of equal nutritional value without added blueberry bioactives ( placebo group , n = 17 ) twice daily for 6 wk . Both groups were instructed to maintain their body weight by reducing ad libitum intake by an amount equal to the energy intake of the smoothies . Participants ' body weights were evaluated weekly and 3-d food records were collected at baseline , the middle , and end of the study . The mean change in insulin sensitivity improved more in the blueberry group ( 1.7 ± 0.5 mg⋅kg FFM(-1)⋅min(-1 ) ) than in the placebo group ( 0.4 ± 0.4 mg⋅kg FFM(-1)⋅min(-1 ) ) ( P = 0.04 ) . Insulin sensitivity was enhanced in the blueberry group at the end of the study without significant changes in adiposity , energy intake , and inflammatory biomarkers . In conclusion , daily dietary supplementation with bioactives from whole blueberries improved insulin sensitivity in obese , nondiabetic , and insulin-resistant participants Purpose Fenugreek seeds ( Trigonella foenum-graecum L. ) have long been used as a herbal medicine for treating metabolic and nutritive dysfunctions . They have been shown to modulate feeding behaviour in animals . We have recently observed a selective decrease in fat consumption in healthy normal weight volunteers treated with a hydro-alcoholic seed extract . However , strong clinical data on the effects of fenugreek seeds on energy intake are lacking , especially in overweight individuals . The aim of our study was to investigate the effects of a repeated administration of a fenugreek seed extract on the eating behaviour of overweight subjects . Methods Thirty-nine healthy overweight male volunteers completed a 6-week double-blind r and omized placebo-controlled parallel trial of a fixed dose of a fenugreek seed extract . Main endpoints were energy intake ( dietary records and meal test ) , weight , fasting and post-absorptive glucose and insulin , appetite/satiety scores and oxidative parameters . Results Daily fat consumption , expressed as the ratio fat reported energy intake/total energy expenditure ( fat-REI/TEE ) , was significantly decreased in our overweight subjects administered the fenugreek seed extract relative to those receiving the placebo ( fat-REI/TEE 0.26 ± 0.02 vs. 0.30 ± 0.01 , respectively ; P = 0.032 ) . We also observed a significant decrease in the insulin/glucose ratio in subjects treated with fenugreek seed extract relative to the placebo group ( 0.89 ± 0.09 vs. 1.06 ± 0.10 mUI mmol−1 , respectively ; P = 0.044 ) . No significant effect was observed on weight , appetite/satiety scores or oxidative parameters . Conclusion The repeated administration of a fenugreek seed extract slightly but significantly decreased dietary fat consumption in healthy overweight subjects in this short-term study BACKGROUND Although modifiable cardiovascular disease risk factors are common , some patients eschew conventional drug treatments in favor of natural alternatives . Pine bark extract , a dietary supplement source of antioxidant oligomeric proanthocyanidin complexes , has multiple putative cardiovascular benefits . Studies published to date about the supplement have notable method ological limitations . METHODS We r and omized 130 individuals with increased cardiovascular disease risk to take 200 mg of a water-based extract of pine bark ( n = 64 ; Toyo-FVG , Toyo Bio-Pharma , Torrance , California ; Shinyaku Co , Ltd , Saga , Japan ; also marketed as Flavagenol in Japan ) or placebo ( n = 66 ) once per day . Blood pressure , our primary outcome , and other cardiovascular disease risk factors were measured at baseline and at 6 and 12 weeks . Statistical analyses were conducted using regression models . RESULTS Baseline characteristics did not differ between the study groups . Over the 12-week intervention , the sum of systolic and diastolic blood pressures decreased by 1.0 mm Hg ( 95 % confidence interval , -4.2 to 2.1 mm Hg ) in the pine bark extract-treated group and by 1.9 mm Hg ( -5.5 to 1.7 mm Hg ) in the placebo group ( P = .87 ) . Other outcomes were likewise not significantly different , including body mass index , lipid panel measures , liver transaminase test results , lipoprotein cholesterol particle size , and levels of insulin , lipoprotein(a ) , fasting glucose , and high-sensitivity C-reactive protein . There were no subgroups for whom intake of pine bark extract affected cardiovascular disease risk factors . CONCLUSIONS This pine bark extract ( at a dosage of 200 mg/d ) was safe but was not associated with improvement in cardiovascular disease risk factors . Although variations among participants , dosages , and chemical preparations could contribute to different findings compared with past studies , our results are consistent with a general failure of antioxidants to demonstrate cardiovascular benefits . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00425945 AIM OF THE STUDY The aim of this study was to evaluate the acute and chronic effects of OpunDia ( Opuntia ficus-indica ) in obese pre-diabetic men and women . MATERIAL S AND METHODS This double-blind placebo controlled study included participants ( age range of 20 - 50 years ) r and omly assigned to one of the two groups and given a 16-week supply of either the 200 mg OpunDia ( n=15 ) , or placebo ( n=14 ) . The acute phase of the study consisted of an oral glucose tolerance test ( OGTT ) with a 400 mg bolus of OpunDia given 30 min before orally ingesting a 75 g glucose drink . Baseline and post 16-week concentrations of glucose , insulin , hsCRP , adiponectin , proinsulin , Hb1Ac , cholesterol , and a comprehensive metabolic panel were collected along with body composition measured via densitometry ( BOD POD ) . A repeated measures ANOVA was conducted to determine any significant interactions between group and time . Follow-up analysis was performed to determine differences among groups at each time point . Paired t-tests were performed on all variables to determine if any within group differences existed across time . RESULTS There was a statistically significant decrease ( P<0.05 ) in the blood glucose concentrations at the 60 ( 205.92+/-36.90 and 188.84+/-38.43 mg/dL , respectively ) , 90 ( 184.55+/-33.67 and 169.74+/-35.16 mg/dL , respectively ) and 120 min ( 159.24+/-17.85 and 148.89+/-24.86 mg/dL , respectively ) time points with the pre-OGTT compared to the OpunDia bolus trial . There were no between-group differences found with the OGTT time points , area under the curve , blood chemistry variables ( insulin , hsCRP , adiponectin , proinsulin , Hb1Ac ) , diet analysis variables ( carbohydrates , fat , protein and total kcals ) , body composition variables ( fat mass , fat free mass , percent body fat and total body weight ) , or blood chemistry safety parameters ( comprehensive metabolic panel ) pre-to-post 16-week intervention . CONCLUSIONS This study shows the acute blood glucose lowering effects and the long-term safety of the proprietary product OpunDia , thus supporting the traditional use of Opuntia ficus-indica for blood glucose management CONTEXT Lorcaserin is a novel selective agonist of the serotonin 2C receptor . OBJECTIVE Our objective was to evaluate the effects of lorcaserin on body weight , cardiovascular risk factors , and safety in obese and overweight patients . DESIGN AND SETTING This r and omized , placebo-controlled , double-blind , parallel arm trial took place at 97 U.S. research centers . PATIENTS Patients included 4008 patients , aged 18 - 65 yr , with a body mass index between 30 and 45 kg/m(2 ) or between 27 and 29.9 kg/m(2 ) with an obesity-related comorbid condition . INTERVENTIONS Patients were r and omly assigned in a 2:1:2 ratio to receive lorcaserin 10 mg twice daily ( BID ) , lorcaserin 10 mg once daily ( QD ) , or placebo . All patients received diet and exercise counseling . MAIN OUTCOME MEASURES The ordered primary endpoints were proportion of patients achieving at least 5 % reduction in body weight , mean change in body weight , and proportion of patients achieving at least 10 % reduction in body weight at 1 yr . Serial echocardiograms monitored heart valve function . RESULTS Significantly more patients treated with lorcaserin 10 mg BID and QD lost at least 5 % of baseline body weight ( 47.2 and 40.2 % , respectively ) as compared with placebo ( 25.0 % , P < 0.001 vs. lorcaserin BID ) . Least squares mean ( 95 % confidence interval ) weight loss with lorcaserin BID and QD was 5.8 % ( 5.5 - 6.2 % ) and 4.7 % ( 4.3 - 5.2 % ) , respectively , compared with 2.8 % ( 2.5 - 3.2 % ) with placebo ( P < 0.001 vs. lorcaserin BID ; least squares mean difference , 3.0 % ) . Weight loss of at least 10 % was achieved by 22.6 and 17.4 % of patients receiving lorcaserin 10 mg BID and QD , respectively , and 9.7 % of patients in the placebo group ( P < 0.001 vs. lorcaserin BID ) . Headache , nausea , and dizziness were the most common lorcaserin-related adverse events . U.S. Food and Drug Administration-defined echocardiographic valvulopathy occurred in 2.0 % of patients on placebo and 2.0 % on lorcaserin 10 mg BID . CONCLUSIONS Lorcaserin administered in conjunction with a lifestyle modification program was associated with dose-dependent weight loss that was significantly greater than with placebo Water-soluble black Chinese ( Pu-Erh ) tea extract ( BTE ) , which contains high gallic acid content , has been demonstrated to elicit antiobese effects in animals . Because gallic acid is related with the reduction of visceral fat and cholesterol contents and improvement of obesity in animals , we investigated the effects of BTE intake on 36 preobese Japanese adults ( body mass index [ BMI ] , > 25- < 30 kg/m(2 ) ) in a 12-week double-blind , r and omized , placebo-controlled group comparison study using powdered barley tea with or without ( placebo ) BTE . A follow-up 4-week period after BTE intake termination was monitored to observe the withdrawal effect . All subjects ingested barley tea with or without BTE ( 333 mg ) before each of the 3 daily meals . In the BTE-treated group , the mean pretreament values of body weight and BMI significantly decreased after intake and after BTE withdrawal . However , the corresponding values scored significant differences only from 8 weeks after intake ( vs the placebo-treated group ) . The mean values of the waist circumference indicated a similar tendency . Furthermore , coronal navel section ( same anatomical position ) images of computed tomography of all BTE- and non-BTE-treated subjects revealed that the visceral fat areas ( cm(2 ) ) were significantly ( P < .05 ) less in the former 12 weeks after BTE ingestion . Measured biochemical parameters did not indicate significant differences , and BTE-treated subjects did not complain of any adverse effects ( abdominal distension , etc ) . Ingestion of BTE exhibited significant effects in reducing the mean waist circumference , BMI , and visceral fat values and might be useful for weight control and prevention of obesity development ( or metabolic syndrome ) in humans Objective To determine the anti-obesity effects of oolong tea on diet-induced overweight or obesity . Methods A total of 8 g of oolong tea a day for 6 weeks was ingested by 102 diet-induced overweight or obese subjects . The body fat level of the subjects was determined at the same time by taking body weight , height and waist measurements . The thickness of the subcutaneous fat layer was also determined on the abdomen 3 cm to the right of the navel by the ultrasonic echo method . On the other h and , effects of oolong tea ingestion on plasma triglyceride ( TG ) and total cholesterol ( TC ) were determined . Inhibitions of pancreatic lipase by oolong tea extract and catechins in vitro were also determined . Results A total of 70 % of the severely obese subjects did show a decrease of more than 1 kg in body weight , including 22 % who lost more than 3 kg . Similarly , 64 % of the obese subjects and 66 % of the overweight subjects lost more than 1 kg during the experiment , and the subcutaneous fat content decreased in 12 % of the subjects . The correlation between weight loss and subcutaneous fat decrease in men ( r=0.055 ) was obviously lower than that in women ( r=0.440 , P<0.01 ) . Body weight loss was signifificantly related to the decrease of the waist size in men ( r=0.730 , P<0.01 ) and women ( r=0.480 , P<0.01 ) . Also , the correlation between subcutaneous fat reduction and decreased waist size was signifificant in women ( r=0.554 , P<0.01 ) , but not in men ( r=0.050 , P>0.05 ) . Moreover , the plasma levels of TG and TC of the subjects with hyperlipidemia were remarkably decreased after ingesting oolong tea for 6 weeks . In vitro assays for the inhibition of pancreatic lipase by oolong tea extract and catechins suggest that the mechanism for oolong tea to prevent hyperlipidemia may be related to the regulative action of oolong tea catechins in lipoprotein activity . Conclusions Oolong tea could decrease body fat content and reduce body weight through improving lipid metabolism . Chronic consumption of oolong tea may prevent against obesity Background / Objectives : The aim of this study was to analyze the influence of a Mediterranean dietary pattern on plasma total antioxidant capacity ( TAC ) after 3 years of intervention and the associations with adiposity indexes in a r and omized dietary trial ( PREDIMED trial ) with high cardiovascular risk patients .Subjects/ Methods : 187 subjects were r and omly selected from the PREDIMED-UNAV center after they completed 3-year intervention program . Participants were following a Mediterranean-style diet with high intake of virgin olive oil or high intake of nuts , or a conventional low-fat diet . Adiposity indexes were measured at baseline and at year 3 . Plasma TAC was evaluated using a commercially available colorimetric assay kit . Results : Plasma TAC in the control , olive oil and nuts groups was 2.01±0.15 , 3.51±0.14 and 3.02±0.14 mM Trolox , respectively after adjusting for age and sex . The differences between the Mediterranean diet and control groups were statistically significant ( P<0.001 ) . Moreover higher levels of TAC were significantly associated with a reduction in body weight after 3 years of intervention among subjects allocated to the virgin olive oil group ( B=−1.306 ; 95 % CI=−2.439 to −0.173 ; P=0.025 , after adjusting for age , sex and baseline body mass index ) . Conclusions : Mediterranean diet , especially rich in virgin olive oil , is associated with higher levels of plasma antioxidant capacity . Plasma TAC is related to a reduction in body weight after 3 years of intervention in a high cardiovascular risk population with a Mediterranean-style diet rich in virgin olive oil Background : Wholegrain intake is inversely related to weight gain over time , but little information is available on the role of pulses in weight control . Objective : To compare weight loss , metabolic outcomes , and nutrient intakes in obese people assigned to a diet rich in pulses and wholegrains or a control diet . Methods : R and omized controlled study of 18 months with 113 volunteers ( body mass index [ BMI ] ≥ 28 kg/m2 ) . Diets were based on guidelines published by the National Heart Foundation of New Zeal and . The intervention group was advised to consume 2 serves of pulses and 4 serves of wholegrain foods per day as substitutions for more refined carbohydrates . Results : Fiber intakes were higher , intakes of several vitamins and minerals were better maintained , and dietary glycemic index was lower in the intervention compared with the control group . Mean ( st and ard error [ SE ] ) weight loss at 6 months was 6.0 ( 0.7 ) kg and 6.3 ( 0.6 ) kg in the control and intervention groups , respectively , and was not different between groups ( p > 0.05 ) . Blood pressure , triglycerides , and glycemic load were lowered in both groups compared with baseline . Waist circumference was decreased at 18 months in the intervention compared with the control group ( −2.8 cm ; 95 % confidence interval [ CI ] : −0.4 , −5.1 ) . Conclusions : Incorporation of pulses and wholegrain foods into a weight loss program result ed in a greater reduction in waist circumference compared with the group consuming a control diet , although no difference in weight loss was noted between groups . Retention of several nutrients was better with the pulse and wholegrain diet Objective : There is a widely held view that , due to high fat content , snacking on nuts will lead to weight gain , ultimately causing unhealthy changes in lipid profiles . This study is design ed to study the effects of pistachio snack consumption on body weight and lipid levels in obese participants under real-world conditions . Methods : Participants were r and omly assigned to consume 1 of 2 isocaloric weight reduction diets for 12 weeks , with each providing 500 cal per day less than resting metabolic rate . Each diet included an afternoon snack of either 53 g ( 240 cal ) of salted pistachios ( n = 31 ) or 56 g of salted pretzels ( 220 cal ; n = 28 ) . Results : Both groups lost weight during the 12-week study ( time trend , p < 0.001 ) , but there were significant differences in the changes in body mass index between the pretzel and pistachio groups ( pistachio , 30.1 ± 0.4 to 28.8 ± 0.4 vs. pretzel , 30.9 ± 0.4 to 30.3 ± 0.5 ) . At 6 and 12 weeks , triglycerides were significantly lower in the pistachio group compared with the pretzel group ( 88.04 ± 9.80 mg/dL vs. 144.56 ± 18.86 mg/dL , p = 0.01 at 6 weeks and 88.10 ± 6.78 mg/dL vs. 132.15 ± 16.76 mg/dL , p = 0.02 at 12 weeks ) , and there was a time trend difference between the 2 groups over the 12 weeks ( p < 0.01 ) . There were no significant differences in total cholesterol , high-density lipoprotein cholesterol , low-density lipoprotein cholesterol , insulin , or glucose between the 2 groups . Conclusion : Pistachios can be consumed as a portion-controlled snack for individuals restricting calories to lose weight without concern that pistachios will cause weight gain . By comparison to refined carbohydrate snacks such as pretzels , pistachios may have beneficial effects on triglycerides as well Eighteen healthy obese subjects participated in a single blind , r and omized , crossover study of three test breakfasts , containing 0 g ( control ) , 4 g or 8 g of isolated fenugreek fiber . Subjects recorded ratings of hunger , satiety , fullness and prospect i ve food consumption using visual analog scales ( VAS ) every 30 min for 3.5 h. Postpr and ial blood glucose and insulin responses were measured . Energy intake from an ad libitum lunch buffet and for the remainder of the day was assessed . The 8 g dose of fenugreek fiber significantly increased mean ratings of satiety and fullness , and reduced ratings of hunger and prospect i ve food consumption ( P < 0.05 ) . Palatability was significantly reduced with increasing doses of fenugreek fiber ( P < 0.05 ) . No differences were observed for area under the curve ( AUC ) for blood glucose among treatments . An increase in insulin AUC was found with 8 g fenugreek fiber . Energy intake at an ad libitum lunch buffet was significantly lower for 8 g than 4 g fenugreek fiber , but not significantly different from control , although there was a trend towards a lower intake ( p = 0.11 ) . No differences were observed for energy intake for the remainder of the day . Fenugreek fiber ( 8 g ) significantly increased satiety and reduced energy intake at lunch , suggesting it may have short-term beneficial effects in obese subjects . Satiety results were not related to postpr and ial blood glucose Background : Lycium barbarum ( L. barbarum ) , a traditional Asian medicinal therapy for diabetes and other conditions , has been shown to increase metabolic rate and to reduce body-weight gains in rodent models , as well as to produce clinical improvements in general feelings of well-being including energy level . Objective : To investigate the impact of L. barbarum consumption on ( 1 ) caloric expenditure and ( 2 ) changes in morphometric parameters ( waist circumference ) in healthy human adults . Method : Two separate r and omized , double-blind , placebo-controlled , small clinical studies were conducted using a st and ardized L. barbarum fruit juice , GoChi , and assessing its effects on ( 1 ) resting metabolic rate ( RMR ) and postpr and ial energy expenditure ( PPEE ) as measured by indirect calorimetry after single-bolus intake of 3 doses of L. barbarum ( 30 , 60 , and 120 ml ) and placebo ; and ( 2 ) waist circumference and other morphometric changes in a 14-day intervention trial ( 120-ml daily intake ) in the subjects ( age = 34 years , body mass index = 29 kg/m2 ) . Results : ( 1 ) A single bolus of L. barbarum intake increased PPEE 1 through 4 hours postintake over the baseline level in a dose-dependent manner and was significantly higher than the placebo group by 10 % at 1 hour postintake of 120 ml ( p < 0.05 ) . ( 2 ) In a 14-day intervention trial , L. barbarum was found to significantly decrease waist circumference by 5.5 ± 0.8 cm ( n = 15 ) compared with the preintervention measurements and placebo group at postintervention day 15 ( p < 0.01 ) . By contrast , the changes in the placebo group ( n = 14 ) from pre interventions was 0.9 ± 0.8 cm , which was not statistically significant . Conclusions : These results show that L. barbarum consumption increases metabolic rate and reduces the waist circumference , relative to placebo treated control subjects Obesity is a major health problem in the developed and developing world . Many " functional " foods and ingredients are advocated for their effects on body composition but few have consistent scientific support for their efficacy . However , an increasing amount of mechanistic and clinical evidence is building for green tea ( GT ) . This experiment was therefore undertaken to study the effects of a high-catechin GT on body composition in a moderately overweight Chinese population . In a r and omized placebo-controlled trial , 182 moderately overweight Chinese subjects , consumed either two servings of a control drink ( C ; 30 mg catechins , 10 mg caffeine/day ) , one serving of the control drink and one serving of an extra high-catechin GT1 ( 458 mg catechins , 104 mg caffeine/day ) , two servings of a high-catechin GT2 ( 468 mg catechins , 126 mg caffeine/day ) or two servings of the extra high-catechin GT3 ( 886 mg catechins , 198 mg caffeine/day ) for 90 days . Data were collected at 0 , 30 , 60 , and 90 days . We observed a decrease in estimated intra-abdominal fat ( IAF ) area of 5.6 cm(2 ) in the GT3 group . In addition , we found decreases of 1.9 cm in waist circumference and 1.2 kg body weight in the GT3 group vs. C ( P < 0.05 ) . We also observed reductions in total body fat ( GT2 , 0.7 kg , P < 0.05 ) and body fat % ( GT1 , 0.6 % , P < 0.05 ) . We conclude that consumption of two servings of an extra high-catechin GT leads to improvements in body composition and reduces abdominal fatness in moderately overweight Chinese subjects OBJECTIVE The seed extracts from Nigella sativa is used by Unani physicians of traditional medicine ( Hakims or Tabibs ) and Ayurvedic practitioners ( Vaids ) in the treatment of several medical disorders including dyslipidemia , obesity , and hypertension . It is , therefore , important to prove or disprove the effectiveness , safety , and tolerability of powdered N. sativa ( Kalonji ) seed in capsules on serum lipid levels , blood sugar , blood pressure , and body weight in adults . DESIGN The study design was a r and omized , double-blind trial . SETTING S/LOCATION Conducted at Aga Khan University Hospital , Karachi , from February 2006 to January 2007 . SUBJECTS Half of the respondents received powdered N. sativa ( Kalonji ) seed in capsule and the rest received a placebo . INTERVENTION/ OUTCOME Baseline and after-intervention variables recorded were the following : body-mass index , waist-hip ratio , blood pressure , fasting blood sugar , serum lipids , serum alanine aminotransferase , and serum creatinine . RESULTS One hundred and twenty-three ( 123 ) patients were recruited . Sixty-four ( 64 ) and 59 patients were r and omized to the intervention and the control arms , respectively . Thirty-nine ( 39 ) patients in the intervention group and 34 in the control group completed the study . Favorable impact of powdered N. sativa ( Kalonji ) seed in capsule was noted on almost all variables , but results were not statistically significant because of small sample size . CONCLUSIONS Favorable impact of powdered N. sativa ( Kalonji ) seed in capsule was noted on almost all variables , but results were not statistically significant . A larger study with adequate sample size is recommended |
1,613 | 26,253,336 | Results revealed a high prevalence of pain in outpatient mini-hysteroscopy .
Conclusions Office mini-hysteroscopy is painful | Abstract Background Mini-hysteroscopy is believed to be pain-free or in the least bearable .
Office procedures are therefore usually performed without analgesia or anesthesia .
Is it indeed as tolerable as papers and authors suggest ?
Objectives To estimate what proportion of women reports moderate to severe discomfort during examination using the smaller diameter scopes . | OBJECTIVE To assess whether IV tramadol before outpatient hysteroscopy could reduce procedure-related pain . DESIGN A r and omized double-blind placebo controlled trial . SETTING Outpatient Hysteroscopy Centre in the Department of Obstetrics and Gynaecology of Cagliari University . PATIENT(S ) Fifty healthy , parous , women who underwent outpatient diagnostic hysteroscopy and endometrial biopsy . INTERVENTION(S ) R and om IV infusion of tramadol or placebo before hysteroscopy and endometrial biopsy were performed . MAIN OUTCOME MEASURE(S ) Visual analogue scale of pain was measured both immediately after and 15 minutes after the procedure . Stress hormones ( ACTH , cortisol ) , blood pressure , and heart frequency were evaluated before , during , and 15 minutes after the procedure . RESULT ( S ) In the tramadol group , the visual analogue scale of pain was significantly lower than in the placebo group both immediately after the procedure and 15 minutes later . Basal levels of ACTH and cortisol did not differ between the groups . In both groups , the ACTH levels remained unchanged during the study , and the cortisol levels were higher 15 minutes after the procedure than before the procedure . Procedure time , heart frequency , blood pressure , and adverse effects did not differ between the groups . CONCLUSION ( S ) In parous women without uterine malformations , a treatment with tramadol before hysteroscopy and endometrial biopsy appears to be capable of reducing the pain and discomfort that are associated with this procedure OBJECTIVE The aim of this study was to compare traditional hysteroscopy with mini-hysteroscopy in terms of compliance , side effects and diagnostic efficacy . STUDY DESIGN We prospect ively considered 950 female c and i date s for an IVF programme . All women underwent outpatient hysteroscopy ; in 602 cases ( Group A ) a mini-hysteroscope was employed ; in 348 women ( Group B ) a 5-mm hysteroscope was adopted . RESULTS Cavity findings were similar in both groups . Endometrial polyps and uterine septum seem to be more frequent in our infertile patients than in the general population . No significant differences in terms of side effects were found between the groups . Mean visual analogue pain scale score was significantly lower in the patients of Group A than in those of Group B ( p<0.001 ) . CONCLUSIONS Office mini-hysteroscopy is a very effective diagnostic tool in an infertility work-up and is more widely accepted than traditional hysteroscopy . Routine use of the technique should be considered OBJECTIVE To compare the efficacy of two modalities of local anesthesia for diagnostic hysteroscopy in different steps of the procedure in terms of pain control and time required for the examination . STUDY DESIGN One hundred eighty women undergoing diagnostic hysteroscopy were included in the study and r and omly allocated to one of two groups . Group A ( n = 88 ) , treated with prilocaine plus lidocaine cream , and group B ( n = 92 ) , treated with lidocaine spray , were compared with group C , a control group ( n = 165 ) , including all the hysteroscopies performed without anesthesia in the same period . Duration of the hysteroscopic examination was recorded ; intensity of pain induced by the procedure and shoulder pain 10 minutes after the end of the examination were recorded for all patients on the basis of a four-point pain scale . RESULTS Duration of the procedure required was two minutes in a significantly lower percentage of patients in group A as compared to groups B and C. Furthermore , in group A we found a significant reduction in pain at placement of the tenaculum in comparison to groups B and C. In groups A and B , no patient experienced a " very painful " grade of pain versus 4.8 % in group C. The vasovagal reaction rate was also significantly lower in both treated groups in comparison to the control group . Furthermore , the intensity of shoulder pain was significantly lower in the group receiving prilocaine plus lidocaine cream as compared to the other two groups . CONCLUSION Local anesthesia has a beneficial effect , at least in those hysteroscopies presumed to be , for whatever reasons , more cumbersome to perform . Prilocaine plus lidocaine cream was more effective than lidocaine spray in decreasing pain at placement of the tenaculum and shoulder pain after the procedure BACKGROUND Diagnostic hysteroscopy is not widely performed in the office setting , one of the reasons being the discomfort produced by the procedure . This r and omized controlled trial was performed to evaluate the effects of instrument diameter , patient parity and surgeon experience on the pain suffered and success rate of the procedure . METHODS Patients were r and omly assigned to undergo office diagnostic hysteroscopy either with 5.0 mm conventional instruments ( n=240 ) or with 3.5 mm mini-instruments ( n=240 ) . Procedures were stratified according to patient parity and surgeon 's previous experience . The pain experienced during the procedure ( 0 - 10 ) , the quality of visualization of the uterine cavity ( 0 - 3 ) and the complications were recorded . The examination was considered successful when the pain score was < 4 , visualization score was > 1 and no complication occurred . RESULTS Less pain , better visualization and higher success rates were observed with mini-hysteroscopy ( P < 0.0001 , P < 0.0001 and P < 0.0001 , respectively ) , in patients with vaginal deliveries ( P < 0.0001 , P < 0.0001 and P < 0.0001 , respectively ) and in procedures performed by experienced surgeons ( P=0.02 , P = NS and P = NS , respectively ) . The effects of patient parity and surgeon experience were no longer important when mini-hysteroscopy was used . CONCLUSIONS Our data demonstrate the advantages of mini-hysteroscopy and the importance of patient parity and surgeon experience , suggesting that mini-hysteroscopy should always be used , especially for inexperienced surgeons and when difficult access to the uterine cavity is anticipated . They indicate that mini-hysteroscopy can be offered as a first line office diagnostic procedure STUDY OBJECTIVE To assess acceptability and cardiovascular complications of hysteroscopy performed with minihysteroscopes compared with those performed with conventional hysteroscopes . DESIGN Prospect i ve , r and omized clinical trial ( Canadian Task Force classification I ) . SETTING Academic research center . PATIENTS One hundred women with abnormal uterine bleeding . INTERVENTIONS Hysteroscopy with a 3.5-mm minihysteroscope or conventional 5-mm endoscope with no anesthesia . MEASUREMENTS AND MAIN RESULTS Duration of examinations , pain , and occurrence of vasovagal reactions were recorded . Pain was assessed by visual analog scale ranging from zero to 20 before ( pain expectancy ) and at the end of the procedure . Occurrence of vasovagal reactions was assessed by monitoring blood pressure and pulse rate at 1-minute intervals during the procedure . A heart rate of less than 60/minute or a reduction greater than 20 % compared with baseline was considered a vasovagal reaction ; similarly , a reduction in blood pressure exceeding baseline value by 20 % was considered a result of vagal stimulation . Mean duration was shorter for minihysteroscopy than for conventional hysteroscopy . The mean ( SD ) level of pain experienced during minihysteroscopy also was significantly lower ( 0.76 + /- 0.65 vs 1.46 + /- 0.86 , 95 % CI-1.0 - 0.4 , p < 0.0001 ) . The number of instrumentally recorded ( 1 vs 11 cases ) and clinical vasovagal reactions ( 0 vs 6 cases ) was also significantly lower in the minihysteroscopy group than in the conventional hysteroscopy group ( p < 0.002 and < 0.02 , respectively ) . CONCLUSION New-generation minihysteroscopes make hysteroscopy easier and less painful , and carry a lower risk of vasovagal reactions than hysteroscopy performed with conventional instruments . In our experience , minihysteroscopy with vaginoscopic approach and saline distention is well tolerated , effective , and a true outpatient procedure Purpose Dilatation and curettage is frequently performed in gynecological practice . Aim of this prospect i ve r and omized double-blind placebo-controlled study was to evaluate the safety and efficacy of oral misoprostol to prime non-pregnant cervix before this procedure . Method Women requiring dilatation and curettage were included in the study . Exclusion criteria were visible growth in cervix or vagina , pregnancy , allergy to prostagl and ins , some medical disorders . Each participant was instructed to take either 400 µg of misoprostol or placebo orally 12 h before the procedure . Primary outcome measure was : diameter of the largest negotiable Hegar ’s dilator through internal os without any resistance at the beginning of the procedure . Secondary outcome measures were : percentage of women with initial cervical dilatation of ≥5 mm , time required for optimum cervical dilatation , percentage of failed procedures and complications . t test , Chi-square test and Fisher ’s test were used to compare the variables . Result Misoprostol significantly increased baseline cervical diameter in the pre-menopausal group ( p < 0.001 ) , but not in post-menopausal subjects ( p = 0.1 ) and reduced time required for cervical dilatation in both pre- and post-menopausal women . The number of patients achieving initial cervical dilatation ≥5 mm was significantly greater in pre-menopausal subjects receiving misoprostol , but not significant in post-menopausal ones . The drug was also found to be effective in both nulliparous and multiparous patients . Side effects were comparable between two groups . Only nausea and vomiting were more frequent in post-menopausal misoprostol group than placebo ( p = 0.018 ) . Conclusion Four hundred micrograms of oral misoprostol 12 h prior to dilation and curettage was found to be beneficial in cervical priming in pre-menopausal subjects . It was also found to be effective irrespective of the parity of the patients OBJECTIVE : To compare a “ no touch ” approach to diagnostic hysteroscopy without anesthesia with traditional diagnostic hysteroscopy after intracervical injection of mepivacaine hydrochloride 3 % . METHODS : A total of 130 women undergoing diagnostic hysteroscopy were included in the study and were r and omized , using a computer-generated r and omization list to one of two treatment groups in a ratio of 2:1 . Eighty-three women underwent hysteroscopy without speculum , tenaculum , or anesthesia . Forty-seven women received intracervical anesthesia with 10 mL of 3 % mepivacaine hydrochloride solution injected at two sites ( 3:00 and 9:00 positions ) and underwent traditional hysteroscopy . Hysteroscopy was performed using a rigid 3.7-mm hysteroscope and a medium of 0.9 % saline , and the image was transmitted to a screen visible to the patient . A visual analog scale ( VAS ) consisting of a 10-cm line was used to assess the intensity of pain experienced during and after the procedure . Overall patient satisfaction was assessed during , immediately after , 15 minutes later , and 3 days after hysteroscopy . RESULTS : The mean pain score was significantly lower in the group without the use of speculum , tenaculum , or anesthesia ( VAS1 : 3.8±2.7 versus 5.34±3.23 , P=.01 ; VAS2 : 3.02±2.50 versus 4.57±3.30 , P=.008 ) . Patient satisfaction rate was similar in both groups . CONCLUSION : Patients reported significantly less pain with the altered approach to diagnostic hysteroscopy compared with patients undergoing the traditional procedure with anesthesia . This new approach can therefore be considered as a useful hysteroscopic technique . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00319410 LEVEL OF EVIDENCE : PURPOSE to compare the pain reported by patients su bmi tted to hysteroscopy by the st and ard technique with carbon dioxide ( CO2 ) and to vaginal hysteroscopy with physiological saline ( 0.9 % NaCl ) . METHODS this was a prospect i ve cohort study conducted at an ambulatory hysteroscopy service . A total of 117 patients with indication for the exam were included , being r and omly assigned to one of the groups . All patients answered an epidemiological question naire and scored the pain expected before the exam and that felt after the end of the procedure on a verbal pain scale from 0 to 10 . A speculum , traction of the cervix , insertion of a 30 masculine light source and a diagnostic shirt with a total diameter of 5 mm were used for the st and ard technique . The cavity was distended with CO2 under a pressure of 100 mmHg controlled with a hysteroflator , and a biopsy was obtained with a Novak curette . Vaginoscopy was performed without a touch by distention of the vagina with fluid , direct visualization of the cervix and introduction of the light source with two continuous-flow shirts , with an accessory channel with an oval profile , the whole set measuring 5 mm in diameter . The medium distention was 0.9 % NaCl and the pressure used was that considered to be necessary for an adequate visualization of the canal and of the cavity with an external pneumatic pressurizer . The biopsy was obtained in a directed manner using an endoscopic clamp . The mean and st and ard deviation were calculated for the quantitative variables and the frequency was calculated for the qualitative variables . The Student 's t-test was used to compare the means , and the chi-square or exact Fisher test was used ( when n<5 ) for the categorical analysis using the SPSS 15.0 software . The study was design ed for a 95 % test power , with the level of significance set at p<0.05 . RESULTS the groups were similar regarding age , parity , previous uterine surgeries , menopausal status , and the need for a biopsy . In comparison to the group su bmi tted to the st and ard technique , the vaginoscopy group involved a lower technical difficulty ( 5.1 versus 17.2 % , p=0.03 ) , a higher rate of exams considered to be satisfactory ( 98.3 versus 89.7 % , p=0.04 ) and a lower pain index ( 4.8 versus 6.1 ; p=0.01 ) , as the difference were more evident when patients who never had a previous normal delivery were compared ( 4.9 versus 7.1 ; p=0.0001 ) . When the pain scale was stratified as mild ( 0 - 4 ) , moderate ( 5 - 7 ) or intense ( 8 - 10 ) , the vaginoscopy technique was found to be associated with a 52 % reduction of the frequency of intense pain ( p=0.005 ) . CONCLUSIONS vaginohysteroscopy was proved to be a less painful procedure than the technique based on the use of a speculum and CO2 , regardless of age , menopause or parity , with more satisfactory results and lower technical difficulty STUDY OBJECTIVE To assess the efficacy of sublingual buprenorphine in the relief of pain associated with office hysteroscopy . DESIGN Prospect i ve , r and omized study ( Canadian Task Force classification I ) . SETTING Tertiary medical center . PATIENTS One hundred sixty-four women referred for office hysteroscopy from September 2003 through March 2004 . INTERVENTION Before hysteroscopy , 80 women received a tablet of buprenorphine ( group A ) , and 84 women received a placebo ( group B ) . Their pain sensations were evaluated on a 10-cm visual analog scale , and they were asked about the adverse reactions and level of satisfaction on the following day . MEASUREMENTS AND MAIN RESULTS The pain score in group A was 3.3 + /- 1.1 , which was similar to 3.2 + /- 1.3 in group B. The pain scores in subgroups of women also were similar within the same group and between the two groups . Thirty-one women ( 38.8 % ) in group A reported adverse reactions , including nausea , vomiting , and drowsiness , while none in group B reported any adverse reactions . CONCLUSION Office hysteroscopy with a 3.1-mm flexible hysteroscope is a well-tolerated procedure . Sublingual buprenorphine is not helpful in relieving the pain associated with hysteroscopy but is associated with significant adverse reactions BACKGROUND A r and omized , controlled study was performed to compare vaginoscopic versus traditional ( speculum with or without tenaculum ) hysteroscopy in terms of pain score and procedure time . METHODS Three hundred patients were r and omized in two groups : Group A , diagnostic hysteroscopy with vaginoscopic approach ( 150 patients ) and Group B , diagnostic hysteroscopy with traditional approach ( 150 patients ) . All procedures were performed using a semi-rigid 3.5-mm minihysteroscope with a 0 degrees grade optic . Patients of each group were divided into three subgroups according to their reproductive status : fertile nulliparous ( FN ) , fertile multiparous ( FM ) and post-menopausal ( MEN ) women . Women were asked to rate their degree of pain during four phases of the procedure : introduction of hysteroscope ( Group A ) or speculum ( Group B ) into the vagina ( Phase I ) and progression through cervical canal up to internal uterine orifice ( IUO ) ( Phase II ) , inspection of uterine cavity ( Phase III ) and performing of endometrial biopsy ( Phase IV ) . A total pain score was calculated for each group . For each patient , the duration of hysteroscopy was recorded from the introduction to the extraction of the scope ( Group A ) or of the speculum ( Group B ) . RESULTS Although the median total pain scores were 2 in each group , the 95 % confidence interval for vaginoscopic hysteroscopy ( 1.86 - 2.01 ) was significantly ( P < 0.05 ) lower than that for traditional hysteroscopy ( 2.10 - 2.26 ) . Comparison between the corresponding phases of the procedure showed the only significant difference during Phase I of the procedure [ Group A : 1 ( 95 % CI 1.0 - 1.18 ) versus Group B : 2 ( 95 % CI 2.3 - 2.8 ) ; P < 0.05 ] . No significant differences in terms of duration of the procedure were observed between the two approaches . CONCLUSIONS When surgeons using vaginoscopic hysteroscopy with a semi-rigid minihysteroscope were compared with those using traditional approach and the same instrumentation , the operating times and the patients ' pain scores were similar Purpose The purpose of the study was to examine the feasibility of office hysteroscopy through the no-touch “ see and treat technique ” in a routine basis in private practice . Methods In the private practice of two trained gynecologists , women with an indication for further investigation of the uterine cavity were treated with the technique . A total of 112 consecutive women were prospect ively allocated to a “ no-touch ” and “ see and treat ” technique of hysteroscopy . Neither anaesthesia nor analgesia was used as soon as criteria were met . Hysteroscopy was performed using a rigid 3.4-mm hysteroscope and a medium of 0.9 % saline . Results Treatment efficacy and patient compliance were evaluated through scores on a visual analogue scale ( VAS ) for pain , complications and success rates , along with the symphony between hysteroscopic findings and histology . The patients ’ pain score on the VAS was low and only in 2 out of 112 cases there was a marked discomfort . In four cases suggested treatment was not successful , because of the fear of the patient . In 60.71 % of cases that hysteroscopy was indicated , the uterine cavity was normal . No complications or adverse effects were noted . Apart from one case , there was a full agreement between hysteroscopic findings and histology . Conclusion Office hysteroscopy is a successful and well-tolerated procedure . Through adequate expertise it should be considered the method of choice in private basis , at the same time when exploration of the uterine cavity is needed STUDY OBJECTIVE To identify predictors of unacceptable pain during office hysteroscopy without anesthesia . DESIGN Prospect i ve observational study ( Canadian Task Force classification II-2 ) . SETTING Teaching hospital . PATIENTS Five hundred fifty-eight women aged 17 to 73 years . INTERVENTION Elective office hysteroscopy without anesthesia . MEASUREMENTS AND MAIN RESULTS Pain intensity was assessed via a verbal rating scale ( VRS , 0 - 10 ) . Pain was considered unacceptable when severe during the procedure ( VRS ≥7 ) or moderate to severe at discharge ( VRS ≥4 ) . After preliminary statistical analysis , factors including diabetes , age ≤50 years , previous curettage , dyspareunia , severe dysmenorrhea , and hysteroscopist experience were selected to compose 2 binary multivariate models to predict unacceptable pain . As expected , hysteroscopist experience was protective against unacceptable pain during office hysteroscopy ( p = .03 ; adjusted odds ratio [ OR ] , 0.63 ; 95 % confidence interval [ CI ] , 41 - 96 ) and also at discharge ( p = .002 ; adjusted OR , 0.48 ; 95 % CI , 30 - 77 ) . Severe dysmenorrhea was a significant risk factor for pain ( cramps ) at discharge ( p < .001 ; adjusted OR , 3.07 ; 95 % CI , 1.97 - 4.78 ) . CONCLUSION Women with severe dysmenorrhea will benefit from preemptive analgesia regardless of hysteroscopist level of experience because this condition significantly increased the occurrence of unacceptable cramps at discharge STUDY OBJECTIVE To evaluate the amount of pain during office hysteroscopy and endometrial biopsy with and without intrauterine anesthesia . DESIGN Prospect i ve r and omized study ( Canadian Task Force classification I ) . SETTING Academic teaching center . PATIENTS A total of 82 women underwent outpatient hysteroscopy for evaluation of their uterine cavity . INTERVENTIONS R and omization to local cervical or combined cervical and intrauterine anesthesia . MEASUREMENTS AND MAIN RESULTS Amount of pain experienced during the procedure ; 10 , 30 , and 60 minutes after the procedure ; and during endometrial biopsy . We used a visual analog scale ranging from 0 to 10 ( 0 : no pain , 10 : excruciating pain ) . Of 82 patients , 4 patients were excluded , 36 patients underwent hysteroscopy using local cervical anesthesia , and 42 others with combined cervical and intrauterine anesthesia . The mean age of the patients in the local group was 37.4 + /- 0.8 years and in the combined group was 38.3 + /- 0.7 years . In both groups , patients experienced significantly more pain during and 10 minutes after the procedure than 30 and 60 minutes after . No significant differences occurred in the pain scores during the hysteroscopy , and 10 , 30 , and 60 minutes after between the 2 anesthesia groups . The pain score in the local group during endometrial biopsy was significantly higher than during ( p < .05 ) , 10 minutes after ( p < .001 ) , 30 minutes after ( p < .001 ) , and 60 minutes after ( p < .001 ) the procedure , respectively . In the combined group , compared with the pain score during endometrial biopsy , the scores during the hysteroscopy ( p < .05 ) , 10 minutes after ( p < .01 ) , 30 minutes after ( p < .001 ) , and 60 minutes after ( p < .001 ) the procedure were also less , respectively . CONCLUSION Intrauterine anesthesia with medicated saline as a distending medium is ineffective . Endometrial biopsy is associated with more pain than hysteroscopy Purpose To evaluate the efficacy of two routes of misoprostol ( sublingual and vaginal ) for cervical ripening before hysteroscopy . Methods One hundred and ten perimenopausal women who were referred to a tertiary hospital for surgical hysteroscopy enrolled in this double-blind r and omized clinical trial . They were divided into two groups to receive 400 mg misoprostol either sublingually or vaginally 6 h before hysteroscopy . The duration of dilatation , Hegar number inserted into the cervix without resistance , and hysteroscopic and drug complications were recorded for all cases . Results Forty-nine women in sublingual and 51 in vaginal group participated in the study . Dilatation time was significantly lower in sublingual group ( P < 0.001 ) . Median Hegar number passed into the cervix without resistance was 5 in sublingual versus 4 in vaginal group ( P = 0.002 ) . Cramp followed by vomiting and diarrhea were the most common side effects of misoprostol in the sublingual group , while cramp followed by vomiting was the most frequent side effect in the vaginal group . Diarrhea was not reported in the vaginal group ( P = 0.008 ) . ConclusionS ublingual route of misoprostol could be considered as an effective medication before surgical hysteroscopy in perimenopausal women STUDY OBJECTIVE To evaluate the specificity of blind biopsy in detecting benign intracavitary lesions as causes of postmenopausal bleeding in comparison with directed biopsy via hysteroscopy . DESIGN Prospect i ve trial without r and omization ( Canadian Task Force classification II-1 ) . SETTING University hospital . PATIENTS Three hundred nineteen postmenopausal women with abnormal uterine bleeding . INTERVENTIONS All patients underwent both blind biopsy ( Novak 's curette ) and directed biopsy via hysteroscopy ( after at least a week ) . All patients with benign intracavitary lesions underwent operative hysteroscopy to enable the removal of polyps and intracavitary myomas or endometrial resection if required . All patients with pathologic reports of complex hyperplasia and atypical hyperplasia ( 20 patients ) underwent vaginal hysterectomy with bilateral adnexectomy . All patients with histology reports of endometrial carcinoma ( 15 patients ) underwent abdominal hysterectomy , bilateral adnexectomy , and pelvic lymphadenectomy . Histopathologic findings from endometrial specimens obtained after operative hysteroscopy or uterine specimens obtained after hysterectomy were used as a reference test to establish the prevalence of disease . MEASUREMENTS AND MAIN RESULTS The sensitivity , specificity , accuracy , and positive and negative predictive values of blind biopsy and hysteroscopy were assessed to distinguish benign intracavitary formations such as polyps , submucous myomas , and endometrial hyperplasia in postmenopausal patients with abnormal uterine bleeding . The level of agreement was evaluated by use of the coefficient of concordance kappa . Blind biopsy showed a sensitivity of 11 % and a specificity of 93 % , with an accuracy of 59 % in detecting endometrial polyps , a sensitivity and specificity of 13 % and 100 % , respectively , with an accuracy of 98 % for submucous myomas , and values of 25 % , 92 % , and 80 % , respectively , in diagnosing hyperplasia . On the other h and , hysteroscopy demonstrated a sensitivity of 100 % and a specificity of 97 % , with an accuracy of 91 % in diagnosing endometrial polyps , a sensitivity and specificity of 100 % and 98 % , respectively , with an accuracy of 99 % for submucous myomas . The coefficient of concordance kappa ( 95 % CI ) was 0.12 for blind biopsy and 0.82 for hysteroscopy , corresponding , respectively , to slight concordance and almost perfect agreement with final pathologic diagnosis . CONCLUSIONS Blind biopsy ( Novak 's curette ) demonstrates very low sensitivity and accuracy in the diagnosis of benign focal intracavitary lesions . Hysteroscopy is confirmed as the gold st and ard in the assessment of abnormal uterine bleeding in menopause , permitting the elimination of the false-negative results of blind biopsy through direct visualization of the uterine cavity and the performance of targeted biopsy in case of doubt The visual analog scale ( VAS ) is one of the most commonly used measures of pain intensity in pain research . However , there remain important unanswered questions concerning interpretation of specific VAS ratings and change scores . To address these questions , we performed a re analysis of data from 2 r and omized controlled trials of postoperative pain ( N = 123 and N = 125 ) to determine the meaning of VAS pain intensity ratings and change scores . The findings suggested that 100-mm VAS ratings of 0 to 4 mm can be considered no pain ; 5 to 44 mm , mild pain ; 45 to 74 mm , moderate pain ; and 75 to 100 mm , severe pain . As predicted , in assessment of the amount of change corresponding to differing levels of pain relief , percentage change in a patient 's VAS score was less biased by pretreatment pain than was absolute change score . The findings also suggested that a 33 % decrease in pain represents a reasonable st and ard for determining that a change in pain is meaningful from the patient 's perspective STUDY OBJECTIVE To assess the roles of instrument diameter ( 5.0- or 3.5-mm external sheath ) , uterine distention medium ( carbon dioxide [ CO(2 ) ] or saline solution ) , and hysteroscopist experience in diagnostic hysteroscopy . DESIGN Prospect i ve , r and omized , multicenter trial ( Canadian Task Force classification I ) . SETTING Two university medical centers in Italy . PATIENTS One hundred eighty-four women attending an infertility clinic . INTERVENTIONS Patients were r and omly assigned to undergo conventional hysteroscopy ( group 1 , n = 92 ) or minihysteroscopy ( group 2 , n = 92 ) with CO(2 ) or saline solution as distention medium . The procedures were performed by hysteroscopists with varying degrees of experience . Patient discomfort was analyzed using the visual analog score . Procedure complications and patient satisfaction rate were also recorded . MEASUREMENTS AND MAIN RESULTS Independent of hysteroscopist experience , less pain , fewer complications , and higher satisfaction rates were observed with minihysteroscopy . In addition , procedures in which saline solution was used result ed in less pain and fewer complications than those in which CO(2 ) was used , but only when performed by inexperienced hysteroscopists . CONCLUSION Instrument diameter and hysteroscopist experience , but not the distention medium , seem to be the primary variables that affect the perception of discomfort during office hysteroscopy STUDY OBJECTIVE Fluid minihysteroscopy is in most cases a painless procedure . However , rarely , severe pain and side effects are reported . The goal of this study was to identify predictive factors of pain at minihysteroscopy . DESIGN Prospect i ve study ( Canadian Task Force classification II-2 ) . SETTING Academic environment . PATIENTS Five hundred thirty-three women undergoing fluid minihysteroscopy . INTERVENTIONS Diagnostic fluid minihysteroscopy . MEASUREMENTS AND MAIN RESULTS The women were asked to score pain perception on a visual analog scale from zero ( no pain ) to 5 ( unbearable pain ) . Correlation between pain at procedure and parity , previous cesarean section ( PCS ) , menopausal status , anxiety , and chronic pelvic pain ( CPP ) was evaluated . Four hundred thirteen women ( 78 % ) reported no pain or discomfort ( 0 - 1 pain score , group A ) , while 120 ( 22 % ) experienced mild to unbearable pain ( 2 - 5 pain score , group B ) . Instances of PCS , CPP , anxiety , and menopause were significantly lower in group A than in group B ( 4 % vs 82 % , 0 % vs 29 % , 62 % vs 72 % , 25 % vs 72 % , respectively ) , whereas menopausal status was less frequent in group A ( 25.2 % ) than in group B ( 72.5 % ) . At binary logistic regression , all the variables were independent risk factors for pain ; however , when CPP was stratified for intensity , no correlation between pain at procedure and intensity of CPP was found . CONCLUSION Previous cesarean section , CPP , anxiety , and menopause are predictive factors for pain perception during fluid minihysteroscopy , and history of CPP even of low intensity is predictive of pain at hysteroscopy . These patients may benefit from local anesthesia Purpose We investigated the feasibility and acceptability of office hysteroscopic polypectomy using a new continuous-flow operative 16 Fr Gubbini ’s mini-resectoscope . This is a prospect i ve clinical study ( Canadian Task Force classification III ) . Methods The office hysteroscopic polypectomy was performed with a mini-resectoscope without analgesia or anesthesia . We evaluated the polyp size and the number , the effectiveness of resection , the operating time , the pelvic pain and complications . Results The office hysteroscopic polypectomy was successfully performed in all 33 patients . The polyps ranged in size from 5 to 50 mm with a mean of 18.15 ± 11.45 mm . We analyzed the operating time with a mean of 11.45 ± 4.71 min : 29 procedures took less than 15 min from the start of vaginoscopy to the end of surgery . Overall mean visual analog scale ( VAS ) calculated was 2.48 ± 1.37 ( range 0–6 ) . The correlation between the size of the polyps and operating time was statistically significant ( p < 0.001 ) . No major complications were recorded . Conclusion Our preliminary data demonstrated that can be possible to remove endometrial polyps by hysteroscopy , using the mini-resectoscope , in an office setting . All procedures were completed successfully and well tolerated with a little discomfort permitting the removal also of big sized polyps without a statistical correlation between VAS and size of polyps or operating time . The outpatient polypectomy is a less-costing procedure and represents an acceptable and effective alternative to inpatient resectoscopic polypectomy , leading to a complete polyp excision in nearly all patients OBJECTIVE To compare 2.7- and 4-mm rigid optics , with 3- and 5-mm outer sheaths , respectively , in office diagnostic hysteroscopy by evaluating pain , patient tolerability , optical view and diagnostic accuracy of the procedure . STUDY DESIGN Three hundred seventy-one consecutive patients undergoing hysteroscopy were included in a prospect i ve , r and omized clinical trial , and the outcomes were analyzed . A saline solution was used as the distension medium . The t test for unpaired sample s , chi2 tables of contingency and ANOVA 2 x 3 were used where appropriate . The study took place at Tor Vergata University Hospital of Rome , Rome , Italy . The 371 women were referred consecutively for suspected endometrial pathologies and were separated into 2 groups . Diagnostic accuracy of the hysteroscopic procedure , pain experienced by the 2 groups ( as assessed by a visual analogue score ) and patient acceptability were assessed with a question naire . RESULTS Satisfactory hysteroscopy was achieved in 253 of 310 patients with a 2.7-mm hysteroscope and in 47 of 61 patients with a 4-mm hysteroscope . This difference was not significant . Menopausal status was the most important factor influencing the practicability of the hysteroscopic procedure ( p < 0.001 ) . CONCLUSION The narrower-diameter hysteroscopes tended to lower the incidence of pain associated with office hysteroscopy , but this was not significant . Parity did not show any influence on hysteroscopic practicability . Menopausal status was the most important factor influencing the feasibility of the hysteroscopic procedure STUDY OBJECTIVE To evaluate influence of hysteroscope type and media used during outpatient hysteroscopy on vasovagal syndrome risk . STUDY DESIGN Prospect i ve observational study ( Canadian Task Force classification II-1 ) . SETTING University hospital . PATIENTS Two thous and seventy-nine women undergoing outpatient hysteroscopy without analgesia . INTERVENTION Office hysteroscopy with a flexible or rigid hysteroscope and normal saline or CO(2 ) . MEASUREMENTS AND MAIN RESULTS Fifteen cases of vasovagal syndrome were reported . The rate of vasovagal syndrome was higher with use of a rigid hysteroscope ( 12/647 [ 1.85 % ] ) vs. a flexible hysteroscope ( 3/1432 [ 0.21 % ] ) , p = .00013 ; p = .009 after adjustment for medium used ; and with the use of CO2 ( 10/426 [ 2.34 % ] ) vs. saline solution ( 5/1653 [ 0.30 % ] ) , p < .0001 ; p = .014 after adjustment for hysteroscope type . CONCLUSION Risk of vasovagal syndrome is higher with the use of a rigid hysteroscope and CO2 , regardless of the indication for hysteroscopy or the parity and menopausal status of the patient STUDY OBJECTIVE To investigate the pain and acceptability of diagnostic hysteroscopy performed without local anesthesia . DESIGN Prospect i ve , observational study ( Canadian Task Force classification II-2 ) . SETTING University-associated department of obstetrics and gynecology . PATIENTS The 1144 consecutive women who underwent diagnostic hysteroscopy . INTERVENTIONS Diagnostic hysteroscopy and endometrial biopsy as indicated . MEASUREMENTS AND MAIN RESULTS Patients were asked to rate the pain experienced on a 10-cm visual analog scale and to state if they were willing to repeat the procedure . The mean pain score was 4.7 + /- 2.5 ; 398 patients ( 34.8 % ) experienced severe pain . No risk factors for painful hysteroscopy were found , although abnormality of the cervical canal was associated with high pain scores . Acceptance of the procedure was high , 83.0 % ( 950 women ) . CONCLUSION Diagnostic hysteroscopy is a painful procedure even when performed with atraumatic technique by experienced surgeons . Most women , however , stated they were willing to have a second procedure under the same conditions OBJECTIVE To evaluate the effectiveness of transcutaneous electrical nerve stimulation ( TENS ) as a pain control method during office hysteroscopy . DESIGN A prospect i ve , r and omized study . SETTING Centre for Minimally Invasive Surgery , Department of Gynecological Science and Perinatology , " La Sapienza " University , Rome , Italy . PATIENT(S ) One hundred forty-two patients undergoing office hysteroscopy . INTERVENTION(S ) Application of a TENS device on the patient 's abdomen before and during office hysteroscopy . MAIN OUTCOME MEASURES The level of pain experienced by the patients was assessed using a 10 cm visual analog scale ; the side effects and changes in the hemodynamic parameters were evaluated . RESULT ( S ) The patients treated with TENS during hysteroscopy ( group A , n = 71 ) were compared with a control group ( group B , n = 71 ) on whom the TENS device was not used . The women in the TENS group experienced a significantly lower level of pain during hysteroscopy . No differences in side effects were observed between both group . CONCLUSION ( S ) TENS is a simple , efficient , and safe method of relieve pain during office hysteroscopy Objective To assess the efficacy of lidocaine spray during outpatient hysteroscopy for reducing procedure-related pain and to identify risk factors for discomfort . Methods One hundred twenty-one women were assigned r and omly to have application of lidocaine spray or placebo to the uterine cervix during outpatient hysteroscopy . The main outcome measure was pain during hysteroscopy , assessed on a visual analog scale . Results There was no statistically significant difference between study and control groups in mean age , rate of nulliparity , postmenopausal state , need for cervical dilation , or percentage of women who used hormone replacement therapy . Indications for diagnostic hysteroscopy were similar between groups . Women in the lidocaine group had statistically significantly less pain during the procedure than women in the placebo group ( 2.2 ± 1.9 and 3.7 ± 2.5 , respectively ; P < .001 ) . Women with abnormal uterine findings ( submucous myoma , endometrial polyps , or intrauterine adhesions ) had significantly higher pain scores than women with normal cavities ( 2.2 ± 1.9 and 3.2 ± 2.4 , respectively ; P < .002 ) . Aerosol anesthesia and normal uterine findings were independently associated with less pain . No procedure had to be ab and oned because of excessive pain or complications , and no women required hospitalization . Conclusion Women treated with lidocaine spray had significantly less pain . Uterine cavity abnormality might be associated with a higher degree of pain during hysteroscopy Background . Three methods of diagnostic hysteroscopy have been tested for both women 's compliance and feasibility of procedures in postmenopause To evaluate patient acceptance , optical properties and the clinical feasibility of flexible compared with rigid hysteroscopes , 142 patients undergoing outpatient hysteroscopy were included in a prospect i ve , r and omized clinical trial . The flexible hysteroscope was used in 70 patients , and the rigid instrument in 72 . At different stages of the hysteroscopy the level of pain experienced by the women was assessed using a 10 cm visual analogue scale . Optical properties characterized by the parameters intrauterine visibility , hysteroscopic view and diagnostic accuracy were ranked by the surgeons using a 5-point scale ( 1 = excellent to 5 = insufficient ) , and duration of the hysteroscopy was measured . Hysteroscopy was successful in 87.5 and 100 % of patients in the flexible and rigid groups respectively . With the use of rigid telescopes , discomfort at introduction and during the hysteroscopy was significantly greater ( median 1.7 versus 0.7 , P = 0.003 ; 3.1 versus 1.2 , P < 0.001 respectively ) , but optical properties were judged to be far superior ( P < 0.001 for all three comparisons ) and procedure time was significantly shorter ( median 70 versus 120 s , P = 0.003 ) . In conclusion , outpatient hysteroscopy seems to be less painful when using flexible telescopes . However , rigid hysteroscopes provide superior optical qualities and permit a more rapid performance with higher success rates at much lower cost BACKGROUND Diagnostic hysteroscopy has not yet been generally accepted as a well-tolerated office procedure . The aim of our study was to verify compliance , side-effects and haemodynamic variations when a mini-hysteroscope is used . METHODS A prospect i ve r and omized trial on office hysteroscopy was performed by comparing the use of a traditional 5 mm hysteroscope ( group A ) and of a 3.3 mm mini-hysteroscope ( group B ) . Two patient groups ( A and B ) , each comprising 100 cases , were formed on the basis of a r and omized computer-generated list . RESULTS A marked reduction in the mean ( + /- SD ) pelvic pain score during office hysteroscopy was seen in group B ( 2.3 + /- 2.1 ) as compared with group A ( 4.6 + /- 2.2 ) ( P < 0.0001 , Mann-Whitney test ) . This result was also confirmed when using an alternative approach : four classes of pelvic pain at the visual analogue score ( VAS ) . A significant reduction was observed in the incidence of moderate and severe pelvic pain in group B at the end of the examination ( P = 0.001 ) and 5 - 10 min later ( P < 0.05 ) . CONCLUSIONS The use of mini-hysteroscopes ( 3.3 mm with diagnostic sheath ) lowers considerably the level of pelvic pain the patients feel : it is halved in comparison with traditional calibre hysteroscopes ( 2.3 + /- 2.1 , on a 0 - 10 VAS ) . Furthermore the outpatient hysteroscopy failure rate is less than half ( 2 % ) with the mini-hysteroscope compared with the traditional 5 mm hysteroscope ( 5 % ) . As for side-effects and haemodynamic parameters , no differences were observed except for an increase ( P < 0.05 ) in bradycardia in group B. The advantage of this technique is self-evident , if the patients ' compliance is taken into account : in many cases the introduction or withdrawal of the vaginal speculum was reported as the greatest discomfort STUDY OBJECTIVE To investigate the effects of music on anxiety and perception of pain during office hysteroscopy . DESIGN Prospect i ve r and omized trial ( Canadian Task Force classification I ) . SETTING Major university medical center . INTERVENTIONS Three hundred fifty-six patients were enrolled between July 2012 and January 2013 . Hysteroscopy was performed in a dedicated ambulatory room , using vaginoscopy and without any type of anesthesia . A Bettocchi hysteroscope 5 mm in diameter was used . All procedures were performed by the same surgeon , a gynecologist with special interest in hysteroscopy . MEASUREMENTS AND MAIN RESULTS Data collected included age , body mass index , number of vaginal deliveries , educational achievement level , and history of endometrial surgery ( curettage and /or hysteroscopy ) . For each patient , vital parameters such as blood pressure , heart rate , and respiratory rate were recorded 15 minutes before the procedure and during hysteroscopy after traversing the cervix . Wait time before surgery and the duration of the procedure were also recorded . A completed Italian version of the state anxiety question naire ( State-Trait Anxiety Inventory ) and a visual analog scale ( VAS ) were administered to each patient before and after the procedure . The t test and Mann-Whitney U test was used when appropriate to compare the 2 groups . Statistical significance was accepted at p = .05 . During surgery , systolic blood pressure and heart rate were significantly lower in the music group compared with the no music group . Women in the music group experienced significantly lower anxiety after hysteroscopy and less pain during the procedure , and a significant decrease in both anxiety and pain scores after hysteroscopy . Postoperative State-Trait Anxiety Inventory form Y1 and VAS scores were significantly lower in the music group . CONCLUSION Music can be useful as a complementary method to control anxiety and reduce perception of pain . The patient is more relaxed and experiences less discomfort |
1,614 | 26,888,026 | Currently available data from RCTs are sufficient to confirm that both lidocaine admixture and pretreatment were effective in reducing pain on propofol injection .
Furthermore , there were no significant differences of effect between the two techniques | BACKGROUND Pain on propofol injection is an untoward effect and this condition can reduce patient satisfaction .
Intravenous lidocaine injection has been commonly used to attenuate pain on propofol injection .
Although many studies have reported that lidocaine was effective in reducing the incidence and severity of pain , nevertheless , no systematic review focusing on lidocaine for preventing high-intensity pain has been published .
OBJECTIVES The objective of this review was to determine the efficacy and adverse effects of lidocaine in preventing high-intensity pain on propofol injection . | Background To analyze how lidocaine 40 mg mixed prevents injection pain of propofol affects the onset time of rocuronium , tracheal intubating conditions and intubation related hemodynamic changes . Methods This study consisted of 70 patients with an American Society of Anesthesiologists ( ASA ) physical status class 1 or 2 for general anesthesia . All the patients were r and omly allocated into two groups : propofol 2 mg/kg plus normal saline 2 ml ( Group C ) and propofol 2 mg/kg plus 2 % lidocaine 40 mg ( Group L ) . Each group was administrated intravenously during induction and the patient was intubated 1 minute after an injection of 0.6 mg/kg of rocuronium . The time at disappearance of the first twitch and intubation scores were recorded . Also , blood pressure and heart rate were measured at the baseline , after intravenous injection of propofol , before intubation , and at 0 , 1 , 2 , 3 and 5 minutes after intubation . Results There were no significant differences between group C and L ( P > 0.05 ) . Conclusions 40 mg of lidocaine mixed with propofol to prevent injection pain did not affect the onset time of rocuronium , intubating conditions and intubation related hemodynamic changes The aim of this study was to determine whether pretreatment with alkalinised lignocaine reduced the incidence and severity of pain during propofol injection . This prospect i ve , r and omised , double-blind study included 300 adult , American Society of Anesthesiologists physcial status I to II patients undergoing elective surgery . Patients were r and omly allocated to one of three groups : Group L received 0.05 ml/kg of 1 % lignocaine ( 5 ml normal saline + 5 ml 2 % lignocaine ) , Group A received 0.05 ml/kg alkalinised lignocaine ( 5 ml 2 % lignocaine + 1 ml 8.4 % NaHCO3 + 4 ml normal saline ) , and Group S , the control group , was given the same amount of normal saline ( NaCl 0.9 % ) . All drugs were given as a bolus over 20 seconds before propofol administration . A blinded research er assessed the patient 's pain level using a four-point scale . The pain score [ median ( range ) ] and the incidence of pain in Group A ( 6 % ) was significantly lower than in groups L ( 41 % ) and S ( 88 % , P < 0.001 ) . In addition , the pain score and the incidence of pain were found to be significantly different between Group L and Group S ( P < 0.001 ) . The incidence of moderate and severe pain were greater in Group S when compared with groups A and L ( P < 0.001 ) . Intravenous pretreatment with alkalinised lignocaine appears to be effective in reducing the pain during propofol injection Pain on injection , reported in 28 - 90 % of patients , is one of the most described side effects of the intravenous application of propofol . Many different approaches have been used in attempts to minimize propofol induced pain , with varied results . Using a r and omized , double-blind protocol design , the author-section pain following the administration of two different particle size formulations of propofol with or without lidocaine in 388 nonpremedicated ASA I-II adult patients scheduled for elective surgery under general anesthesia . Patients were allocated r and omly to receive either a small particle size lipid emulsion of propofol ( Anepol : average particle size 140.5 nm ) , or st and ard propofol ( Propofol : average particle size 193.3 nm ) , by dividing into 4 groups . Group 1 received 2 ml NaCl 0.9 % and Propofol , group 11 received 2 ml lidocaine 2 % and Propofol , group III received 2 ml NaCl 0.9 % and Anepol and group IV received 2 ml lidocaine 2 % and Anepol into a dorsal vein of the h and . Pain during propofol injection was evaluated over 5 - 10 seconds , until loss of conscious , using a four point scale . Sixty-seven patients ( 69.1 % ) complained of pain in group 1 , as compared with 50 % , 41.2 % and 39.2 % in group II , III and IV ( p < 0.05 ) . The reported severity of injection pain was not significantly different between the groups . The authors conclude that small particle size propofol causes less pain on injection than st and ard propofol BACKGROUND Propofol formulated with medium- and long-chain triglycerides ( MCT/LCT ) causes less pain on injection than st and ard Propofol , but the incidence of pain persists between 28 and 67 percent . Such a broad range begs the question so the authors wanted to clarify whether the addition of lidocaine to medium- and long-chain triglyceride emulsion propofol results in any clinical ly significant lessening of pain on injection . The authors conducted a r and omized , prospect i ve , double-blinded study to compare the injection pain felt following the administration of propofol-MCT/LCT ( Propofol-Lipuro ) to propofol-MCT/LCT plus 20 mg lidocaine for the induction of anesthesia . MATERIAL AND METHOD The present study included 270 non-premedicated ASA I-II adult patients scheduledfor elective surgery under general anesthesia . Patients were allocated r and omly into two groups to receive either propofol-MCT/LCT alone or propofol-MCT/LCT plus 20 mg lidocaine . The study solution was injected at 1 mL/second by one anesthesiologist and patients grade d any associated pain using a four-point scale . RESULTS The overall incidence of pain on injection was 31/133 ( 23 % ) in the propofol-MCT/LCT plus lidocaine group vs. 45/135 ( 33 % ) in the propofol-MCT/LCT alone group . The difference in the incidence of pain on injection between groups failed to achieve statistical significance ( p = 0.23 ) and no significant difference in intensity of pain between the two study groups occurred CONCLUSIONS The authors concluded that the addition of lidocaine ( 20 mg ) to the propofol-MCT/LCT does not significantly reduce the incidence or severity of the pain on injection BACKGROUND Propofol is commonly used for induction and maintenance of anesthesia , but pain at the site of intravenous injection is a clinical problem . We studied the effectiveness of local cooling and pretreatment with lidocaine for prevention of injection pain of propofol . METHODS A total of 226 adult patients scheduled to receive general anesthesia were assigned r and omly to four groups : a control group receiving no prophylactic intervention , a cooling group receiving topical cooling , a lidocaine group receiving 1 mg x kg(-1 ) lidocaine , and a lidocaine plus cooling group receiving topical cooling and 1 mg x kg(-1 ) lidocaine . A 20 gauge intravenous catheter was inserted into the peripheral vein at the radial side of the forearm . After prophylactic intervention had been performed , 1 - 2 mg x kg(-1 ) MCT/LCT propofol was injected . Patients were asked to grade the pain as none , mild , moderate , or severe . RESULTS The incidence of propofol-induced pain was significantly higher in the control group ( 39 % ) than in the other three groups ( 17 % in the cooling group , 16 % in the lidocaine group and 8 % in the lidocaine plus cooling group ) . However , there were no significant differences between the three groups with different prophylactic interventions . CONCLUSIONS The results suggest that cooling and pretreatment with lidocaine reduce the incidence of pain upon propofol injection BACKGROUND Pain on injection is a recognized adverse event ( AE ) with propofol , an agent used to induce general anesthesia in surgical patients . Lidocame ( LID ) has been found efficacious in reducing pain on injection of propofol ; however , this type of pain may not be completely eliminated with LID . Metoclopramide ( MET ) is a dopamine receptor agonist with antiemetic and prokinetic properties used for the treatment of nausea and facilitation of gastric emptying in patients with gastroparesis . MET also has local anesthetic properties similar to those of LID . OBJECTIVE The aim of this study was to examine the effects of LID administered with 3 different doses of MET or saline on pain on injection of propofol in Japanese adults undergoing elective surgery . METHODS This r and omized , double-blind study was conducted at the Department of Anesthesiology , University of Tsukuba Institute of Clinical Medicine , Tsukuba , Japan . Japanese patients aged 20 to 67 years who were scheduled to undergo elective surgery were eligible for participation . Patients were r and omized to receive N administration of LID 40 mg + MET 2.5 , 5 , or 10 mg or saline . A rubber tourniquet was used to perform 1 minute of venous occlusion before administration of the study and control drugs , and then 25 % of the total calculated dose of propofol ( 2 mg/kg ) was injected into the dorsal vein of the h and through a 20-G N cannula at a rate of 1 mL/s . During a 10-second pause before the induction of anesthesia , patients were question ed by a blinded investigator about the pain intensity on injection . Pain intensity was assessed through the use of a 4-point verbal rating scale , with scores ranging from 0 ( no pain ) to 3 ( severe pain ) . Incidence and intensity of pain ( as assessed by mean pain scores ) were determined in each of the 4 study groups . Extrapyramidal reactions and injection-site AEs , including pain , edema , wheals , and inflammation occurring up to 24 hours after surgery were recorded by a blinded investigator . RESULTS The study enrolled 240 patients ( 126 men , 114 women ; mean [ SD ] age , 43 [ 13 ] years [ range , 20 - 67 years ] ; mean [ SD ] height , 160 [ 8 ] cm [ 133 - 181 cm ] ; mean [ SD ] body weight , 57 [ 10 ] kg [ range , 33 - 85 kg ] ) . There were 60 patients r and omized to each of the 4 study groups , which were comparable in distribution of demographic characteristics . Incidence of propofol-induced pain was significantly lower , but the intensity of pain was not less , in the groups that received LID/MET 40/5 or 40/10 ( both , 5 % ) compared with those who received LID/MET 40/2.5 or LID/saline ( 18 % and 20 % , respectively ) ( all , P < 0.05 ) . There were no reports of injection-site AEs or extrapyramidal reactions after injection of the control or study drugs in any of the study groups . CONCLUSION Among these 240 Japanese patients undergoing elective surgery , N administration of LID/MET 40/5 or 40/10 was associated with lower incidence , but not lower mean pain intensity scores , of pain on injection of propofol than LID/MET 40/2.5 or LID/saline before induction of anesthesia A r and omised , double‐blind , controlled trial was undertaken to compare three different methods of reducing pain during the intravenous injection of propofol . In 101 patients undergoing daycase surgery , verbal rating scores , for pain during injection of propofol were compared immediately after intravenous pretreatment with ketorolac 10 mg , lignocaine 10 mg or saline . Neither pain during injection ( p = 0.129 ) , nor venous sequelae at 7 days postoperatively were significantly different between the three treatments . Pain during propofol injection remains a confounding clinical problem Background : Several commercial formulations of propofol are available . The primary outcome of this study was the required dose of propofol alone or combined with lidocaine to achieve induction of general anesthesia . Methods : This multicenter , double-blinded trial r and omized patients ( American Society of Anesthesiologists physical status I – III ) just before elective surgery with the use of a computer-generated list . Three different propofol 1 % formulations — Diprivan ® ( Astra-Zeneca , Cheshire , United Kingdom ) , Propofol ® ( Fresenius-Kabi AG , Bad Homburg , Germany ) , and Lipuro ® ( B-Braun , Melshungen AG , Germany)—were compared with either placebo ( saline solution ) or lidocaine 1 % mixed to the propofol solution . Depth of anesthesia was automatically guided by bispectral index and by a computerized closed-loop system for induction , thus avoiding dosing bias . The authors recorded the total dose of propofol and duration of induction and the patient ’s discomfort through a behavioral scale ( facial expression , verbal response , and arm withdrawal ) ranging from 0 to 6 . The authors further evaluated postoperative recall of pain using a Visual Analog Scale . Results : Of the 227 patients enrolled , 217 were available for analysis . Demographic characteristics were similar in each group . Propofol ® required a higher dose for induction ( 2.2 ± 0.1 mg/kg ) than Diprivan ® ( 1.8 ± 0.1 mg/kg ) or Lipuro ® ( 1.7 ± 0.1 mg/kg ; P = 0.02 ) . However , induction doses were similar when propofol formulations were mixed with lidocaine . Patient discomfort during injection was significantly reduced with lidocaine for every formulation : Diprivan ® ( 0.5 ± 0.3 vs. 2.3 ± 0.3 ) , Propofol ® ( 0.4 ± 0.3 vs. 2.4 ± 0.3 ) , and Lipuro ® ( 1.1 ± 0.3 vs. 1.4 ± 0.3 ) , all differences significant , with P < 0.0001 . No adverse effect was reported . Conclusion : Plain propofol formulations are not equipotent , but comparable doses were required when lidocaine was concomitantly administered Background Lidocaine has been used widely to prevent propofol injection pain . Various methods of administration exist , such as lidocaine premixed with propofol or lidocaine pretreatment using a tourniquet , but it is unclear which method of lidocaine administration is more effective for the prevention of injection pain of propofol LCT/MCT . The purpose of this study was to compare pretreatment of lidocaine with a tourniquet and a premixed injection of lidocaine to prevent injection pain of propofol-LCT/MCT . Methods Patients were r and omly allocated into the pretreatment group ( n = 117 ) or the premixed group ( n = 117 ) . The pretreatment group was pretreated with 2 ml of lidocaine 2 % , held with a tourniquet , before propofol-LCT/MCT injection . The premixed group was injected with a premixed solution of propofol-LCT/MCT and 2 ml of lidocaine 2 % . To evaluate the incidence and severity of pain , spontaneous verbal expressions of pain , movement of h and , frowning , and moaning were recorded , and the patients were asked to recall their pain with the visual analogue score ( VAS ) 30 minutes after awakening from anesthesia . Results Overall , injection pain occurred in 13.7 % of the pretreatment group and 15.4 % of the premixed group , without any statistical difference ( P = 0.71 ) . There was no difference in spontaneous verbal expressions of pain , movement of h and , frowning , and moaning between the two groups . The pain intensity ( VAS ) also showed no difference between the two groups ( P = 0.49 ) . Conclusions Pretreatment of lidocaine with a tourniquet showed no more benefit to prevent injection pain of propofol LCT/MCT compared to a premixed injection with lidocaine The purpose of this study was to define the optimum dose of lignocaine required to reduce pain on injection of propofol . We conducted a prospect i ve , r and omized , double-blind trial on 310 patients undergoing anaesthesia . Patients were allocated to four groups according to the lignocaine dosage : group A ( control ) , no lignocaine ; group B , lignocaine 0.1 mg kg-1 ; group C , lignocaine 0.2 mg kg-1 ; group D , lignocaine 0.4 mg kg-1 . Our results showed that a dose of lignocaine 0.1 mg kg-1 significantly reduced the incidence of pain and that there was no improvement when the dose was increased Background and objective : Propofol is associated with pain on injection . It is common practice to premix lidocaine with propofol prior to injection . Lipuro propofol , a propofol emulsified in medium‐ and long‐chain triglycerides , has been shown to reduce the intensity of injection pain compared to Diprivan ® , although a number of studies report no reduction in overall incidence of pain . Methods : We conducted this r and omized double‐blind trial to determine the extent of further pain reduction by adding lidocaine to Lipuro propofol . A total of 328 ASA I – III patients were r and omized to one of four groups to receive Diprivan propofol ( Group DP ) , Lipuro propofol ( Group LP ) , Diprivan with lidocaine ( Group DL ) and Lipuro propofol with lidocaine ( Group LL ) . The drug mixture was administered at a constant rate of 400 mL h−1 via a 20‐G cannula into a dorsal h and vein . Pain was assessed during induction and upon patient recovery , using a 10‐point visual analogue scale . Results : Both the incidence and severity of pain were found to be significantly lower with addition of lidocaine to Lipuro propofol ( P < 0.0002 ) compared to Lipuro alone , Diprivan with or without the addition of lidocaine . Conclusion : Lidocaine added to Lipuro propofol makes induction of anaesthesia less painful compared to Lipuro propofol alone or Diprivan with lidocaine BACKGROUND Pain on injection is a recognized adverse event ( AE ) of propofol administration for the induction of general anesthesia . Pretreatment with lidocaine , metoclopramide , or flurbiprofen axetil has been reported to be effective in reducing propofol-induced pain . However , no studies comparing the efficacy of these 3 drugs for preventing pain on injection of propofol have been identified . OBJECTIVE The aim of this study was to compare the efficacy of lidocaine , metoclopramide , and flurbiprofen axetil for reducing pain on injection of propofol in Japanese adult surgical patients . METHODS This prospect i ve , r and omized , double-blind , parallel-group , placebo-controlled study was conducted at the Department of Anesthesiology , Ushiku Aiwa General Hospital , Ibaraki , Japan . Japanese patients scheduled to undergo elective surgery were eligible for inclusion in the study . Patients were r and omized into 4 groups to receive IV lidocaine 40 mg , metoclopramide 10 mg , flurbiprofen axetil 50 mg , or placebo ( saline ) , preceded by venous occlusion with a rubber tourniquet for 2 minutes , and followed by the administration of propofol 0.5 mg/kg into the largest vein of the h and through a 20-gauge IV cannula . Immediately after the administration of propofol , an investigator blinded to treatment interviewed each patient on injection-site pain . Responses were scored on a 4-point verbal rating scale ( 0 = none , 1 = mild pain , 2 = moderate pain , and 3 = severe pain ) . Incidence and intensity of pain ( as assessed by mean pain scores ) were determined in each of the 4 study groups . AEs at the injection site ( eg , pain , edema , wheal , inflammation ) , extrapyramidal disturbance , and symptoms or signs associated with gastrointestinal ( GI ) ulceration were assessed by the study investigator for 24 hours following surgery using spontaneous reporting and patient interview . RESULTS A total of 100 patients ( 54 women , 46 men ) aged 22 to 65 years were enrolled in the study . The patients ' mean ( SD ) age was 42 ( 12 ) years . Their mean ( SD ) height was 161 ( 8) cm and their mean ( SD ) weight was 59 ( 9 ) kg . Each treatment group comprised 25 patients . There were no significant differences in demographic characteristics between treatment groups . The overall incidence of propofol-induced pain was 24 % ( 6/25 patients ) with lidocaine ( P = 0.001 ) , 28 % ( 7/25 patients ) with metoclopramide ( P = 0.001 ) , and 36 % ( 9/25 patients ) with flurbiprofen axetil ( P = 0.001 ) , compared with placebo ( 92 % , [ 23/25 patients ] ) . The median pain score was less in patients who had received lidocaine ( 0 ) , metoclopramide ( 0 ) , or flurbiprofen axetil ( 0 ) than in those who received placebo ( 2 ) ( all , P = 0.001 ) . The incidence and severity of such pain were not significantly different between the lidocaine- , metoclopramide- , and flurbiprofen axetil-treated groups . There were no reported injection-site AEs , extrapyramidal disturbance , or symptoms or signs associated with GI ulceration observed . CONCLUSIONS In this study of Japanese adult surgical patients , lidocaine 40 mg , metoclopramide 10 mg , and flurbiprofen axetil 50 mg , preceded by venous occlusion for 2 minutes , were effective in reducing pain during the injection of propofol . The analgesic efficacy of these 3 drugs was comparable for minimizing such pain Objectives : The aim of this study was to investigate the efficacy of dezocine ( DEZ ) versus placebo control ( CON ) and 2 % lidocaine ( LID ) in prevention of injection pain due to DEZ . Material s and Methods : A prospect i ve r and omized double-blind , placebo-CON study was conducted in 75 adults , American Society of Anesthesiologists physical status I or II , scheduled to undergo an elective surgery . A total of 25 patients were r and omly assigned to one of the three groups , thus CON , group LID and group DEZ . The groups received either 2 ml of normal saline or 2 ml 2 % LID or 2 mg/2 ml DEZ , respectively , as pre-treatment . Propofol was injected 1 min later . A blinded research er assessed the patient 's pain level using a four point verbal rating scale . Results : Less patients experienced pain due to propofol injection in the LID ( 40 % ) and DEZ ( 28 % ) groups compared with the CON ( 84 % ) group ( P < 0.05 ) . Six patients ( 24 % ) in the CON group reported severe pain during propofol injection but none in the other two groups . Conclusion : Pre-treatment with DEZ decreases propofol injection pain as effectively as LID The effects of addition of 1 ml of lignocaine ( 10 mg ) or isotonic saline to 19 ml of the emulsified preparation of propofol ( Diprivan ® ) were studied in a r and omised , double – blind trial in 80 patients . The incidence and severity of pain on injection of propofol were significantly reduced by the addition of lignocaine ( P < 0.01 ) Purpose This prospect i ve , double-blind , placebo-controlled study was design ed to determine the efficacy of nitrous oxide ( N2O ) in alleviating the pain that followed sequential injection of propofol and rocuronium . Methods A total of 205 adult patients ( age , 18–68 years ) received one of the following combinations : NaCl and 100 % O2 ( group C ) ; 0.5 mg/kg lidocaine and 100 % O2 ( group L ) ; NaCl and a mixture of 67 % N2O/O2 ( group N ) ; or 0.5 mg/kg lidocaine and a mixture of 67 % N2O/O2 ( group LN ) . Vein occlusion was released after 1 min , and 5 ml propofol was injected over 10 s. Pain was evaluated on a visually enlarged , laminated , numeric rating ( 0–10 ) scale . The remainder of the induction dose of propofol ( with a 3-ml bolus of normal saline and 0.6 mg/kg rocuronium ) was then injected . The response to the rocuronium injection was assessed with a four-point scale ( 0–3 ) . Results The incidence and severity of pain from the propofol injection in groups L , N , and LN were significantly lower than those in group C ( P < 0.001 ) . Frequency and intensity of the withdrawal response were significantly less in groups N and LN than in groups C and L ( no response , P < 0.001 ; severe response , P < 0.001 ) . Conclusions Pretreatment with inhaled N2O can reduce the pain associated with propofol and rocuronium injection . Moreover , N2O ( with or without lidocaine ) is more effective than lidocaine alone in reducing rocuronium-related withdrawal reactions associated with sequential injection of propofol and rocuronium Topical anesthesia using 60 % lidocaine tape reduces the incidence of propofol injection pain . We conducted a r and omized prospect i ve double-blinded placebo-controlled study to assess the analgesic efficacy of pretreatment with topical 5 % lidocaine-prilocaine ( EMLA ) cream in 90 ASA physical status I and II adult patients scheduled to undergo day-case gynecological surgery . Propofol injection pain was not reduced by pretreatment with EMLA cream , whereas the addition of lidocaine to propofol did significantly reduce propofol injection pain compared with the control group ( P = 0.002 ) . We conclude that topical anesthesia with EMLA cream applied for 60 min does not significantly reduce propofol injection pain Objectives To investigate the efficacy of pretreatment with cisatracurium for prevention of pain associated with propofol injection , and compare its efficacy with that of lidocaine . Methods Patients undergoing general anaesthesia were r and omized to receive normal saline ( control group ) , lidocaine ( 0.5 mg/kg ) , 0.03 mg/kg cisatracurium or 0.15 mg/kg cisatracurium . All drugs were administered into the largest dorsal vein of the h and with venous occlusion for 30 s , followed by propofol ( 0.5 mg/kg ) . Pain was evaluated using a four-point scale . Results The incidence and severity of pain was significantly lower in the lidocaine and 0.15 mg/kg cisatracurium groups than the control and 0.03 mg/kg cisatracurium groups ( n = 50/group ) . There was no significant difference between the lidocaine and 0.15 mg/kg cisatracurium groups in the incidence and severity of pain . Conclusions 0.15 mg/kg cisatracurium effectively decreases the incidence and severity of pain induced by propofol injection without any significant complications BACKGROUND Propofol injection pain is a well-known problem in pediatric anesthesia . Premixture of lidocaine with propofol although effective does not abolish injection pain in all children . Promising results have been reported with pretreatment of the vein with ketamine . The purpose of this prospect i ve , double-blind r and omized , clinical trial with active control was to evaluate the efficacy of premixing propofol with ketamine in the prevention of injection pain in children . METHODS After ethics committee and parental approval and children 's assent , 116 children , aged 1 - 12 years , were r and omly allocated to receive an IV induction dose of admixture of racemic ketamine 0.5 mg x ml(-1 ) ( ketamine group ) or lidocaine 1 mg x ml(-1 ) in propofol 10 mg x ml(-1 ) ( lidocaine group ) . The outcome measures were signs and symptoms of injection pain ( primary outcome : the incidence of injection pain ) , hemodynamic and respiratory parameters , and adverse effects during anesthesia induction ( secondary outcomes ) . RESULTS Patients ' characteristics were similar in the two groups . Fewer children ( 13/58 ) in the lidocaine group than in the ketamine group ( 26/58 ) ( mean difference 23 % , 95 % CI for difference 6 - 40 % , P = 0.018 ) developed pain on injection of propofol . There were no differences in hemodynamic parameters between the two groups . One child in the lidocaine group developed laryngospasm , but no other adverse events were recorded . CONCLUSIONS Injection pain was twice as common with ketamine-propofol admixture than with lidocaine-propofol admixture Background and objective : Pain on injection is still a problem with propofol . The purpose of the study was to compare the effectiveness of diphenhydramine and lidocaine on pain caused by propofol at the site of injection . Methods : One hundred and eighty ASA I – II adults undergoing elective surgery were r and omly assigned into three groups of 60 each . Group I ( placebo ) received 2 mL normal saline , Group II received 2 mL ( 40 mg ) 2 % lidocaine and Group III received 2 mL ( 20 mg ) diphenhydramine intravenously ( i.v . ) during a 1‐min venous occlusion , followed by propofol into a cephalic forearm vein of the antecubital fossa . Pain assessment was made immediately after propofol injection . Results : In the placebo group 25 ( 41.7 % ) patients experienced pain during propofol injection as compared to 2 ( 3.3 % ) and 3 ( 5.0 % ) in the lidocaine and diphenhydramine groups , respectively . The prevalence of pain and pain score were significantly less in both the lidocaine and diphenhydramine groups than in the placebo group ( P = 0.00 ) . No difference was found between the diphenhydramine and lidocaine groups ( P = 0.60 ) . Conclusion : Previous injection of diphenhydramine with venous occlusion can be considered as an alternative to lidocaine for reducing the prevalence of pain caused by injection of propofol into peripheral veins Background Aquafol , a microemulsion propofol , causes more severe and frequent pain on injection than propofol . The purpose of this study was to compare a combination of lidocaine and ketamine on aquafol-induced pain with lidocaine or ketamine alone during the induction of anesthesia . Methods In this prospect i ve , r and omized , double-blinded study , 130 healthy patients who were undergoing elective surgery under general anesthesia were enrolled . The patients received IV lidocaine 40 mg plus ketamine 25 mg ( Group LK , n = 43 ) , lidocaine 40 mg ( Group L , n = 42 ) , or ketamine 25 mg ( Group K , n = 45 ) with a rubber tourniquet on the forearm 1 min before the injection of microemulsion propofol . The pain score was assessed by a 4-point verbal rating scale ( VRS ) at 10 seconds after injection of microemulsion propofol 30 mg and during the injection of the remaining total dose . Results The incidence and severity of pain was significantly lower in Group LK than Group L or Group K at 10 seconds after the injection of microemulsion propofol 30 mg ( P < 0.05 ) . And the incidence and severity of pain was significantly lower in Group LK and Group K than Group L during the injection of the remaining total dose ( P < 0.05 ) . Conclusions Pretreatment with IV lidocaine 40 mg plus ketamine 25 mg with a rubber tourniquet on the forearm 1 min before the injection of microemulsion propofol is more effective than lidocaine 40 mg or ketamine 25 mg alone in preventing pain from the injection of microemulsion propofol Using venous retention with a tourniquet ( 70 mm Hg ) , we performed a r and omized , double-blind study to assess the efficacy of IV pretreatment with fentanyl , morphine , meperidine , or lidocaine in reducing propofol injection pain . Immediately after venous occlusion with a tourniquet , IV fentanyl 150 micro g ( Group A , n = 35 ) , morphine 4 mg ( Group B , n = 35 ) , meperidine 40 mg ( Group C , n = 35 ) , 2 % lidocaine 3 mL ( Group D , n = 35 ) , or normal saline 3 mL ( Group E , n = 35 ; as placebo control ) was given to adult patients . The venous retention of the drug was maintained for 1 min , followed by tourniquet release and IV administration of propofol 100 mg . Pain assessment was made immediately after the propofol injection . Lidocaine and meperidine significantly reduced propofol injection pain more than placebo ( P < 0.05 ) , but there were more side effects in the meperidine group . Fentanyl and morphine reduced the intensity of propofol injection pain ( P < 0.05 ) and had some effect in reducing the incidence of propofol injection pain , but the difference did not reach statistical significance . The order of efficacy was lidocaine [ nearly = ] meperidine > morphine [ nearly = ] fentanyl . We postulate that the peripheral analgesic effect of these opioid is due to their local anesthetic activity . Implication s : Propofol , a commonly used anesthetic , often causes pain on injection . Given as venous retention pretreatments 1 min before propofol , meperidine and lidocaine were found to significantly reduce the propofol injection pain , whereas fentanyl and morphine only slightly reduced the propofol injection pain . ( Anesth Analg 1998;86:382 - 6 Bacteriostatic saline is a physiological saline solution containing the bacteriostatic agent benzyl alcohol as a 0.9 % solution . It is used mostly for diluting and dissolving drugs for IV injection and as a flush for intravascular catheters . It also has local anesthetic properties . We studied its efficacy in decreasing the pain associated with IV administration of propofol and compared it with mixing lidocaine with propofol . One-hundred-twenty patients were r and omly allocated into three groups . All patients received propofol 50 mg . The benzyl alcohol group received bacteriostatic saline as a preinjection , and the lidocaine group received propofol containing lidocaine . The placebo group did not receive bacteriostatic saline or lidocaine . Fifteen of 39 patients ( 38 % ) in the benzyl alcohol group complained of pain on injection compared to 33 of 39 ( 84 % ) in the placebo group and 22 of 42 ( 52 % ) in the lidocaine group . Differences were significant between the benzyl alcohol and placebo groups ( P < 0.01 ) and the lidocaine and placebo groups ( P < 0.01 ) . Preinjection with bacteriostatic saline decreases the incidence of pain associated with IV administration of propofol and is comparable to that of mixing lidocaine with propofol Background and objective : Previous studies found that lidocaine addition to propofol long‐chain triglyceride was associated with a lower incidence of injection pain than medium‐chain triglyceride/long‐chain triglyceride formulation , but the incidence was still high ( 31–40 % ) . Our study investigated whether the incidence of injection pain could be further reduced by the addition of lidocaine ( 10 mg , 20 : 1 ) to propofol medium‐chain triglyceride/long‐chain triglyceride . Methods : In a r and omized double‐blind controlled trial 464 patients scheduled to undergo regional anaesthesia were assigned to receive one of the following four options : propofol medium‐chain triglyceride/long‐chain triglyceride + lidocaine , propofol long‐chain triglyceride + lidocaine , propofol medium‐chain triglyceride/long‐chain triglyceride or propofol long‐chain triglyceride . Propofol was injected to reach grade 3 of the Observer ’s Assessment of Alertness/Sedation scale . Results : Incidence of injection pain was 18 % in the propofol medium‐chain triglyceride/long‐chain triglyceride + lidocaine group , 31 % in the propofol long‐chain triglyceride + lidocaine group , 47 % in the propofol medium‐chain triglyceride/long‐chain triglyceride group and 60 % in the long‐chain triglyceride group . Propofol medium‐chain triglyceride/long‐chain triglyceride + lidocaine was associated with a statistically significant reduced incidence of injection pain compared with propofol long‐chain triglyceride + lidocaine ( P = 0.0249 , number needed to treat = 7.7 ) . Conclusions : Premixing propofol medium‐chain triglyceride/long‐chain triglyceride with lidocaine is one of the most effective measures currently available to reduce the incidence of injection pain in se date d patients during regional anaesthesia To eluci date the mechanism of propofol-induced pain on injection , we performed several studies using nafamostat mesilate , a kallikrein inhibitor , or lidocaine . As both pretreatment and low-dose mixing with nafamostat produced the same effects on pain reduction , we used the latter method in the following experiments . Low-dose mixing had the same effect on injection pain as mixing with lidocaine . The extent of pain was assessed by measuring bradykinin concentrations by mixing with blood . Propofol and its lipid solvent mixed with blood produced approximately two-fold generation of bradykinin compared with the saline control , and this was inhibited completely by nafamostat and lidocaine . Injection of the lipid solvent before propofol significantly aggravated pain compared with prior injection of saline , although the lipid solvent injected twice caused no change in pain . These results suggest that the lipid solvent for propofol activates the plasma kallikrein-kinin system and produces bradykinin which modifies the injected local vein . This modification of the peripheral vein may increase the contact between the aqueous phase propofol and the free nerve endings of the vessel , result ing in aggravation of propofol-induced pain & NA ; Propofol has a high incidence of pain with injection , particularly into small veins . We sought to determine whether concomitant administration of lidocaine could prevent this pain . In a r and omized doubleblind trial , 368 women were allocated to one of four groups to receive 19 mL of propofol mixed with either 1 mL of 0.9 % saline , 1 mL of 0.5 % ( 5 mg ) lidocaine , 1 mL of 1 % ( 10 mg ) lidocaine , or 1 mL of 2 % ( 20 mg ) lidocaine . The pain of injection was scored as none , mild , moderate , or severe . There was a significant reduction in the overall incidence of pain from 73 % with saline to 32 % with 20 mg of lidocaine . A highly significant negative dose‐response relationship between the dose of lidocaine and the severity of pain was demonstrable , both at induction of anesthesia and as recalled in the recovery room ( P < 0.001 for both ) . Lidocaine ( 20 mg IV ) will significantly reduce the incidence and severity of pain with propofol injection , but about 6 % of patients will still suffer unpleasant pain if the dorsum of the h and is used We undertook a r and omized , placebo-controlled , double-blind study to compare the use of alfentanil 1 mg and lidocaine 40 mg for the reduction of pain during injection of propofol . Eighty-nine patients were r and omly allocated to one of three groups : Group L , lidocaine 40 mg added to 180 mg propofol ; Group A , alfentanil 1 mg 30 s prior to propofol ; or Group P , placebo ( normal saline ) . The incidence of pain in the placebo group was 67 % . Both treatment groups had a significantly lower incidence of pain than the placebo group ( P < 0.002 ) . There was no significant difference in the incidence of pain between the groups receiving lidocaine or alfentanil ( 13 % and 24 % , respectively ) . There was no significant difference in the induction dose of propofol between the groups . Fifty-two percent of patients who experienced pain at induction had recall of that pain in the recovery room . Alfentanil 1 mg and lidocaine 40 mg are both effective in reducing pain during injection of propofol . ( Anesth Analg 1996;82:469 - 71 BACKGROUND Pain from a propofol injection is a common side-effect in paediatric patients . This prospect i ve , r and omized , double-blind study evaluated the efficacy of a combined pretreatment of alfentanil with lidocaine on the incidence and severity of propofol injection pain in children . METHODS After obtaining parental consent , 120 paediatric patients were allocated r and omly into one of the three groups ( n=40 , in each ) . The patients in the alfentanil group received alfentanil 15 microg kg(-1 ) 90 s before the propofol injection . The patients in the lidocaine group received propofol 3 mg kg(-1 ) premixed with lidocaine 0.1 % over a 15 s period . The patients in the combination group received both alfentanil and lidocaine . RESULTS The incidence of propofol injection pain ( severity 2 or more ) in the combination group ( 2.6 % ) was significantly lower than that in the alfentanil and lidocaine groups ( 30 % and 38.5 % , respectively ) ( P=0.001 and < 0.001 , respectively ) . No patient in the combination group complained of moderate or severe pain from propofol injection . CONCLUSIONS Our study demonstrated that the combination treatment of two different analgesic modalities , alfentanil and lidocaine , could prevent the moderate and severe pain on propofol injection , and reduce the incidence of mild pain compared with each drug alone BACKGROUND Propofol is associated with a high incidence of injection pain in children , even if given together with lidocaine . A new lipid formulation of etomi date ( Etomi date -Lipuro ) has been found in adults to cause very little discomfort during i.v . injection . The aim of the present prospect i ve , double-blind , r and omized trial was to compare the incidence of injection pain during i.v . induction of anaesthesia between propofol with added lidocaine ( previous st and ard ) and this new etomi date formulation in paediatric patients . METHODS A total of 110 paediatric patients , aged 2 - 16 years , scheduled for outpatient surgery were planned to be included in the study . The primary end point of the study was the incidence of injection pain during induction of anaesthesia as assessed by a four-point scale as described previously . The occurrence of myoclonic muscular activity was registered as a secondary end point ( four-point scale ) . An interim analysis after 80 patients was requested by the Ethics ' Committee . RESULTS The study was stopped after the inclusion of 80 patients . A significantly lower incidence of injection pain was found in the Etomi date -Lipuro group as compared with the propofol-lidocaine group ( 5.0 % vs 47.5 % , P<0.001 ) . The use of etomi date was associated with a significantly higher incidence of myoclonic activity compared with propofol-lidocaine ( 85.0 % vs 15 % , P<0.001 ) . CONCLUSIONS The use of a new lipid formulation of etomi date is associated with significantly less injection pain than propofol with added lidocaine in children . This finding may warrant a change in clinical practice in order to avoid unnecessary pain in children Background : Propofol is one of common anesthetic drugs used in anesthesia . The most common side effects of propofol are local pain . Pretreatment with lidocaine can reduce propofol injection pain . Objectives : The aim of the present study was to assess and compare the efficiency of lidocaine 0.4 % and 2 % in reducing the incidence and severity of propofol injection pain . Patients and Methods : This was a double blind prospect i ve clinical trial on children 4 - 8 years old with class ASA I and II c and i date s who were referred to Dr. Shaikh Hospital in Mashhad for elective surgery . Sample size calculated 50 patients in each groups based on pilot study . 100 children 's were r and omly divided equally in two groups , who were injected with lidocaine solutions 2 % and 0.4 % respectively . patient 's pain evaluation based on VSD ( verbal descriptor scale ) and NRS ( Numeric Rating Scale ) using patient 's verbal reaction and behavior namely fretting , h and drag and tearing . The collated data was analyzed . Results : There was nosignificant difference as to the first three variables ( age , gender and weight P > 0.2 ) . The significant difference regarding pain experience in both groups was noteworthy ( P > 0.2 ) . Conclusions : Most of the studies compared lidocaine with other drugs or its efficiency at different doses . Our study is different in that we applied a constant dose of lidocaine in various volumes and concentration . This result shows that lidocaine with the same does but lower concentration and higher volume is more effective in preventing propofol injection pain . Using diluted lidocaine with the dosage of 1 mg/kg and a concentration of 0.4 % is an effective way to relieve pain caused by propofol injection in children Background A microemulsion propofol causes a high incidence of pain during intravenous injection . In this study , we investigated the effect of ramosetron on pain induced by microemulsion propofol injection . Methods After prospect i ve power analysis and institutional review board approval , a total of 200 ASA I and II patients undergoing general anesthesia were divided into 4 groups . They received one of the following intravenously after tourniquet application on the forearm 1 min before induction of anesthesia using microemulsion propofol ; normal saline ( Group N , n = 50 ) , lidocaine 20 mg ( Group L , n = 50 ) , ramosetron 0.3 mg ( Group R , n = 50 ) and lidocaine 20 mg plus ramosetron 0.3 mg ( Group LR , n = 50 ) diluted into a 5 ml solution . The occlusion was released after 30 seconds and microemulsion propofol was injected over 10 - 15 seconds . The patients were observed and asked immediately if they had pain in the arm , and their responses were assessed . Results The incidence of pain in groups N , L , R and LR was 96 % , 76 % , 60 % and 38 % , respectively ( P < 0.008 ) . Two patients in Group LR ( 4.0 % ) and nine in Group R ( 18.0 % ) had moderate to severe pain , which was significantly lower than pain in Groups N ( 84.0 % ) , L ( 40.0 % ) and R ( P < 0.008 ) . Conclusions Pretreatment with ramosetron 0.3 mg with or without lidocaine 20 mg with a tourniquet on the forearm 30 seconds before the injection of microemulsion propofol is more effective than lidocaine 20 mg or normal saline in preventing pain from a microemulsion propofol injection BACKGROUND Pain on injection limits the use of propofol in children . The combination of lidocaine and propofol is widely used to reduce pain . A new solvent [ medium-chain triglyceride (mct)/long-chain triglyceride ( lct ) ] has been advocated to be less painful than st and ard ( lct ) propofol in adults , but no information is available of its usefulness in pre-school children . We design ed a prospect i ve , r and omized , double-blinded , placebo-controlled study to assess injection pain with two different propofol emulsions , each given with or without lidocaine in children < 7 yr . METHODS A total of 160 ASA I-III children were r and omly assigned to receive lct-propofol or mct/lct-propofol , 5 mg kg(-1 ) , with lidocaine 10 mg ml(-1 ) or saline . The site and size of venous cannulation and restlessness before injection were recorded in each patient . A pain score grade d 0 - 6 was established based on spontaneous verbal and motor reaction during injection , each grade d 0 - 3 . Kruskall-Wallis and Mann-Whitney tests were used for statistical analysis . RESULTS Median pain scores decreased in all groups compared with lct-propofol-saline ( P<0.001 ) and were least in the lct/mct-propofol-lidocaine group ( P<0.001 ) . Painless injection ( score , 0 - 2 ) occurred in 92.5 % of patients in the mct/lct-propofol-lidocaine group compared with 41 - 77 % in the others ( P<0.001 ) . CONCLUSIONS Mct/lct-propofol caused significantly less pain than lct-propofol in preschool children . Mixing of lidocaine with mct/lct-propofol result ed in a further significant decrease , virtually eliminating the pain on injection BACKGROUND Propofol injection pain is a frequent and a well-known complaint distressing for the patients . Although the ethiology of this pain remains obscure , the ideal method for the prevention of propofol injection pain is still controversial . Local anesthetics , opioids , nonsteroidal anti-inflammatory drugs , ketamine , metoclopramide , droperidol have been tested . We aim ed to conduct a study comparing various drugs with saline , lidocaine and together at the same time . METHODS In this r and omized , double-blind , prospect i ve trial a total of 250 patients ( ASA I-II ) undergoing elective surgery with general anesthesia were r and omly allocated into five groups . After premedication of 3 mg midazolam i m , patients received either 2 mL ( 0.02 mg ) of remifentanil ( n = 50 , Group R ) , 2mL ( 40 mg ) of lidocaine ( n = 50 , Group L ) , 2 mL ( 10 mg ) of metoclopramide ( n = 50 , Group M ) , or 2mL ( 100 microg/kg ) of ketamine ( n = 50 , Group K ) and 2 mL of saline . Pain intensity was evaluated through the use of a verbal rating scale , 0 = none , 1 = mild pain , 2 = moderate pain , and 3 = severe pain . RESULTS Pretreatment with remifentanil 0.02 mg , % 2 lidocaine 40 mg , metoclopramide 10 mg , and ketamine 100 microg/kg yields propofol induced pain 38 % , 76 % , 76 % , and 58 % respectively . Pretreatment with lidocaine or metoclopramide equally and significantly reduced the incidence and severity of propofol induced pain ( 76 % ) . CONCLUSION Lidocaine and metoclopramide were equally and the most effective treatments in attenuating pain during intravenous injection of propofol compared to pretreatment with remifentanil and ketamine BACKGROUND Different methods and propofol formulations have been used to decrease propofol injection pain , but it remains an unresolved problem . We aim ed to investigate the effect of i.v . acetaminophen pretreatment on the propofol injection pain . METHODS One hundred and fifty ASA I-II patients undergoing general anaesthesia were r and omly allocated into three groups . A 20-gauge catheter was inserted into a superficial radial vein of the left h and , and after the occlusion of venous drainage , Groups I , II , and III were pretreated with 40 mg of lidocaine in saline , 50 mg of i.v . acetaminophen , and 5 ml of saline , respectively . The occlusion was released after 2 min and one-fourth of the total propofol dose was injected into the vein over a period of 5 s. During the injection of both pretreatment solution and propofol , patients ' pain was assessed and recorded as 0 - 3 , corresponding to no , mild , moderate or severe pain , respectively . Chi2 and Kruskal-Wallis tests were used for the statistical analysis . For all analyses , differences were considered to be significant at P<0.05 . RESULTS Patient characteristics were similar among the groups . Incidence of pain on injection of propofol in control , i.v . acetaminophen , and lidocaine groups was 64 % , 22 % and 8 % , respectively ( P<0.05 ) . CONCLUSIONS Pretreatment with i.v . acetaminophen seems to be effective in attenuating pain during i.v . injection of propofol Background Microemulsion propofol produces more frequent and severe pain upon injection than lipid emulsion propofol . This study examined the analgesic effect of lidocaine-premixed microemulsion propofol in patients pretreated with remifentanil . The induction of anesthesia with this combination was compared with microemulsion propofol accompanied with either remifentanil or lidocaine . Methods One hundred twenty patients aged between 20 - 65 years old were allocated r and omly into one of three groups ( n = 40 , in each ) . The patients in the remifentanil group received remifentanil 0.5 µg/kg IV for 30 seconds before a microemulsion propofol injection . The patients in the lidocaine group received propofol 2 mg/kg premixed with 40 mg lidocaine over a 60 second period . The patients in the combination group received both remifentanil and lidocaine . Results There was a significantly lower incidence of microemulsion propofol injection pain ( severity 2 or more ) in the combination group ( 12.5 % ) than in the remifentanil and lidocaine groups ( 90 % and 65 % , respectively , P < 0.05 ) . The incidence of moderate pain disappeared completely in the combination group ( 0 % ) compared to that in the remifentanil and lidocaine group ( 32.5 % and 20 % , respectively , P < 0.05 ) . Severe pain did not appear in any of the three groups . There were no complications on the injection site in the lidocaine alone and combination groups . Conclusions The combination of microemulsion propofol premixed with lidocaine after a pretreatment with remifentanil was more effective in reducing the incidence of pain upon the injection of microemulsion propofol than either treatment alone BACKGROUND : IV injection of propofol during anesthetic induction induces pain . Ketamine has been shown to reduce injection pain . In this study , we established the optimal dose of ketamine to prevent the pain of injection with propofol . METHODS : Two hundred forty patients presenting for elective surgery were r and omly allocated into eight groups ; five groups during the first part of the study and three groups during the second part . In Part 1 , patients received saline ( Group S ) , lidocaine ( Group L ) , ketamine 10 & mgr;g/kg ( Group K10 ) , 50 & mgr;g/kg ( Group K50 ) , or 100 & mgr;g/kg ( Group K100 ) , respectively , immediately followed by propofol 2.5 mg/kg . In Part 2 , the optimal dose of ketamine ( 100 & mgr;g/kg ) was administered 3 min before propofol ( Group Pre ) , mixed with propofol solution ( Group KP ) , or after oral midazolam premedication ( Group M ) . An anesthesiologist blinded to the study group monitored each patient ’s pain score at 5-s intervals . RESULTS : In Part 1 , the incidence and intensity of pain were the lowest in the K100 and L groups ( P < 0.001 ) . In Part 2 , the patients in the K100 and M groups had significantly lower pain scores compared with the KP and Pre groups ( P < 0.05 ) . During induction , there were no significant intergroup differences in mean arterial blood pressure and heart rate in all groups . CONCLUSIONS : Administration of ketamine 100 & mgr;g/kg immediately before propofol injection provided the optimal dose and timing to reduce propofol-induced pain on injection Background : Metoclopramide administered intravenously ( iv ) immediately before injection of propofol , after mixing with propofol , or after a rubber tourniquet for 1 min before propofol injection will reduce pain induced by propofol injection . In this study , these three different techniques in reducing propofol injection pain with metoclopramide were compared with lidocaine or saline to evaluate the most effective method in reducing propofol injection pain Purpose Propofol injection pain , despite various strategies , remains common and troublesome . This study aim ed to test the hypothesis that pretreatment with the combination of intravenous lidocaine and magnesium would have an additive effect on reducing propofol injection pain . Methods After institutional review board ( IRB ) approval and informed consent , we performed a prospect i ve , double-blind , placebo-controlled , r and omized trial . Subjects were r and omly assigned to pretreatment with either lidocaine ( 50 mg ) , magnesium sulfate ( 0.25 mg ) , lidocaine ( 50 mg ) plus magnesium sulfate ( 0.25 mg ) , or 0.9 % sodium chloride . Following pretreatment , propofol ( 50 mg ) was administered , and subjects were question ed regarding injection site pain and observed for behavioral signs of pain . Results Two hundred subjects were enrolled and 158 subjects ( 39 placebo , 38 lidocaine , 44 magnesium sulfate , and 37 lidocaine plus magnesium sulfate ) received their assigned pretreatment intervention . Intergroup baseline characteristics were similar . The proportion of subjects reporting propofol injection pain was highest in those pretreated with magnesium sulfate ( 57 % ) , followed by those pretreated with placebo ( 46 % ) , lidocaine plus magnesium sulfate ( 41 % ) , and then lidocaine ( 29 % ; p = 0.011 ) . When adjusted for age , gender , diabetes mellitus , chronic pain , tobacco use , and selective-serotonin reuptake inhibitor use , the pain response scale scores were significantly reduced by lidocaine pretreatment compared to magnesium sulfate and placebo ( p = 0.031 and p = 0.0003 , respectively ) . Conclusions In this double-blind , placebo-controlled , r and omized trial , the combination of intravenous magnesium sulfate and lidocaine offered no additional benefit for the relief of propofol injection pain compared to intravenous lidocaine alone . An improved , receptor-based underst and ing of the mechanism of propofol injection pain is still needed Background Similar to lipid emulsion propofol , microemulsion propofol also causes a high incidence of pain during intravenous injection . Various methods have been used to minimize the incidence and severity of pain on injection of lipid emulsion propofol . In this study , we investigated the effect of a lidocaine mixture on pain induced by microemulsion propofol injection , and sought to determine the optimal dose of lidocaine that could reduce pain on injecting a propofol-lidocaine mixture . Methods One hundred sixty ( n = 160 ) patients of American Society of Anesthesiologists physical status class I or II were r and omly allocated to four groups : Group A , control ; Group B , 20 mg lidocaine ; Group C , 30 mg lidocaine ; Group D , 40 mg lidocaine . In each patient , pain on microemulsion propofol solution injection was grade d as none , mild , moderate , or severe . Results The incidence of pain in groups A , B , C , and D was 97.5 % , 80 % , 65 % , and 50 % , respectively . Increasing the lidocaine dose significantly reduced pain ( P < 0.05 ) . One patient in Group D ( 2.5 % ) had moderate to severe pain , which was significantly lower than groups B ( 42.5 % ) and C ( 32.5 % ) ( P < 0.05 ) . Conclusions The lidocaine and propofol mixture is effective in alleviating pain associated with microemulsion propofol injection . Within this dose range and in this patients population , increasing lidocaine dosage significantly reduced pain during injection of microemulsion propofol PURPOSE Propofol is a popular i.v . anesthetic induction drug that causes pain when given i.v . , the incidence of which is between 28%-90 % . We plan to determine the optimal dose of ketamine in the prevention of propofol injection pain and compare it with lidocaine , the commonly proposed pre-treatment . METHODS In a double-blind r and omized study 500 Patients ( ASA I , II ) scheduled for elective strabismus surgery under general anesthesia were r and omly allocated into five groups . After obtaining the informed consent . , patients received normal saline ( Group NS ) , lidocaine 1 mg x kg(-1 ) ( Group L ) , and different doses of ketamine 50 - 75 - 100 microg x kg(-1 ) ( Group K50-K75-K100 respectively ) , immediately before the injection of 2.5 mg.kg(-1 ) propofol . Each patient 's pain scores were measured at five seconds intervals by a blinded anesthesiologist . Statistical analysis were made by SPSS vs 11.5 . RESULTS The incidence and intensity of pain in all study groups were significantly lower than placebo group ( Group NS ) ( P < 0.005 ) . Patients in the K100 Group had significantly lower incidence of pain and lower pain scores compared with the K50 and L Groups ( P < 0.0001 ) . There were no significant differences in hemodynamic parameters between groups . CONCLUSION Administration of ketamine 100 microg x kg(-1 ) immediately before propofol injection is a safe and effective method in preventing propofol injection pain Propofol , a commonly used anesthetic , often causes pain on injection . Several methods have been described to reduce this pain , however , complete inhibition has not been achieved . Our r and omized , placebo controlled , double blind study has been conducted to compare the analgesic efficacy of iv pretreatment of ketamine , meperidine , thiopental , lidocaine to minimize the injection pain of propofol . 125 patients ASA I and II were r and omly allocated into 5 groups and received . Group K , ketamine 0.4 mg/kg ; Group T , thiopental 0.5 mg/kg ; Group M , meperidine 0.5 [ corrected ] mg/kg ; Group L , lidocaine 1 mg/kg ; Group S , saline 3 ml . All pretreatment drugs were made into 4 ml solutions and were accompanied by manual venous occlusion for 1 min , followed by tourniquet release and slowly IV administration of propofol . Pain was assessed with a four point scale . All treatment groups had a significantly lower incidence of pain than placebo group ( p < 0.05 ) . However , it has been observed that pretreatment with ketamine was the most effective in attenuating pain associated with propofol injection ( p < 0.05 ) . For painless injection of propofol , routine pretreatment with ketamine 0.4 mg/kg along with venous occlusion is recommended Background s and objective : There is a high incidence of pain following intravenous injection of propofol , and many studies have been conducted to find a way of reducing this . The administration of lidocaine and , recently , remifentanil has also been used for this purpose , but it is only partially effective . Thus , the purpose of this study was to investigate the analgesic effect of a combination of pretreatment with remifentanil and premixture of lidocaine with propofol and to compare either treatment alone during propofol injection in dorsal h and ‐veins . Methods : In a prospect i ve , r and omized , double‐blinded trial , we studied 141 adult patients scheduled for elective surgery . The combination of pretreatment of remifentanil ( 0.35 & mgr;g kg−1 min−1 ) and a premixture of lidocaine with propofol ( mixture of propofol 1 % and lidocaine 1 % in a 10 : 1 ratio ) was compared with either treatment alone in the prevention of pain on propofol injection . Pain was assessed on a four‐point scale ( 0 = none , 1 = mild , 2 = moderate , 3 = severe ) during propofol injection . Patients in Group B received remifentanil ( 0.35 & mgr;g kg−1 min−1 ) 30 s before the injection of propofol . Results : The reduction of pain on propofol injection was similar in both the remifentanil pretreatment and lidocaine premixture groups ( 62.2 % vs. 62.2 % ) . Combination therapy was associated with a higher incidence of patients without pain ( 91.3 % ) than either treatment alone ( P < 0.001 ) . On analysing the injection pain scores , we found a significant reduction of the score in the remifentanil and lidocaine Group C compared with the lidocaine Group A ( P < 0.001 ) and the remifentanil Group B ( P < 0.001 ) . Conclusions : The combination of pretreatment of remifentanil and premixture of lidocaine with propofol was more effective in reducing the incidence of pain on injection of propofol than either treatment alone In a r and omised , controlled , double‐blinded trial to study the effect of ondansetron pretreatment on the pain produced after intravenous injection of rocuronium and propofol in comparison with lidocaine , 60 patients were r and omly assigned to one of three groups . Group 1 received 5 ml of intravenous 0.9 % sodium chloride solution pretreatment , group 2 received ondansetron 4 mg ( 2 mg.ml−1 solution ) diluted into a 5‐ml solution , and group 3 received 50 mg lidocaine ( 5 ml 1 % solution ) ; this was followed 1 min later by rocuronium and propofol . Pain was reduced significantly in the ondansetron and lidocaine groups ( p < 0.0001 ) compared with placebo , and significantly better with lidocaine than with ondansetron ( p = 0.02 ) . We conclude that ondansetron is effective in relieving the pain of rocuronium but is not as effective as lidocaine Purpose Propofol produces anesthesia with rapid recovery . However , it causes pain or discomfort on injection . A number of techniques have been tried for minimizing propofol-induced pain with variable results . We have compared the efficacy of magnesium and lidocaine for the prevention of propofol induced pain . Methods Three hundred ASA I and II adults undergoing elective surgery were r and omly assigned into three groups of 100 each . Group I received magnesium sulfate 1 g , Group II received lidocaine 2 % ( 40 mg ) and Group III received normal saline , all in a volume of 2 mL and accompanied by venous occlusion for one minute . Induction with propofol 2.5 mg·kg−1 was accomplished following the release of venous occlusion . Pain was assessed on a four-point scale : 0 = no pain , 1 = mild pain , 2 = moderate pain , and 3 = severe pain at the time of pretreatment and propofol injection . Results were analyzed by ‘ Z ’ test . A P value of < 0.05 was considered as significant . Results Pain during iv pretreatment with magnesium was 31 % as compared to 2 % for both the lidocaine and control groups ( P < 0.05 ) . Seventy-six percent of patients in the control group had pain during iv propofol as compared to 32 % and 42 % in the magnesium and the lidocaine groups respectively ( P < 0.05 ) . Lidocaine and magnesium pretreatment were equally effective in attenuating pain during the propofol injection ( P > 0.05 ) . Conclusions Intravenous magnesium and lidocaine pretreatment are equally effective in attenuating propofol-induced pain . However , magnesium pretreatment itself causes pain . Therefore , there is no justification in the use of magnesium pretreatment for attenuating pain associated with iv propofol . RésuméObjectifLe propofol produit une anesthésie do nt la récupération est rapide . Son injection cause toutefois de la douleur ou de l’inconfort . On a tenté de réduire cette douleur au moyen de quelques techniques aux résultats variables . Nous avons comparé l’efficacité du magnésium et de la lidocaïne pour prévenir la douleur induite par le propofol . MéthodeTrois cents adultes d’état physique ASA I et II devant subir une intervention chirurgicale réglée ont été aléatoirement répartis en trois groupes égaux . Ceux du groupe I ont reçu 1 g de sulfate de magnésium , ceux du groupe II , 40 mg de lidocaïne à 2 % et ceux du groupe III , une solution saline , tous dans un volume de 2 mL et accompagnés d’une occlusion veineuse d’une minute . L’induction avec 2,5 mg·kg−1 de propofol a été réalisée après la levée de l’occlusion veineuse . La douleur a été évaluée selon une échelle en quatre points : 0 = aucune douleur , 1 = douleur légère , 2 = douleur modérée et 3 = douleur sévère , au moment du prétraitement et de l’injection de propofol . Les résultats ont été analysés par le test « Z » . Une valeur de P < 0,05 était considérée significative . RésultatsLa douleur du prétraitement iv au magnésium a été de 31 % , et de 2 % pour la lidocaïne et la solution salée ( P < 0,05 ) . On a noté que 76 % des témoins , mais 32 % et 42 % des patients des groupes magnésium ou lidocaïne , respectivement ( P < 0,05 ) ont eu des douleurs à l’injection iv de propofol . La lidocaïne et le magnésium ont une action similaire comme prétraitement de la douleur causée par le propofol ( P > 0,05 ) . Conclusions Les prétraitements intraveineux au magnésium et à la lidocaïne réduisent de façon similaire la douleur induite par le propofol . Mais le prétraitement au magnésium peut lui-même être douloureux . Rien ne justifie donc son usage pour atténuer la douleur associée à l’injection iv de propofol We determined whether pretreatment with topical 60 % lidocaine tape reduced the incidence of pain on injection of propofol compared with mixing intravenous lidocaine with propofol . In a r and omized , double-blind trial , 90 patients were allocated to one of three groups : pretreatment with a bioocclusive dressing and administration of a premixed solution of propofol 180 mg and 2 mL of normal saline ( Group A ) ; pretreatment with 60 % lidocaine tape and a premixed solution of propofol and normal saline ( Group B ) ; or pretreatment with a bioocclusive dressing and a premixed solution of propofol 180 mg and lidocaine 40 mg ( Group C ) . The incidences of pain in Groups A , B , and C were 86.7 % , 33.4 % , and 20 % , respectively . Group B and Group C had a significantly lower incidence of pain than Group A. There was no significant difference in the incidence of pain between Group B and Group C. There was no significant difference in the distribution of site of pain on injection of propofol among the three groups . Pretreatment with topical 60 % lidocaine tape reduced the incidence of pain on injection of propofol similar to that of intravenous lidocaine mixed with propofol . Implication s : Pretreatment with topical 60 % lidocaine tape reduces the pain associated with injection of propofol , a frequently used intravenous anesthetic . This approach should increase patient comfort during induction of anesthesia . ( Anesth Analg 1997;85:672 - 4 Propofol is frequently associated with pain on injection . Previous studies have suggested that chilling of the propofol decreases pain significantly . This prospect i ve , r and omised , double‐blind trial was design ed to assess the effectiveness of cold propofol compared with propofol premixed with lignocaine in minimising pain on injection . Patients were allocated to one of four groups : propofol + lignocaine 0.1 mg.kg−1 , propofol + lignocaine 0.2 mg.kg−1 , cold propofol and a control group consisting of propofol premixed with normal saline and maintained at room temperature . The results of this study show that cold propofol is associated with a very high incidence of injection pain while lignocaine 0.1 mg.kg−1 premixed with propofol significantly decreases the incidence of pain ( p < 0.001 ) . Increasing the dosage of lignocaine above 0.1 mg.kg−1 , however , does not significantly decrease the incidence of pain further . The addition of lignocaine also significantly decreases the incidence of excitatory side‐effects STUDY OBJECTIVE To evaluate the influence of aging on lidocaine requirements for propofol-induced pain on injection . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING The study was undertaken at a University hospital . PATIENTS 160 ASA physical status I and II adult patients scheduled for elective surgery with general anesthesia . INTERVENTIONS Patients received placebo ( saline ) or lidocaine intravenously at three different doses ( 10 , 20 , or 40 mg ) , with venous occlusion for two minutes , followed by injection of propofol 0.5 mg/kg into a dorsal h and vein . MEASUREMENT AND MAIN RESULTS Pain during injection of propofol was evaluated . For young patients , the frequency of propofol-induced pain was 70 % in patients receiving lidocaine 10 mg ( P = not significant ) ; 50 % in those receiving lidocaine 20 mg ( P = not significant ) ; and 30 % in those receiving lidocaine 40 mg ( P < 0.05 ) , compared with placebo ( 80 % ) . For elderly patients , 15 patients ( 75 % ) complained of pain in the placebo group , compared with 13 ( 65 % ) in the lidocaine 10 mg group ( P = not significant ) ; 5 ( 25 % ) in the lidocaine 20 mg group ( P < 0.05 ) ; and 4 ( 20 % ) in the lidocaine 40 mg group ( P < 0.05 ) . CONCLUSIONS A lidocaine dose of 40 mg for young patients and 20 mg for old patients , with venous occlusion for two minutes , is sufficient to reduce pain on injection of propofol A controlled r and omised double‐blind design was used to study the effect of lignocaine on the pain produced by intravenous injection of propofol . Patients received a 2‐ml pretreatment solution with temporary venous occlusion , followed by an induction solution . One hundred and three patients were assigned to one of five groups : saline pretreatment , followed by induction with propofol plus saline 2 ml ; lignocaine 20 mg pretreatment , followed by induction with propofol plus saline 2 ml ; lignocaine 40 mg pretreatment , followed by induction with propofol plus saline 2 ml ; saline pretreatment , followed by induction with propofol plus lignocaine 20 mg ; or saline pretreatment , followed by induction with propofol plus lignocaine 40 mg . Pain was reduced significantly in all groups in which lignocaine was used and a dose of 40 mg was more effective than 20 mg . There were no significant differences in the incidence of pain among the groups which received lignocaine as pretreatment and the groups which received lignocaine mixed with propofol . Sixty‐eight percent of patients who experienced pain or discomfort recalled it in the postoperative period BACKGROUND Pain during the injection of propofol is a common clinical problem . Lidocaine pretreatment , preceded by venous occlusion , is the most popular method for reducing pain during the injection of propofol but can not entirely control such pain . We aim ed to evaluate the efficacy of lidocaine , flurbiprofen axetil ( an injectable prodrug of flurbiprofen ) , and the two in combination for reducing pain during the injection of propofol . METHODS This prospect i ve , r and omized , double-blind , placebo-controlled study was conducted at the Department of Anesthesiology , Ushiku Aiwa General Hospital , Ibaraki , Japan . One hundred patients , 55 men and 45 women aged 22 - 69 years old and with ASA physical statuses of I-II , were r and omly allocated to one of four groups to receive intravenously placebo ( saline ) , lidocaine 40 mg , flurbiprofen axetil 50 mg , or both ( N=25 for each group ) , with venous occlusion for 2 minutes , followed by administration of propofol 0.5 mg/kg into a dorsal h and vein . A blind research er asked the patients to assess pain during injection of propofol . RESULTS The treatment groups were comparable with respect to patient characteristics . The overall incidence of propofol-induced pain was 32 % with lidocaine ( P=0.001 ) , 40 % with flurbiprofen axetil ( P = 0.001 ) , and 8 % with both ( P=0.001 ) , compared with 88 % with placebo . The incidence of such pain was lower in patients receiving the lidocaine/flurbiprofen axetil combination than in those receiving lidocaine or flurbiprofen ( P=0.036 , combination vs. lidocaine ; P=0.009 , combination vs. flurbiprofen axetil ) . CONCLUSION The lidocaine/flurbiprofen axetil combination , compared with lidocaine 40 mg or flurbiprofen 50 mg , effectively reduces pain during the injection of propofol Purpose To investigate if 50 % nitrous oxide reduces the pain during injection of propofol mixed with lidocaine in children . Methods Healthy children undergoingiv induction of general anesthesia for elective surgery were recruited into this prospect i ve , r and omized , double-blind study . None of the patients received any premedication except for eutectic mixture of local anesthetics cream . Before induction of anesthesia with propofol 1 % mixed with lidocaine 0.05 % ( propofol dose 3 mg·kg−1 ) , the treatment group received 50 % N2O in O2 and the control group received 100 % oxygen . Pain due to propofol administration was rated with a four-point behavioural scale : none , mild , moderate or severe . Results There were 28 subjects in the control group and 26 subjects in the treatment group . Demographic data were similar in both groups . The incidence of pain at induction was 4 % after N2O and 36 % in the control group , P < 0.01 . No patients had severe pain . Most patients had mild pain . Three of the ten patients with pain in the control group had moderate pain . The number needed to treat was 3:1 . Conclusion Nitrous oxide reduces pain during induction with propofol mixed with lidocaine in healthy children . RésuméObjectifVérifier si du protoxyde d’azote à 50 % peut réduire la douleur de l’injection d’un mélange de propofol et de lidocaïne chez des enfants . MéthodeDes enfants en bonne santé devant subir l’induction intraveineuse d’une anesthésie générale , pour une intervention non urgente , ont participé à une étude prospect i ve , r and omisée et à double insu . Aucun enfant n’a reçu de prémédication , sauf un mélange eutectique de crème anesthésique locale . Avant l’induction de l’anesthésie avec un mélange de propofol à 1 % et de lidocaïne à 0,05 % ( 3 mg·kg−1 de propofol ) , les enfants du groupe expérimental ont reçu un mélange de N2O et de O2à 50 % et les enfants témoins , 100 % d’oxygène . La douleur causée par l’administration de propofol a été cotée selon une échelle en quatre points : aucune douleur , douleur légère , modérée ou sévère . RésultatsLe groupe témoin comprenait 28 sujets et le groupe expérimental , 26 . Les données démographiques étaient comparables entre les groupes . L’incidence de douleur à l’induction a été de 4 % après l’administration de N2O et de 36 % chez les témoins , P < 0,01 . Aucun patient n’a éprouvé de douleur sévère . La plupart n’ont subi que de légères douleurs . Trois des dix patients qui ont présenté des douleurs dans le groupe témoin ont eu des douleurs modérées . Le nombre nécessaire pour traiter a été de 3:1 . Conclusion Le protoxyde d’azote réduit la douleur pendant l’induction de l’anesthésie avec un mélange de propofol et de lidocaïne chez des enfants en bonne santé OBJECTIVE To study the effect of the venous occlusion duration using lidocaine on the incidence and severity of propofol induced pain . METHODS A prospect i ve double-blind r and omized study was design ed at Jordan University Hospital , Amman , Jordan between October 2007 and November 2007 . One hundred and fifty patients aged 14 - 70 years , American Society of Anesthesiologists ( ASA ) clinical status I and II who underwent elective surgeries under general anesthesia , were divided into 3 groups . All 3 groups had propofol 1 % infusion at a constant rate after applying venous occlusion with lidocaine . The occlusion was applied for 15 seconds ( group I , n=50 ) , 30 seconds ( group II , n=50 ) and 60 seconds ( group III , n=50 ) . Pain was assessed during injection according to a verbal pain score . RESULTS Fourteen patients 28 % had pain in group I , compared to 16 patients 32 % in group II , and 9 patients 18 % in group III . This difference did not reach statistical significance p>0.05 for the incidence and severity of pain . CONCLUSION While venous occlusion with lidocaine is an effective method in relieving propofol induced pain , we found no difference when the duration of venous occlusion was 15 , 30 , or 60 seconds Propofol causes pain on IV injection in 28%–90 % of patients . A number of techniques have been tried to minimize propofol-induced pain , with variable results . We compared the efficacy of pretreatment with thiopental 0.25 mg/kg and 0.5 mg/kg and lidocaine 40 mg after venous occlusion for prevention of propofol-induced pain . One-hundred-twenty-four adult patients , ASA physical status I – II , undergoing elective surgery were r and omly assigned into 4 groups of 31 each . Group I received normal saline , group II received lidocaine 2 % ( 40 mg ) , and groups III and IV received thiopental 0.25 mg/kg and 0.5 mg/kg , respectively . All pretreatment drugs were made in 2 mL and were accompanied by manual venous occlusion for 1 min . Propofol was administered after release of venous occlusion . Pain was assessed with a four-point scale : 0 = no pain , 1 = mild pain , 2 = moderate pain , and 3 = severe pain at the time of propofol injection . Twenty-four patients ( 77 % ) complained of pain in the group pretreated with normal saline as compared with 12 ( 39 % ) , 10 ( 32 % ) , and 1 ( 3 % ) in the groups pretreated with lidocaine 40 mg , thiopental 0.25 mg/kg , and thiopental 0.5 mg/kg , respectively ( P < 0.05 ) . Thiopental 0.5 mg/kg was the most effective treatment . We therefore suggest routine pretreatment with thiopental 0.5 mg/kg along with venous occlusion for 1 min for prevention of pain associated with propofol injection STUDY OBJECTIVE To determine the optimal concentration of lidocaine that reduces pain on injection of a propofol-lidocaine mixture . DESIGN Prospect i ve , r and omized , double-blinded , clinical investigation . SETTING Medical center , university teaching hospital . PATIENTS 240 ASA physical status I and II female out patients , aged 21 to 65 years , undergoing dilation and curettage with propofol for anesthesia induction . INTERVENTIONS Patients were r and omized to one of four groups in double-blinded fashion . In Group A ( control ) , patients were given propofol containing normal saline ; in Group B , Group C , and Group D , patients received propofol containing 0.05 % lidocaine ( Group B ) , propofol containing 0.1 % lidocaine ( Group C ) , and propofol containing 0.2 % lidocaine ( Group D ) for induction . MEASUREMENTS AND MAIN RESULTS The incidence of pain on injection of propofol was significantly decreased in Group C and Group D ( 8.3 % and 10.0 % , respectively ) in comparison to the control group ( 91.7 % ) ( p < 0.001 ) . Although the result in Group B ( 76.7 % ) was better than that in the control group , the difference was not statistically significant . No significant difference was seen between Group C and Group D. CONCLUSIONS The optimal effective concentration of lidocaine , which decreased the incidence of pain caused by propofol injection , was 0.1 % in the currently studied population BACKGROUND Pain on injection was a disadvantage of propofol long-chain triglyceride ( LCT ) and reduces patient satisfaction . Based on a systematic review , the recommended method to attenuate this pain was a previous administration of lidocaine under tourniquet for 30 - 120 seconds before injection of propofol ( pretreatment of lidocaine ) . Recently , propofol medium-chain triglyceride/long-chain triglyceride ( MCT/LCT ) emulsion was proposed for its ability to decrease pain on injection . The authors conducted a double-blind r and omized controlled trial to compare the incidence and severity of pain on injection between the new propofol MCT/LCT and the propofol LCT with and without lidocaine pretreatment . MATERIAL AND METHOD 360 adult patients with ASA physical status I-III who underwent general anesthesia were assigned into 4 groups by computer-generated r and omization ; Group I - pretreatment of lidocaine 1 % and propofol LCT Group I - pretreatment oflidocaine 1 % and propofol MCT/LCT Group III - pretreatment of saline and propofol MCT/LCT and Group IV- pretreatment of saline and propofol LCT mixed with lidocaine 1 % . All groups received pretreatment under tourniquet for 60 seconds . Evaluators who were blinded to the injected drugs recorded pain intensity ( none , mild , moderate and severe ) after the first 30 % of total induction dose ofpropofol was injected at a rate of 1 ml/s by question ing patients . Data was analyzed by using Kruskal-Wallis testfor ordinal data . Post hoc analysis was performed by using the Mann-Whitney U-test with Bonferroni 's correction on pairwise comparisons and was considered significant with p value of less than 0.05 . RESULTS Patients in an individual group had insignificant differences in their demographic data . The incidences of pain in Group I , II , III and IV were 61.1 % , 46.7 % , 62.2 % and 55.6 % respectively with an average incidence of 56 % ( p = 0.006 ) . There were 15.6 % , 5.6 % , 23.3 % and 24.4 % of patients in Group I , II , III and IV who rated pain intensity as severe . Pain on injection of propofol MCT/LCT with lidocaine pretreatment was less than propofol MCT/LCT alone ( p = 0.001 ) . CONCLUSION The incidence of pain on injection of propofol MCT/LCT was not different from that caused by propofol LCT with pretreatment of lidocaine and the intensity of pain on propofol MCT/LCT injection decreased significantly when using lidocaine pretreatment . Therefore , the authors could conclude that an injection of new propofol MCT/LCT solution was an alternative in reducing pain sensation to propofol LCT with pretreatment of lidocaine . Additionally , pain of propofol MCT/LCT injection could be alleviated by pretreatment of lidocaine with a 60 seconds tourniquet time before the injection ofpropofol Purpose Propofol injection is known to cause distressing pain , and various methods have been used to decrease this pain . We investigated the efficacy of the lidocaine + metoclopramide and lidocaine + ketamine combinations on modulating propofol injection pain . Methods Ninety ASA I/II patients aged 20–60 years were r and omly assigned to three groups to receive lidocaine 20 mg ( group L ) , lidocaine 20 mg + metoclopramide 10 mg ( group LM ) , or lidocaine 20 mg + ketamine 5 mg ( group LK ) , respectively , with venous occlusion for 1 min using a forearm tourniquet . Propofol 0.5 mg/kg was subsequently administered into a dorsal h and vein , and pain was assessed during its injection using a verbal rating score . The results were analyzed statistically with analysis of variance , the chi-square test , and the Wilcoxon rank sum test , where appropriate . The significance level was set at p < 0.05 . Results The incidence of pain was rated to be significantly less in patients in groups LM ( 40 % ) and LK ( 6.7 % ) than in those in group L ( 83.3 % ) ( p = 0.001 and p < 0.001 , respectively ) . The pain score [ median ( range ) ] was also significantly less in patients in groups LM [ 0 ( 0–3 ) ] and LK [ 0 ( 0–2 ) ] than in those in group L [ 2 ( 0–3 ) ] ( p = 0.001 for both groups ) . Conclusion The lidocaine – ketamine combination is most effective for decreasing the pain on propofol injection Purpose Pain on propofol injection is a common adverse effect . This study examined the effect of a combination of nitroglycerin and lidocaine on pain during propofol injection compared to lidocaine alone . Methods In a double-blind , prospect i ve trial , 90 patients scheduled to undergo elective plastic surgery were allocated r and omly to three groups , to receive lidocaine 20 mg ( n = 30 ) , a combination of lidocaine 20 mg and nitroglycerin 0.1 μg/kg ( n = 30 ) , or normal saline as a placebo ( n = 30 ) , with venous occlusion for 1 min , followed by the administration of 25 % of the total calculated dose of propofol ( 2 mg/kg ) into a dorsal h and vein . The pain intensity during the propofol injection was assessed using a four-point scale ( 0 = none , 1 = mild , 2 = moderate , 3 = severe ) . Hemodynamic variables – mean arterial pressure and heart rate – were measured during the preoperative and intraoperative periods . Results A significantly higher proportion of patients in the placebo group ( 83 % ) experienced pain compared to the lidocaine and combination groups ( 43 and 7 % , respectively ; both , P < 0.01 ) . The incidence of pain in the combination group was lower than that in the lidocaine group ( P < 0.01 ) . The pain score ( median ) was lower in the lidocaine ( 0 ) and combination ( 0 ) groups than in the placebo group ( 2 ) ; ( P < 0.01 ) . The hemodynamic variables were similar in the three groups . Conclusion A combination of nitroglycerin 0.1 μg/kg and lidocaine 20 mg with venous occlusion for 1 min was more effective than lidocaine 20 mg alone in decreasing pain during propofol injection Objective Pretreatment with intravenous 40 mg or 0.5 mg/kg lidocaine with venous occlusion is recommended to prevent pain following injection of lipid emulsion propofol . This approach is not sufficient to prevent pain from the injection of microemulsion propofol . The present study investigated whether a higher dose of lidocaine pretreatment with venous occlusion would be more effective for reducing pain following injection of microemulsion propofol compared with 40 mg lidocaine . Methods Patients undergoing elective surgery were r and omly assigned to one of three groups : pretreatment with 40 mg ( group L40 ) , 60 mg ( group L60 ) or 80 mg ( group L80 ) lidocaine intravenously with venous occlusion , followed by injection with microemulsion propofol 1 min later . Pain was assessed on a four-point scale ( severe , moderate , mild , none ) based on physical responses to the injection . Results A total of 68 patients were included in the final analysis . Pain severity and incidence were significantly lower in patients in group L60 and L80 compared with patients in group L40 . There were no statistically significant differences in pain incidence or severity between group L60 and group L80 . Conclusions Pretreatment with 60 mg lidocaine intravenously with venous occlusion may be the most effective minimum dose for reducing injection pain following microemulsion propofol administration for induction of anaesthesia Background and objectives : This prospect i ve , double‐blind , r and omized , placebo‐controlled study was design ed to determine the efficacy of dexmedetomidine compared with lidocaine in reducing the pain of propofol and rocuronium injection pain . Methods : One hundred and fifty patients , scheduled for elective surgery with general anaesthesia , were divided into five groups : saline ( Group 1 ) , dexmedetomidine 0.25 & mgr;g kg−1 ( Group 2 ) , lidocaine 0.5 mg kg−1 ( Group 3 ) , dexmedetomidine 0.25 & mgr;g kg−1 plus lidocaine 0.25 mg kg−1 ( Group 4 ) or dexmedetomidine 0.25 & mgr;g kg−1 plus lidocaine 0.5 mg kg−1 ( Group 5 ) were administered at a rate of 0.5 mL s−1 after tourniquet application . The occlusion was released after 1 min and 5 mL of propofol was injected over 20 s. Pain was evaluated by use of a 10‐point verbal analogue scale . Then , the rest of the induction dose of propofol , 3 mL of saline bolus and 0.6 mg kg−1 of rocuronium , was injected . The response to injection of rocuronium was assessed with a four‐point scale ( 0–3 ) . Results : Groups 1 and 2 were found to have higher propofol injection pain scores than Groups 3 , 4 and 5 ( P < 0.05 ) . When the study groups were compared according to the overall incidence of withdrawal movements due to rocuronium ( ⩾1 response ) in Groups 1 , 2 , 3 , 4 and 5 , they were different ( 86.7 % , 60 % , 36.7 % , 50 % and 40 % , respectively ) ( P < 0.05 ) . Except Group 1 , there was no significant difference between the groups according to incidence of withdrawal movement after rocuronium injection ( P = 0.325 ) . Conclusions : Pretreatment with dexmedetomidine is not effective in reducing injection pain of propofol , but may attenuate the h and withdrawal associated to rocuronium , as lidocaine does Abstract Purpose . The effects of nonsteroidal antiinflammatory drugs ( NSAIDs ) on pain from propofol injection are controversial , partially because NSAIDs themselves cause injection pain . We evaluated the effects of flurbiprofen axetil ( LFP ) , a prodrug of an NSAID , on pain induced by intravenous propofol injection , because LFP produces little pain on injection . Methods . A r and omized , double-blind , controlled trial was undertaken in patients who were assigned to one of three groups ( n = 50 in each ) . Patients received either 5 ml of saline followed approximately 10 min later by propofol mixed with 0.4 ml of saline , LFP ( 50 mg , 5 ml ) i.v . followed by propofol mixed with 0.4 ml of saline , or 5 ml of saline followed by propofol mixed with lidocaine ( 40 mg , 0.4 ml ) . Verbal rating scores for injection pain were assessed every 10 s during propofol administration at a rate of 0.05 mg·kg−1·s−1 . Results . None of the patients complained of pain during injection of LFP or saline . Admixture of lidocaine , but not of LFP , significantly reduced the incidence of pain and the severity of pain scores during propofol injection ( P = 0.0017 and P < 0.001 , respectively ) . Conclusion . Lidocaine , but not LFP , is effective for controlling pain induced by propofol injection . This result suggests that NSAIDs have little effect on pain from propofol injection BACKGROUND AND OBJECTIVES Performed a r and omized , double blind study to assess the efficacy of intravenous ( IV ) pretreatment with lidocaine , IV paracetamol ( Perfalgan ) or lidocaine mixed with fentanyl in reducing propofol injection pain . METHODS Immediately after venous occlusion with a rubber tourniquet on the patient 's arm IV lidocaine 1 % 4 mL ( Group L , n = 50 ) , IV paracetamol ( Perfalgan ) 4 mL ( 40 mg ) ( Group R , n = 50 ) , lidocaine 2 % mixed with 100 microg fentanyl ( Group LF , n = 50 ) or normal saline 4 mL ( Group P , n = 50 ; as placebo control ) was given to 200 adult patients . The release of the venous occlusion was done after 60s and followed by intravenous administration of propofol 2.5 mg kg(-1 ) at rate of 0.5 mg s(-1 ) through a 20 G catheter inserted in h and dorsum vein . Pain assessment was made during the propofol injection . This included movement of h and , spontaneous verbal expressions of pain , frowning , and moaning during the injection of propofol . RESULTS Lidocaine-fentanyl ( 70 % pain free ) , and lidocaine ( 68 % pain free ) significantly reduced propofol injection pain more than paracetamol ( 54 % pain free ) and more than placebo ( 36 % pain free ) ( p < 0.05 ) . The difference in reducing the incidence of propofol injection pain between lidocaine and lidocaine-fentanyl did not reach statistical significance . There was a significant superiority of paracetamol compared to placebo ( p < 0.05 ) . CONCLUSIONS Propofol , a commonly used anesthetic . Given as a venous retention pretreatment 60 seconds before propofol , lidocaine and lidocaine-fentanyl were found to significantly reduce the propofol injection pain , whereas IV paracetamol ( Perfalgan ) slightly reduced the propofol injection pain OBJECTIVES Propofol causes considerable pain upon injection , although different methods and propofol formulations have been used to decrease this pain . We aim ed to investigate the effect of i.v . esmolol pretreatment on propofol injection pain . METHODS Ninety ASA I-II patients undergoing elective surgery under general anesthesia were r and omly assigned into three groups of thirty each . A 20 G cannula was inserted into the dorsum of the nondependent h and . After venous occlusion for one minute , groups E , L and S were pretreated with 5 mg/ml ( total 2 ml ) esmolol , 40 mg lidocaine and 2 ml saline i.v . respectively . After release of venous occlusion , one fourth of the total propofol dose was administered at a rate of 0.5 ml/sec . During the injection of both pretreatment solution and propofol , patient pain was assessed by using 4 point scale . Heart rate and noninvasive arterial blood pressure values were recorded before induction , just after entubation and five minutes after entubation . RESULTS Demographic values were similar among groups . Incidence of pain on injection of propofol in the control , esmolol and lidocaine groups was 90 % , 33.3 % , 50 % respectively ( p<0.05 ) . Heart rate , systolic arterial pressure , and diastolic arterial pressure values were not different between the groups . CONCLUSION Pretreatment with low dose esmolol i.v . Seems to be effective in attenuating pain during propofol injection Abstract Objective : Pain on injection is a well known adverse effect of propofol . The purpose of this study was to compare the analgesic effect of a lidocaine (lignocaine)/remifentanil combination compared with either lidocaine alone or remifentanil alone during propofol injection for induction of anaesthesia . Methods : In a r and omised , double-blind , prospect i ve trial , 129 patients were allocated to one of three groups ( each n = 43 ) receiving lidocaine 20 mg , remifentanil 0.3 μg/kg or lidocaine 20 mg plus remifentanil 0.3 μg/kg as pretreatment , followed by injection of 5mL of 1 % propofol . Pain severity was evaluated on a four-point scale . Results : Two patients ( 4.7 % ) complained of pain in the lidocaine plus remifentanil group compared with 15 ( 35.7 % ) in the lidocaine alone group and 18 ( 42.9 % ) in the remifentanil alone group ( p < 0.001 ) . There was no significant difference in the incidence of injection pain between the lidocaine alone and remifentanil alone groups ( p = 0.21 ) . Conclusion : Pretreatment with a combination of lidocaine and remifentanil is more effective than either pretreatment alone in reducing pain on injection of propofol Background : Propofol causes a high incidence of pain during intravenous ( IV ) injection . The aim of this r and omized , placebo-controlled , double-blinded study was to determine whether pre-treatment with IV ramosetron , used for prophylaxis of postoperative nausea and vomiting ( PONV ) , would reduce propofol-induced pain as an equivalent to lidocaine . Material s and Methods : Hundred and twenty American Society of Anesthesiologists grade ( ASA ) I and II patients were r and omly assigned into three groups ( 40 in each ) . Group N received 2 ml of 0.9 % saline , Group L received 2 ml of lidocaine , and Group R received 2 ml of ramosetron . Mid forearm was occluded manually before injection and released after 1 min and then propofol was injected over 5 s. Patients were observed and question ed 15 s later if they had pain in the arm and pain was scored on a four-point scale : 0 = no pain , 1 = mild pain , 2 = moderate pain , and 3 = severe pain . Unpaired Student 's t-test and chi-square test/Fisher ’ exact test were used to analyze results . Results : The incidence of pain in groups N , L , and R were 65 , 35 , and 30 % , respectively . Pain was reduced significantly in the groups L and R ( P < 0.05 ) . Two patients each in Groups L and R ( 5 % each ) had moderate and severe pain . This difference in pain was statistically insignificant , but when compared to Group N ( 25 and 30 % , respectively ) it was statistically significant . Conclusion : Pretreatment with ramosetron 0.3 mg and lidocaine 40 mg are equally effective in preventing pain from propofol injection BACKGROUND Paediatric procedural sedation using propofol has been shown to be safe and effective and is widely used . Pain at the injection site is a frequent complaint and can be particularly distressing for children , especially for those undergoing repeated procedures . Ketamine has analgesic properties and can diminish the incidence of propofol infusion pain in adults . The aim of the study was to investigate whether pretreatment with ketamine would reduce infusion line pain in propofol sedation in children . METHODS We performed a prospect i ve , r and omized , double-blind trial in a paediatric sedation unit of a tertiary referral teaching hospital . A total of 122 children admitted for gastroscopy were r and omly allocated into two groups . Group 1 received atropine and ketamine before propofol infusion . Group 2 received atropine , normal saline solution , and a mixture of propofol with lidocaine . The main outcome measure evaluated was pain associated with the infusion and secondary outcome measures were mean medium arterial pressure decrease and desaturation . RESULTS The incidence of pain of the infusion was significantly lower in patients pretreated with ketamine ( 8 % vs 37 % , P = 0.0001 ) . CONCLUSIONS Pretreatment with ketamine ( 0.5 mg.kg-1 ) is very effective in preventing propofol infusion pain Background / Aims Propofol has been used in the past for sedation in upper gastrointestinal ( GI ) endoscopic procedures . This study aim ed to measure the incidence of propofol injection pain and evaluate the effect of lidocaine on pain caused during sedative upper GI endoscopic examinations . Methods Subjects scheduled to undergo sedative diagnostic upper GI endoscopy were r and omly assigned to lidocaine and placebo groups . Pretreatment with a bolus of 1 % lidocaine 2 ml or normal saline 2 ml into the largest dorsal vein of the non-dominant h and was followed by propofol administration . Pain intensity was estimated by an examiner blinded to the group assignment using a four-point verbal rating scale . A score of 1–3 was regarded as pain . Results A total of 121 patients ( males , 69 ; age , 58.6 ± 12.1 years ) completed the study ; 61 and 60 subjects were r and omly assigned to the lidocaine and placebo groups , respectively . The incidence of pain during upper GI endoscopy was 60 % . The lidocaine group showed a lower incidence of pain than the placebo group ( 37.7 % vs. 60.0 % , P = 0.018 ) . The lidocaine group perceived significantly less pain than the placebo group ( median pain score , 0 vs. 1 , P = 0.008 ) . Only lidocaine pretreatment was an independently associated factor against pain perception ( OR , 0.380 ; 95 % CI , 0.177–0.815 ; P = 0.013 ) . Conclusions Pretreatment using lidocaine was found to be effective in reducing propofol injection-induced pain . However , its usefulness for GI endoscopic procedures in daily clinical practice needs further evaluation because of the low intensity of pain Propofol causes pain on intravenous injection in 28 to 90 % of patients . A number of techniques have been tried to minimize propofol-induced pain , with variable results . In a r and omized , double-blind , placebo-controlled trial , we compared the efficacy of ephedrine 30 μg/kg pretreatment to lignocaine 40 mg for prevention of propofol-induced pain . Ninety-three adult patients , ASA 1 and 2 , undergoing elective laparoscopic cholecystectomy were r and omly assigned to three groups of 31 each . Group 1 received normal saline , group 2 received lignocaine 2 % ( 40 mg ) and group 3 received 30 μg/kg ephedrine . All pretreatment drugs were made up to 2 ml . Pain at the time of propofol injection was assessed on a four-point scale : 0=no pain , 1=mild pain , 2=moderate pain , and 3=severe pain . Twenty-seven patients ( 87 % ) of ephedrine pretreatment patients had pain during intravenous injection of propofol as compared to 24 ( 77 % ) in the normal saline group . In the lignocaine group , propofol-induced pain was observed in only 13 ( 42 % ) when compared with other study groups ( P<0.05 ) . Pretreatment with ephedrine 30 μg/kg did not attenuate pain associated with intravenous injection of propofol , nor did it improve haemodynamic stability during induction . However , pretreatment with 2 % lignocaine ( 40 mg ) was effective in attenuating propofol-associated pain Abstract Objective : Pain on injection is still a major problem with propofol . Lignocaine ( lidocaine ) is effective in preventing propofol-induced pain on injection , but can not entirely control the pain . The purpose of this study was to examine the effect of lignocaine plus ketamine , an N-methyl-D-aspartate receptor antagonist , on pain on injection of propofol . Design : Prospect i ve , r and omised , double-blind , placebo-controlled study . Setting : University Hospital . Patients : 120 female patients scheduled for gynaecological laparoscopy . Interventions : Patients received intravenously lignocaine 20 mg plus either placebo ( saline ) or ketamine at three different doses ( 2.5 mg , 5 mg and 10 mg ) , with manual venous occlusion for 1 minute , followed by administration of propofol 0.5 mg/kg into a dorsal h and vein ( n = 30 in each group ) . A blinded research er asked the patients to assess pain during the propofol injection . Main outcomes measures and results : Twelve of 30 patients ( 40 % ) complained of pain in the lignocaine/placebo group compared with three ( 10 % ) in the lignocaine/ketamine 5 mg group and three ( 10 % ) in the lignocaine/ketamine 10 mg group ( both p = 0.015 ) . No significant differences were found between the lignocaine/ketamine 2.5 mg ( 10 patients [ 33 % ] ) and lignocaine/placebo groups . No complications such as pain , oedema , wheal or flare response were observed at injection sites within the first 24 hours after anaesthesia . Conclusion : Combined lignocaine 20 mg and ketamine 5 mg , with manual venous occlusion , is more effective than lignocaine 20 mg alone for pain control during propofol injection BACKGROUND Pain on injection is a common adverse effect with propofol used for general anesthesia . OBJECTIVES The aims of this study were to evaluate the analgesic effect of dexamethasone during propofol injection and investigate whether a combination of dexamethasone and lidocaine produced additional analgesic efficacy compared with either treatment alone . METHODS In a double-blind , prospect i ve trial , patients scheduled to undergo elective plastic surgery were r and omized to receive lidocaine 20 mg , dexamethasone 6 mg , combination lidocaine 20 mg and dexamethasone 6 mg , or normal saline with venous occlusion for 1 minute , followed by administration of 25 % of the total calculated dose of propofol ( 2.5 mg/kg ) into a dorsal h and vein . Pain intensity and incidence were evaluated during a 10-second pause before the induction of anesthesia , using a 4-point verbal rating scale ( 0=none , 1=mild , 2=moderate , 3=severe ) ; a score of 1 to 3 was counted as pain . Patients were monitored hourly for 24 hours postsurgery by a blinded investigator for adverse effects at the injection site ( eg , pain , edema , wheal , flare response ) . RESULTS A total of 140 ( 35 per group ) Korean patients ( 91 women , 49 men ; mean [ SD ] age , 47 [ 14 ] years ; mean [ SD ] height , 162 [ 8 ] cm ; and mean [ SD ] body weight , 60 [ 8 ] kg ) completed the study . Demographic variables were similar among groups . With respect to pain intensity , mean pain score was significantly less in the combination group than in the lidocaine or dexamethasone groups ( P<0.01 , respectively ) , although the median pain scores for all groups were 0 . The incidence of pain associated with propofol injection was reduced significantly in the combination group compared with the lidocaine or dexamethasone group ( 0 % vs 34.3 % and 37.1 % , respectively ; both , P<0.01 ) . One patient ( in the combination group ) complained of perineal itching immediately following injection ; however , this subsided within a few seconds and did not require any intervention . No other adverse effects at the injection site were observed in any patient in the 24 hours post surgery . CONCLUSION Combination lidocaine 20 mg and dexamethasone 6 mg , with venous occlusion for 1 minute , was more effective than lidocaine 20 mg or dexamethasone 6 mg alone for pain control during propofol injection in these Korean patients Propofol is one of the most frequently applied intravenous anesthetics for the induction of general anesthesia . However , pain on injection of this agent is a considerable problem in daily anesthesia practice because of its severity . Administration of lidocaine prior to propofol injection is a st and ard technique for reducing the pain on injection . However , this method provides insufficient pain relief . To evaluate whether pretreatment with an ultra-short acting barbiturate , thiopental , is more effective than with lidocaine , a r and omized and single-blinded trial was conducted . Patients ( 20 - 65 years old , n = 137 ) were allocated into six groups , and applied with physiological saline , thiopental ( 25 , 50 , 75 , or 100 mg ) , or lidocaine ( 40 mg ) at 30 second prior to propofol injection ( 1 mg/kg , 1200 ml/h ) . The patient was interviewed about the degree of pain just after propofol was totally injected . Both thiopental ( > or = 25 mg ) and lidocaine decreased the severity of pain in comparison with physiological saline as evaluated by a six- grade d pain score . Lidocaine failed to influence the incidence of pain ( from 86 % to 55 % ) , although thiopental significantly decreased it to 40 % ( 25 mg ) , 21 % ( 50 mg ) , 12 % ( 50 mg ) , and 0 % ( 100 mg ) , respectively . Thiopental ( > or = 50 mg ) decreased both the severity and incidence of pain more effectively than lidocaine . A Hill plot analysis of these data , after rearrangement by patient 's body weight , estimated that the half-effective dose ( ED50 ) and the ED99 of this drug to block pain on injection of propofol were 0.6 and 1.4 mg/kg , respectively Objective Pain is a well recognised complication of propofol injection . The purpose of this study was to compare the efficacy of flurbiprofen , lidocaine and a combination of the two in reducing pain on injection of propofol . Design Prospect i ve , r and omised , double-blind , placebo-controlled study . Setting University hospital in Tsukuba City , Japan . Patients and interventions 120 patients , 56 males and 64 females , aged 20–66 years , scheduled for elective plastic surgery were included . Patients received intravenously either lidocaine 20 mg , flurbiprofen 50 mg , both , or placebo ( saline ) accompanied by manual venous occlusion for 2 minutes , followed by administration of propofol 2 mg/kg into a dorsal h and vein ( n = 30 in each group ) . A blinded research er asked each patient to evaluate the pain score ( 0 = none , 1 = mild , 2 = moderate , 3 = severe ) during propofol injection . Main outcome measures and results The incidence and intensity of pain was less in patients receiving lidocaine ( 27 % , pain score 0 [ median ] ) , flurbiprofen ( 43 % , 0 ) , or both ( 3 % , 0 ) along with venous occlusion than in those receiving placebo ( 90 % , 2 ) along with venous occlusion ( p < 0.01 ) . Combined lidocaine and flurbiprofen with venous occlusion was the most effective treatment ( p < 0.05 ) . No complications such as pain , oedema , wheal or flare response were observed at the injection sites within the first 24 hours after surgery . Conclusion Combined lidocaine 20 mg and flurbiprofen 50 mg along with venous occlusion for 2 minutes was very effective for reducing pain on injection of propofol in patients scheduled for elective plastic surgery Purpose Since the introduction of propofol , several drugs and methods have been used to alleviate the pain on its injection . This study was design ed to evaluate the effect of adding sevoflurane 3 % during preoxygenation in alleviation of pain on propofol injection . Methods In this r and omized single-blinded study , 100 patients were r and omly allocated equally into five groups : sevoflurane – lidocaine – tourniquet ( SLT ) , sevoflurane – lidocaine ( SL ) , lidocaine – tourniquet ( LT ) , lidocaine ( L ) , and sevoflurane ( S ) . Approximately 10 min before the induction of anesthesia , midazolam 1–2 mg was administered intravenously to all patients . All patients received fentanyl 1 µg/kg as pretreatment and a full induction dose of propofol . A blinded anesthesia nurse assessed pain and h and movements throughout the injection of propofol . Results In the SLT group , all patients ( 100 % ) were pain free and had no h and movements . There was no significant difference in pain grade or in h and movements between the L and the S groups , or between the SLT and the SL groups . However , significant differences were observed in pain grade between the SLT and the L groups as well as between the SLT and the S groups . In addition , a significant difference in h and movement was observed only between the SLT and the S groups . Conclusion The addition of 3 % sevoflurane at the time of preoxygenation for 1 min along with routine use of lidocaine – tourniquet completely prevented pain upon propofol injection , whereas sevoflurane by itself provided similar analgesia to premixed lidocaine with propofol Eight modes of administration of propofol were assessed in order to minimise the pain of injection . An intravenous bolus injection in the antecubital fossa was the only approach that caused no pain . When administered intravenously in the dorsum of the h and the pain score and the number of patients who experienced pain was reduced significantly by mixing the agent with lignocaine when compared with a bolus injection . Slowing the speed of injection caused the greatest discomfort . An indirect biochemical mechanism for the pain is proposed Background and objective : The incidence of pain associated with the injection of propofol still remains a problem . This study sought to examine the analgesic effects of inhaled nitrous oxide in oxygen on the prevention of propofol injection pain . Methods : Nitrous oxide in oxygen was compared with a lidocaine ( 20 mg)-propofol mixture and with propofol alone ( control ) in a prospect i ve , r and omized , observer-blinded study . ASA I and II patients ( n = 135 ) scheduled for elective surgical procedures were studied . A st and ard propofol injection technique and scoring system to measure the pain on injection was used . Results : Demographic variables were similar between the study groups . Without analgesia ( control ) 26 of 45 patients ( 58 % ) reported pain on injection compared with 11 of 45 patients ( 24 % ) in both the nitrous oxide ( 95 % CI : 14 - 52 % , P = 0.001 ) and lidocaine groups ( 95 % CI : 14 - 52 % , P = 0.001 ) . Conclusions : The inhalation of a nitrous oxide/oxygen mixture significantly reduces the incidence of pain during propofol injection . This therapeutic stratagem was as effective as a lidocaine-propofol mixture The effect of pretreatment with alfentanil 10 ( Alf10 ) , 15 ( Alf15 ) or 20 ( Alf20 ) μ ˙ kg‐1 on reducing injection pain caused by propofol was compared with lignocaine 10 mg mixed with propofol ( Lign ) . This double‐blind , double‐dummy and r and omized study included 100 children with a mean age of 4.3 ± 0.6 years , 25 children in each group , undergoing minor otolaryngological surgery . The children were premedicated orally with midazolam 0.5 mg ˙ kg‐1 and atropine 0.03 mg ˙ kg‐1 . Injection pain occurred in 4 % in the Lign group . The corresponding figures were 40 , 16 and 20 % in the Alf10 , Alf15 and Alf20 groups , respectively . Both 1 % lignocaine 10 mg and alfentanil 15 μg ˙ kg‐1reduced injection pain significantly compared with alfentanil 10 μ ˙kg‐1.Pretreatment with alfentanil significantly diminished haemodynamic responses to tracheal intubation . Furthermore , the concomitant use of alfentanil and propofol caused transient severe bradycardia and a significant decrease in heart rate after laryngoscopy We have conducted a r and omized , double-blind study in 255 ASA I and II patients to compare the efficacy of lignocaine and metoclopramide in minimizing the pain of injection of i.v . propofol . When administered immediately before propofol into a dorsal h and vein , compared with placebo both drugs significantly reduced the incidence of pain on subsequent injection of propofol ( P < 0.001 ) . Twenty patients who had received metoclopramide ( n = 85 ) experienced pain , compared with 18 who had received lignocaine ( n = 85 ) and 42 who had been pretreated with saline ( n = 85 ) STUDY OBJECTIVE To investigate whether methylene blue , given before injection of propofol , was effective in reducing the frequency and severity of pain associated with propofol injection . DESIGN Prospect i ve , r and omized , double-blinded clinical study . SETTING Operating room of a university hospital . PATIENTS 90 adult , ASA physical status 1 and 2 patients undergoing elective surgery . INTERVENTIONS Patients were r and omly allocated to one of three groups of 30 patients each . Group I received 50 mg of methylene blue , Group II received 40 mg of lidocaine , and Group III , the control group , was given normal saline . All drugs were given as a 2.0 mL bolus 45 seconds before propofol administration . MEASUREMENTS Injection pain using vocal responses , facial grimacing , arm withdrawal , tears , and question ing of the patient were noted . A 4-point scale was used for documenting pain . MAIN RESULTS Pain frequency was 90 % in the saline group , whereas the frequencies were significantly lower in the lidocaine and methylene blue groups ( 26.7 % and 40 % , respectively ) . CONCLUSIONS Intravenous pretreatment with methylene blue appears to be effective in reducing the pain during propofol injection We performed a r and omized , placebo-controlled , double-blind study to compare the efficacy of intravenous ( IV ) lidocaine and topical nitroglycerin ointment in preventing pain during propofol injection . Nitroglycerin or placebo ointments were applied to the back of the h and over the skin area overlying the IV catheter tip ; lidocaine was or was not added to the propofol solution . One hundred twenty-four patients were r and omly assigned to receive one of four treatments : placebo and plain propofol , propofol mixed with lidocaine , nitroglycerin ointment and plain propofol , and nitroglycerin ointment and propofol mixed with lidocaine . Hence , there were 31 patients in each treatment group . Patients receiving nitroglycerin ointment and plain propofol had the highest incidence of pain on propofol injection ( 23 of 31 patients , 74 % ) , and the highest median pain score . Only when lidocaine was added to propofol did it effectively reduce the incidence and severity of pain . Patients aged 50 yr and older had a significantly lower incidence and less severe pain . We conclude that lidocaine and age , but not topical nitroglycerin ointment , are factors associated with a decreased incidence of propofol-induced pain . ( Anesth Analg 1997;84:865 - 9 A r and omized double-blind study compared two methods of preventing the pain from injection of propofol , lignocaine pre-treatment followed by propofol and lignocaine added to propofol . One hundred patients received a 4 ml solution intravenously with a venous tourniquet for 1 minute , followed by propofol mixed with 2 ml of solution . Patients were divided into two treatment groups of 50 patients each : 4 ml 1 % lignocaine pre-treatment followed by propofol and 2 ml saline , or 4 ml saline followed by propofol and 2 ml 2 % lignocaine . Pain was assessed with a 100 mm visual analogue scale after induction and in recovery . The incidence of injection pain was 8 % in the propofol mixed with lignocaine group , and 28 % in the lignocaine pre-treatment group . This difference is statistically significant ( P=0.017 ) . For those patients who had pain , the mean pain score was 26.5 on induction for the propofol with lignocaine group ( n=4 ) , while the mean score was 44.4 for the pre-treatment group ( n=13 ) . The difference was not statistically significant ( P=0.25 ) . None of the propofol mixed with lignocaine group recalled pain , while 13 of the pre-treatment group did so . Lignocaine pre-treatment does not improve the immediate or the recalled comfort of patients during propofol induction when compared to lignocaine added to propofol . It is recommended that lignocaine should be added to propofol for induction rather than given before induction Objective : Findings from studies investigating optimal techniques for attenuating propofol-related injection pain are inconsistent . In previous studies , lidocaine pretreatment using a tourniquet has been reported to be superior , inferior , or equivalent to a lidocaine-propofol admixture for reducing pain . This discordance could represent either no meaningful difference in the treatments or underlying method ological differences in the previous studies . We hypothesized that tourniquet-controlled pretreatment with lidocaine would be superior to lidocaine-propofol admixture for reducing propofol injection pain . Methods : This r and omized controlled trial compared 3 groups-a control group ( saline pretreatment/saline admixture ; n = 50 ) , a pretreatment group ( lidocaine pretreatment/saline admixture ; n = 51 ) , and an admixture group ( saline pretreatment/lidocaine admixture ; n = 50 ) . The primary outcome was verbal pain score after injection . The incidence of pain on injection was explored as a secondary outcome . Results : The median ( interquartile range ) verbal pain score after study solution injection were as follows-control group : 3 ( 0 - 6 ) , pretreatment group : 0 ( 0 - 0 ) , and admixture group : 0 ( 0 - 2 ) . The pretreatment group had significantly lower pain scores when compared with the admixture group ( P = 0.016 ) , and both groups were superior to the control group . The pretreatment group had fewer subjects experiencing any injection pain than did the admixture group ( 20 % vs. 44 % , respectively ; P = 0.024 ) . Conclusions : Tourniquet-controlled pretreatment with lidocaine is statistically superior to admixing lidocaine with propofol for reducing propofol injection pain intensity , but the clinical importance of this small effect is question able . However , pretreatment more effectively eliminates injection pain BACKGROUND Pain on injection is a recognized adverse effect of propofol , an agent used to induce general anesthesia in surgical patients . Pretreatment with fentanyl has been reported to be effective in reducing propofol-induced pain . OBJECTIVE The aim of this study was to compare the efficacy of intravenous pretreatment with fentanyl 50 microg , fentanyl 100 microg , and lidocaine 40 mg , preceded by venous occlusion , for reducing pain on injection of propofol in adult Japanese surgical patients . METHODS This was a prospect i ve , r and omized , double-blind , placebo-controlled study . Adult Japanese surgical patients were r and omized to 1 of 4 groups to receive intravenous fentanyl 50 microg , fentanyl 100 microg , lidocaine 40 mg , or placebo ( 0.9 % isotonic saline ) . The drug administration was preceded by manual venous occlusion with a rubber tourniquet for 1 minute , followed by administering propofol 0.5 mg/kg injected into the largest dorsal vein of the h and through a 20-gauge intravenous cannula at the rate of 10 mg/sec . Pain on injection of propofol was assessed by an investigator who was blinded to group assignment . Patients were interviewed to assess pain intensity on injection using a 4-point verbal rating scale ( 0 = none ; 1 = mild ; 2 = moderate ; and 3 = severe ) . Incidence and severity of pain were determined in each of the 4 study groups . Adverse events related to the study drug were recorded before the induction of anesthesia and after surgery . Patients were monitored for adverse events for 24 hours following surgery . RESULTS A total of 120 patients ( 70 men and 50 women ; mean [ SD ] age , 44 [ 11 ] years ; height , 160 [ 7 ] cm ; weight , 56 [ 10 ] kg ) completed the study . Each group comprised 30 patients . No significant between-group differences in demographic characteristics were found . The overall incidence of propofol-induced pain was 77 % ( 23/30 patients ) with fentanyl 50 microg ( P = NS ) , 37 % ( 11/30 patients ) with fentanyl 100 microg ( P = 0.001 ) , and 33 % ( 10/30 patients ) with lidocaine 40 mg ( P = 0.001 ) compared with 83 % ( 25/30 patients ) with placebo . The median pain score was lower in patients who received fentanyl 50 microg ( 1 ; P = NS ) , fentanyl 100 microg ( 0 ; P = 0.001 ) , or lidocaine 40 mg ( 0 ; P = 0.001 ) than in those who received placebo ( 2 ) . The incidence and severity of pain were significantly different between the fentanyl 50-microg and 100-microg groups ( incidence , P = 0.002 ; severity , P = 0.001 ) . However , there was no significant difference in the incidence and severity of such pain between the fentanyl 100-microg and lidocaine 40-mg groups . Both study drugs were well tolerated . CONCLUSIONS Preceded by venous occlusion for 1 minute , fentanyl 100 microg was not significantly different from lidocaine 40 mg in reducing pain during injection of propofol in these adult Japanese surgical patients . Fentanyl 50 microg was ineffective in reducing such pain compared with placebo BACKGROUND AND OBJECTIVES Tramadol and metoclopramide have a local anesthetic effect similar to lidocaine following intradermal injection . When metoclopramide was retained in the venous system for 1 minute , it was found to be as effective as lidocaine in reducing propofol injection pain . Using this metoclopramide model , the effects of tramadol in reducing pain on propofol injection was investigated . METHODS One hundred five patients were r and omly allocated to receive 50 mg tramadol ( group T ) , 60 mg lidocaine ( group L ) , or normal saline ( group NS ) as pretreatment to reduce pain on propofol injection . Following venous occlusion with a tourniquet ( 70 mm Hg ) , one of the drugs was intravenously administered . Venous retention of the drug was maintained for 1 minute . Immediately after the tourniquet release , intravenous injection of 100 mg propofol ( 10 mL ) at a rate of 0.5 mL/s followed . Pain assessment was made after each injection . RESULTS Transient minor injection pain and local skin reactions were significantly greater with tramadol than with lidocaine ( P < .05 ) . Both tramadol and lidocaine significantly reduced the incidence and intensity of propofol injection pain when compared with normal saline ( P < .05 ) . CONCLUSIONS Using -minute retention in veins , both tramadol and lidocaine significantly reduced propofol injection pain . A local anesthetic activity is postulated A single‐blind , r and omised , controlled study was undertaken to compare the efficacy of three methods of preventing pain during injection of propofol on induction of anaesthesia . Patients were allocated r and omly to receive unmodified propofol , propofol with 0.05 % lignocaine , propofol at 4 ° C and unmodified propofol preceded by 10 ml of 0.9 % saline at 4 ° C . Prior injection of cold saline reduced the incidence of pain and discomfort significantly ( 22 % ) compared with unmodified propofol ( 75 % ; p < 0.005 ) and was similar to that after cold propofol ( 33 % ) and propofol with lignocaine ( 44 % ) . There was no significant difference between the treatment groups To examine the physicochemical stability of combinations of propofol-lidocaine mixtures frequently used in clinical practice , we added lidocaine 5 , 10 , 20 , or 40 mg to commercially available 1 % propofol 20 mL. To assess chemical stability , propofol concentrations were determined by gas chromatography assay for 24 h after preparation of the mixture . In addition , scanning electron microscopy was used to determine the maximum detectable droplet size in r and omly selected fields . Macroscopically , separate , colorless layers were first seen at 3 and 24 h after the addition of 40 and 20 mg of lidocaine to propofol , respectively , whereas the mixture with 5 or 10 mg of lidocaine was macroscopically stable . Propofol concentrations in the mixture with 40 mg of lidocaine decreased linearly and significantly from 4 to 24 h after preparation , whereas those combined with other lidocaine doses were unchanged compared with baseline concentrations . Scanning electron microscopy showed that droplets with diameters ≥5 & mgr;m first appeared 30 min after the addition of 40 mg of lidocaine to propofol , and the emulsion droplets were enlarged in a time- and dose-dependent fashion . Our results indicate that the addition of lidocaine to propofol results in a coalescence of oil droplets , which finally proceeds to a visible separate layer . Depending on the dose of lidocaine and the duration between its preparation and administration , this combination may pose the risk of pulmonary embolism Background and objective : Propofol is an intravenous ( i.v . ) anaesthetic agent that possesses many of the qualities of an ideal anaesthetic agent . The most significant side‐effect associated with propofol is pain on injection . Despite optimal therapy , the incidence of pain on propofol injection remains a problem . This prospect i ve , r and omized , double blinded study evaluated the effect of three different treatment strategies in decreasing pain on propofol injection . Methods : We studied 102 adult , ASA I‐II patients , scheduled for elective surgical procedures . Combination of i.v . lidocaine and nitrous oxide ( N2O ) in oxygen ( O2 ) inhalation pre‐treatment was compared with either treatment alone in the prevention of pain on propofol injection . A st and ard propofol injection technique and scoring system , to measure the pain on injection was used . Results : Demographic variables were similar between the groups . The incidence of no pain on propofol injection was similar in the lidocaine and N2O groups ( 63.6 % vs. 57.5 % ) ( 95 % confidence interval ( CI ) : 0.17‐0.29 , P = 0.61 ) . Combination therapy was associated with a greater incidence of no pain on injection ( 84 % vs. 63.6 % ) ( 95 % CI : 0.06‐0.48 , P = 0.04 ) . Conclusion : Combination of i.v . lidocaine and N2O in O2 inhalation pre‐treatment is more effective than either treatment alone in decreasing pain on propofol injection A controlled , double‐blind study was performed to compare the prior administration of intravenous saline 4 ml ( n = 36 ) , lignocaine 20 mg ( n = 36 ) or thiopentone 100 mg ( n = 43 ) on the pain produced by intravenous injection of propofol . One hundred and fifteen ASA 1 or 2 patients scheduled for minor surgery were studied using a r and omised , double‐blind design . Thiopentone was more effective than lignocaine in reducing the incidence of propofol injection pain ( p < 0.03 ) AIM Propofol has a high incidence of pain on injection , particularly when a vein on the back of h and is used . Administration of lidocaine , either before or mixed with propofol remains the most widely used method to attenuate this pain . The use of opioids such as alfentanil and fentanyl has been found to decrease pain induced by propofol injection . The purpose of this study was to evaluate the effects of different doses of remifentanil and alfentanil in minimizing the pain caused by propofol . METHODS In this r and omized , double-blind , placebo-controlled study , healthy premedicated children between the age group of 5 - 12 years admitted for adenotonsillectomy were r and omly allocated to one of 6 treatment groups . Group I : remifentanil 0.25 microg kg(-1 ) ; Group II : remifentanil 0.50 microg kg(-1 ) ; Group III : alfentanil 15 microg kg(-1 ) ; Group IV : alfentanil 20 microg kg(-1 ) 60 s prior to propofol mixed with 1 mL of 0.9 % normal saline ; Group V : lidocaine 1 mL of 1 % ( 10 mg ) added to 100 mg of propofol and Group VI : normal saline . During the injection of propofol ( 3 mg kg(-1 ) ) pain perception was assessed with a four-point behavioural scale : none , mild , moderate , or severe . RESULTS There were 52 subjects in Group I , 51 in Group II , 49 in Group III , 52 in Group IV , 52 in Group V and 52 in Group VI ; 63.46 % of patients in Group I , 39.21 % in Group II , 38.77 % in Group III , 36.53 % in Group IV , 38.46 % in Group V and 84.61 % in Group VI experienced pain . Statistically , Groups II , III , IV and V were significantly better than placebo in the reduction of propofol pain ( P<0.0001 ) . Groups II , III and IV significantly reduced the pain in comparison with Group I ( P<0.001 ) . CONCLUSION Pretreatment with intravenous remifentanil 0.5 microg kg(-1 ) , alfentanil 15 microg kg(-1 ) and 20 microg kg(-1 ) were equally effective in reducing pain associated with propofol injection in children between the age group of 5 - 12 years In a r and omized , double-blind , prospect i ve trial we compared the efficacy of pre-treatment with nitrous oxide ( with or without premixed lignocaine in propofol ) for the prevention of propofol-induced pain . Ninety consecutive patients were recruited in the study and divided into three groups of 30 each , who received either 50 % nitrous oxide in oxygen along with lignocaine 40 mg mixed in 1 % propofol 20 ml ( Group NL ) , 50 % nitrous oxide in oxygen without lignocaine in propofol ( Group N ) , and 50 % oxygen in air with lignocaine mixed in propofol 40 mg ( Group L ) . Pain scores were grade d on a four point verbal rating scale ( 0–3 ) . Eighty-nine patients completed the study while one patient developed excitement , agitation and tremor during nitrous oxide in oxygen inhalation . Eleven patients ( 36.7 % ) complained of pain in the group L compared to 7 ( 23.3 % ) , and 1 ( 3.3 % ) , in groups N and NL respectively [ group NL vs group L ( P<0.001 ) and group NL vs N ( P<0.001 ) ] . There was no statistical difference observed between group N and group L. Inhalation of 50 % nitrous oxide reduces pain on propofol injection . The combination of 50 % nitrous oxide and lignocaine mixed with propofol was the most effective treatment The efficacy of lignocaine ( 1 % ) mixed with propofol in reducing pain on injection with propofol was studied in 40 children undergoing elective surgery in a double – blind , r and omized comparison with glucose ( 5 % ) . The pharmacokinetics of propofol in a single dose of 2.5 mg/kg was also studied in eight children participating in the same sfudy . Lignocaine ( 1 mg ) significantly reduced pain on injection compared to the control group ( P < 0.001 ) . The induction characteristics of propofol were not affected by the lignocaine , and no undesirable interaction was found between the two drugs . The first – stage elimination half – life ( tl/2|3 ) of propofol in children was shorter ( mean 9.3 3.8 ( s.d . ) min ) than the values found in adults . This pharmacokinetic alteration may have clinical significance following repeated administration or continuous infusion of propofol In a r and omised , double-blind study we compared the efficacy of continuous remifentanil infusion ( 0.25 microg x kg(-1 ) x min(-1 ) with 40 mg lidocaine and placebo in the prevention of injection pain due to intravenous propofol administration ( 1.5 - 2 mg x kg(-1 ) ) in 155 patients scheduled for elective surgery . Pain severity was evaluated using a four-point scale . The incidence of injection pain was 62 % in the placebo group and could be reduced significantly by using remifentanil ( 30 % ; p < 0.0015 ) or lidocaine ( 33 % ; p < 0.005 ) . Analysis of the pain scores showed a significant difference between remifentanil and placebo ( p < 0.00005 ) as well as between lidocaine and placebo ( p < 0.0002 ) . There was no significant difference between remifentanil and lidocaine . Remifentanil provided effective pain relief , comparable with lidocaine , and is an alternative as part of an intravenous anaesthesia regimen to using another concomitant drug Background Research suggests that young children experience an increased incidence and severity of discomfort during propofol infusion . Evaluations of varied interventions to reduce or eliminate this discomfort with adult subjects suggest that premedication with intravenously administered lidocaine ( 0.5 mg/kg ) offers the best overall effectiveness . Objective Because this regimen ’s efficacy in a pediatric population is undocumented , we conducted a r and omized , double-blind , placebo-controlled study to determine the effectiveness of intravenous lidocaine pretreatment to alleviate pain in pediatric subjects before propofol infusion . Methods Subjects ( aged 2–7 years ) scheduled for painless diagnostic procedures received either a saline placebo or 1 of 2 lidocaine doses before administering propofol . To capture the patient ’s baseline behavioral state , a trained observer administered the vali date d Face , Legs , Activity , Cry , Consolability Pain Assessment Scale before propofol infusion . During deep sedation induction , the sedating physician , a trained research assistant , and the patient ’s parent documented maximum distress using a 100-mm visual analog scale ( VAS ) . Results Ninety-one subjects participated . We found no difference in VAS pain scores between groups pretreated with lidocaine 0.25 mg/kg , lidocaine 0.5 mg/kg , and placebo . Statistical analysis also found no interrater differences between parents , physician , or observer VAS scores . Conclusions Our data do not support using lidocaine pretreatment to alleviate pain/discomfort in pediatric patients during propofol infusion Background and objective : Pain is often experienced when propofol is injected , and intravenous lidocaine is often effective in preventing such pain . We decided to determine whether metoprolol , given before the injection of propofol , is as effective as lidocaine in reducing the incidence and severity of the pain . Methods : Ninety patients scheduled for elective surgery under general anaesthesia were r and omly allocated to one of three groups to receive either metoprolol 2 mg , lidocaine 20 mg or saline 2 mL before any propofol was injected . Each patient was given one of these agents intravenously via a 20‐G cannula on the dorsum of the h and whilst the venous drainage was occluded manually , at the middle of the forearm , for 45 s. After the occlusion was released , propofol 2.0–2.5 mg kg−1 , at room temperature , was injected at 2mL ( 20 mg ) every 4s . Pain was assessed verbally and scored as none ( 0 ) , mild ( 1 ) or severe ( 2 ) . Results : The incidence of severe pain in the control group ( 56.7 % ) was significantly higher than in the metoprolol and lidocaine groups ( 16.6 and 10 % , respectively ) . The number of patients who were free of pain was significantly higher in those who had been given either metoprolol or lidocaine . Conclusions : Pretreatment with intravenous metoprolol was equally as effective as lidocaine in reducing the pain associated with propofol injection BACKGROUND Although the new formulation of lipid-free microemulsion propofol ( MP ) has some advantages over the lipid emulsion , it reportedly produces more injection pain than lipid-based propofol . Intravenous lidocaine with application of a rubber tourniquet before administration of propofol is considered to be the best method for reducing injection pain ; however , this technique is not perfect . OBJECTIVE The goal of this study was to evaluate the effect of different methods of tourniquet application and lidocaine administration on MP injection pain . METHODS This single-center , r and omized controlled clinical trial was conducted in 140 patients aged 18 to 65 years . Patients were r and omly divided into 4 groups ( n = 35 each ) . Group A received MP ( 2 mg/kg ) after lidocaine ( 0.6 mg/kg ) with a tourniquet with arm down ( venous engorgement ) ; group B received MP after lidocaine with a tourniquet with arm up ( venous gravity drainage ) ; group C received MP with a tourniquet with arm down ; and group D ( control group ) received MP only ( with no tourniquet ) . In groups A and C , the tourniquet was released after MP ; in group B , the tourniquet was released before MP . Injection pain was evaluated by using a verbal pain score ( VPS ) . The bispectral index , the time from the beginning of drug injection to the loss of eyelash reflex , and time to the lowest bispectral index value were recorded . RESULTS Group A showed significantly less incidence of pain than the control group when MP was injected . The mean VPS was significantly lower in groups A , B , and C than in group D ( the control group ) . The VPS of group A was significantly lower than that in group B. Other observed values were not significantly different . CONCLUSIONS We concluded that intravenous retention of lidocaine with the application of a rubber tourniquet under venous engorgement of the arm reduces the incidence and intensity of MP injection pain . CLINICAL TRIAL REGISTRY UMIN000010725 One hundred and fifty ASA 1 and 2 patients were r and omly allocated to receive pethidine 25 mg ( 1 ml ) , lignocaine Wing ( 1 ml ) or 0.9 % saline ( 1 ml ) on a double‐blind basis , as pretreatment to reduce pain on injection of propofol . Both active treatments were significantly better than placebo at preventing pain ( p<0.01 ) . Lignocaine was most effective in preventing pain in men ( p<0.05 ) whilst pethidine was more effective in women ( p<0.05 ) Objective To assess the effect of granisetron pretreatment in alleviating propofol injection pain . Study Design A r and omized , controlled , double-blind study , using venous retention with a tourniquet . Material s and Methods One hundred fifty adult patients were r and omly assigned to one of three groups : group 1 ( who received 5 mL of 0.9 % saline pretreatment ) , group 2 ( who received 5 mL lidocaine [ 40 mg in 0.9 % saline ] pretreatment ) , and group 3 ( who received 5 mL granisetron [ 2 mg in 0.9 % saline ] pretreatment ) . Injections were given in the largest vein on the dorsum of the h and . After 2 minutes , the tourniquet was released and one fourth of the total calculated dose of propofol ( 2.5 mg/kg body weight ) was administered and pain assessment was made . Results Lidocaine and granisetron significantly reduced the incidence and severity of propofol injection pain more than placebo ( P < 0.001 ) . The efficacy of granisetron in alleviating the pain on injection of propofol was no different from lidocaine . Conclusions Granisetron pretreatment may be used to reduce the incidence of pain on injection of propofol , an advantage added to the useful prevention of postoperative nausea and vomiting Propofol causes pain or discomfort on injection in 28%–90 % of patients . A number of techniques have been tried for minimizing propofol-induced pain with variable results . We compared the efficacy of butorphanol and lidocaine for prevention of propofol-induced pain . One-hundred-fifty ASA I – II adults , undergoing elective surgery were r and omly assigned into 3 groups of 50 each . GroupI(NS)receivednormalsaline , GroupII(L)received lidocaine 2 % ( 40 mg ) , and Group III ( B ) received butorphanol 2 mg . All patients received pretreatment solutions made in 2 mL with normal saline administered over 5 s. One min after pretreatment patients received one-fourth of the total calculated dose of propofol ( 2.5 mg/kg ) over 5 s. Assessment of pain with IV propofol was done by using a four-point scale : 0 = no pain , 1 = mild pain , 2 = moderate pain and 3 = severe pain at the time of propofol injection . In the control Group 39 ( 78 % ) patients had pain during propofol injection as compared to 21 ( 42 % ) and 10 ( 20 % ) in the lidocaine and butorphanol groups , respectively ( P < 0.05 ) . Butorphanol was the most effective . We therefore suggest the IV pretreatment with butorphanol 2 mg for attenuation of pain associated with propofol injection One hundred seventy-six patients ( ASA physical status I or II ) presenting for elective surgery were r and omly allocated into six study groups to compare the incidence of propofol-induced pain after pretreatment with different doses of ephedrine as compared with lidocaine . Patients in Group P ( n = 30 ) received saline placebo ; patients in Group L ( n = 30 ) received 2 % lidocaine 40 mg ; patients received ephedrine 30 & mgr;g/kg ( Group E30 , n = 28 ) , 70 & mgr;g/kg ( Group E70 , n = 30 ) , 110 & mgr;g/kg ( Group E110 , n = 30 ) , and 150 & mgr;g/kg ( Group E150 , n = 28 ) , respectively , followed 30 s later by propofol 2.5 mg/kg . A blinded anesthesiologist asked the patient to evaluate the pain score ( verbal rating scale and face pain scale ) . The incidence and intensity of pain was less in the lidocaine and ephedrine groups than in the placebo group ( P < 0.01 ) . Before tracheal intubation , the arterial blood pressure was decreased in the P and L groups , and after intubation , hemodynamics were increased in the E110 and E150 groups , respectively ( P < 0.05 ) . We concluded that pretreatment with a small dose of ephedrine ( 30 and 70 & mgr;g/kg ) reduced the incidence and intensity of propofol-induced pain with a lesser decrease in arterial blood pressure than from propofol alone in lidocaine pretreatment STUDY OBJECTIVE To compare the efficacy of 2 % lidocaine " timing " on alleviation of pain upon induction using propofol or etomi date . DESIGN Prospect i ve , r and omized , double-blinded study . SETTING Academic teaching hospital . PATIENTS 80 adult , ASA physical status I , II , and III patients scheduled for elective outpatient or inpatient surgery with an intravenous induction agent . INTERVENTIONS Patients were r and omly assigned to two groups . Group A received preemptive saline 4 mL and lidocaine 4 mL mixed with either propofol 20 mL ( n = 20 ) or etomi date 20 mL ( n = 20 ) . Group B received preemptive lidocaine 4 mL and saline 4 mL mixed with either propofol 20 mL ( n = 20 ) or etomi date 20 mL ( n = 20 ) . The 4 mL dose of preemptive drug dwelled for three minutes . MEASUREMENTS The induction drug mixture was injected over 60 seconds while the patient was assessed for pain using a 4-point scale ( 0 = no pain,1 = mild , 2 = moderate , and 3 = severe ) . MAIN RESULTS Mean induction pain scores were 1.0 ( SD = 0.89 ) for propofol and 0.9 ( SD = 0.90 ) for etomi date , representing mild induction pain . Mean induction pain scores were 0.93 ( SD = 0.92 ) for the simultaneous treatment groups and 0.98 ( SD = 0.87 ) for the preemptive treatment groups . The observed differences in pain scores between the techniques were not statistically ( P > 0.62 ) or clinical ly meaningful . CONCLUSIONS Alleviation and intensity of post-injection pain were not significantly influenced by the " timing " of administration of lidocaine 80 mg or by the specific induction drug . Pre-lidocaine and " simultaneous " lidocaine with either propofol or etomi date prevented severe pain in 95 % of patients A r and omised , controlled , single‐blind study was performed on 100 patients to investigate a new method of reducing pain on propofol injection . Aspiration of 2 ml of the patient 's blood into a syringe of propofol immediately before injection was compared with the addition of lignocaine 20 mg or normal saline 2 ml to the propofol before injection . The addition of blood was significantly more effective in reducing pain on injection than the addition qf ' saline ( p < 0.001 ) , but was not significantly more effective than the addition of lignocaine A common drawback of propofol is pain on injection and lignocaine is commonly mixed with propofol to reduce the incidence and severity of this pain . In this study we sought to draw a comparison between the effectiveness of propofol medium chain and long chain triglyceride ( MCT/LCT ) alone , propofol medium chain and long chain triglyceride ( MCT/LCT ) premixed with lignocaine , and propofol long chain triglyceride ( LCT ) premixed with lignocaine , in preventing propofol pain on injection . 300 patients were r and omly divided into three equal groups . Group A received propofol-MCT/LCT premixed with normal saline , Group B received propofol-MCT/LCT premixed with 20 mg lignocaine and Group C received propofol-LCT premixed with 20 mg lignocaine . The incidence of pain in Group A was 63 % compared to 15 % in Group B ( X2 = 48.242 , p < 0.001 ) , whereas in Group C the incidence of pain was 24 % compared to 63 % in Group A ( X2 = 30.247 , p < 0.001 ) . There was no significant difference in incidence of pain between Groups B and C ( X2 = 2.5 , p = 0.11 ) . To conclude , propofol MCT/LCT alone provides no advantage to reduce pain on injection in comparison to propofol MCT/LCT premixed with lignocaine and propofol LCT premixed with lignocaine . Also , there is no significant difference in pain on injection between propofol LCT and propofol MCT/LCT as soon as lignocaine is added Purpose To evaluate the incidence of pain on injection in children during anesthetic induction with a 3:1.2 volume admixture of 1 % propofol and 2.5 % thiopentone ( P/T ) compared to a 10:1 volume admixture of 1 % propofol and 2 % lidocaine ( P/L ) . Methods After Ethics Committee approval and informed written parental consent , 127 children , aged one to ten years were studied and r and omized into two groups ; Group P/L received an induction with 5 mg·kg−1 of 1 % propofol and 1 mg·kg−1 of lidocaine , Group P/T with 3 mg·kg−1 of 1 % propofol and 3 mg·kg−1 of 2.5 % thiopentone in a st and ardized fashion . A single , blinded observer scored pain behaviour defined as a motor response of the arm , a verbal complaint of pain , cry and /or one of three st and ardized facial expressions of pain . Results The incidence of pain was 14 % in the P/T group , compared to 35 % in the P/L group ( χ12 = 7.5,P = 0.006 ) . Motor response was the most frequent pain response in the P/L group ( 68 % ) . Conclusion The P/T admixture is a practical and efficacious alternative to P/L for reducing pain on induction in children . Further work to evaluate the optimum proportions and possible adverse effects of this admixture should be done . RésuméObjectifÉvaluer l’incidence de douleur pendant l’injection d’anesthésique d’induction chez les enfants avec un mélange de volume de 3:1,2 de propofol à 1 % et de thiopental à 2,5 % ( P/T ) comparé à un volume de 10:1 de propofol à 1 % et de lidocaïne à 2 % ( P/L ) . Méthode : L’approbation du Comité d’éthique et le consentement écrit des parents ont permis l’étude de 127 enfants , de un à dix ans , répartis en deux groupes . Ceux du groupe P/L ont reçu une induction avec 5 mg·kg−1 de propofol à 1 % et 1 mg·kg−1 de lidocaïne et ceux du groupe P/T , 3 mg·kg−1 de propofol à 1 % et 3 mg·kg−1 de thiopental à 2,5 % de façon normalisée . Un observateur objectif a noté le comportement face à la douleur , défini par une réponse motrice du bras , une plainte verbale , un cri et/ou une des trois expressions faciales de douleur reconnues . RésultatsL’incidence de la douleur a été de 14 % dans le groupe P/T et de 35 % dans le groupe P/L group ( χ12 = 7,5 , P = 0,006 ) . La réponse motrice a été la réaction la plus fréquente dans le groupe P/L group ( 68 % ) . Conclusion Le mélange de P/T constitue une solution de rechange pratique et efficace au mélange P/L pour la réduction de la douleur lors de l’induction de l’anesthésie chez les enfants . Il reste à évaluer les dosages optimaux et les effets indésirables possibles de ce mélange Although it is well-known that 2 % lidocaine has an effective action for preventing propofol-induced pain , it has been unclear whether or not lidocaine of the concentration below 2 % has the effective action similar to 2 % lidocaine . One-hundred and thirty-two patients were r and omly assigned to one of the six groups according to concentration and dosage of lidocaine administered at the time of the initiation of propofol infusion . Groups I and II received 1 ml and 2 ml of 1 % lidocaine , respectively ; Groups III and IV were given 1 ml and 2 ml of 0.5 % lidocaine , respectively ; Group V received 2 ml of 2 % lidocaine ; Group VI was administered 1 ml of normal saline as a control . There were no significant differences in patients ' profiles and alterations of hemodynamics during anesthetic induction among the six groups . Number of patients complaining of a pain during induction was more in Group VI with significance ( P < 0.0001 ) and number of patients complaining of uncomfortableness was also more with significance ( P < 0.0001 ) . Incidence of propofol-induced pain and degree of satisfaction with anesthetic induction were similar among the groups receiving lidocaine . Even 0.5 % lidocaine may have the same effective action as 2 % lidocaine for preventing the pain on injection of propofol Pain on injection of propofol was assessed in a controlled , r and omised study of 273 patients . They received either lignocaine 10 mg , procaine 10 mg or isotonic saline 0.5 ml , 15 seconds before the injection of propofol into a vein on the back of the h and . The incidence of pain on injection in the'control group ( 51 % ) was comparable with other studies . Lignocaine and procaine both significantly reduced the pain ( 35 % and 34 % respectively , p < 0.05 ) but there was no statistical difference between these two groups BACKGROUND : Propofol is well-known for its pain on injection . Premixture with lidocaine or pretreatment with remifentanil reduces injection pain . A multimodal approach might offer additional mitigation of propofol injection pain . METHODS : In a r and omized , prospect i ve , double-blind study of 156 patients , we compared the incidence and severity of propofol pain among three groups . Patients in the lidocaine group ( n = 54 ) received 2 % lidocaine premixed with propofol ( 40 mg lidocaine in 180 mg propofol ) . Patients in the remifentanil group ( n = 50 ) , received pretreatment with remifentanil 2 & mgr;g · kg−1 IV over 30 s. Patients in the combination group ( n = 52 ) received both lidocaine and remifentanil . RESULTS : A significant decrease in the overall incidence of propofol pain at induction was achieved in the combination group ( 9.6 % ) compared with that in the remifentanil group ( 36 % ) and the lidocaine group ( 35 % ) ( P = 0.003 ) . The incidence of severe and moderate pain was also significantly different in the combination group ( 0 % ) , compared with that in the remifentanil ( 18 % ) and lidocaine groups ( 12.9 % ) ( P < 0.02 ) . Similar , statistically significant differences among the three groups were achieved concerning recalled pain in the postanesthesia care unit . CONCLUSIONS : The combination of two different analgesic modalities , remifentanil and lidocaine completely abolishes moderate and severe pain associated with propofol injection , and significantly reduces the incidence of mild pain when compared with each drug used alone Propofol formulated in medium- and long-chain tri-glycerides ( MCT/LCT ) is thought to cause less pain on injection . In this study we sought to determine if adding lidocaine to propofol-MCT/LCT is more effect-ive in decreasing pain compared with propofol-MCT/LCT alone or conventional propofol-lidocaine mixtures . Seventy-five patients were r and omized into three groups . Group A received conventional propofol-lidocaine mixtures with 20 mg lidocaine , group B received propofol-MCT/LCT with saline , and group C received propofol-MCT/LCT with 20 mg lidocaine . The incidence of pain was 24 % in groups A and B and 4 % in group C. The number needed to treat to prevent pain was 5 . We conclude that propofol-MCT/LCT-lidocaine mixtures significantly reduce pain Background and objective The aim of this study was to compare the efficacy of pretreatment with paracetamol 0.5 mg kg−1 , 1 mg kg−1 , 2 mg kg−1 and lidocaine 0.5 mg kg−1 for prevention of propofol induced pain . Methods In this double-blind , placebo-controlled study , 250 adult patients ASA I or II , scheduled to undergo elective surgery , were r and omly assigned into five groups of 50 each . Group P0.5 , group P1 and group P2 received 0.5 , 1 and 2 mg kg−1 paracetamol respectively ; group L received 0.5 mg kg−1 lidocaine ; and the control group , group C , received isotonic saline pretreatment in the dorsum of the h and , followed by propofol 1 min later . A blinded research er assessed the patient 's pain level via a four-point scale . Results There were no significant differences in patient characteristics among the groups . The incidence of propofol injection pain in all treatment groups was significantly lower than in the control group ( P < 0.001 ) . When the paracetamol 0.5 mg kg−1 group was compared with both the paracetamol 1 mg kg−1 group ( P < 0.01 ) and the paracetamol 2 mg kg−1 group ( P < 0.001 ) , significant differences were observed . In the lidocaine 0.5 mg kg−1 group propofol injection pain was significantly reduced compared with the paracetamol 0.5 mg kg−1 group ( P < 0.01 ) . However , in the paracetamol 2 mg kg−1 group pain was more significantly reduced than in the lidocaine 0.5 mg kg−1 group ( P < 0.001 ) . In the paracetamol 2 mg kg−1 group the incidence of pain was significantly less than in paracetamol 1 mg kg−1 group ( P < 0.001 ) . Conclusion When given as venous retention pretreatments 1 min before propofol , paracetamol 1 mg kg−1 and lidocaine 0.5 mg kg−1 were equally effective in attenuating pain during intravenous ( i.v . ) injection of propofol whereas pretreatment with paracetamol 2 mg kg−1 was shown to be the most effective treatment BACKGROUND The incidence of pain on injection of propofol remains unacceptably high in children , despite various strategies to reduce it . A new drug formulation of propofol has , in adult studies , been reported to cause less injection pain compared with other propofol solutions . The aim of the present prospect i ve r and omized double-blind clinical trial was to compare the incidence of pain-free injection following the use of this new formulation with that following the use of propofol with added lidocaine in children undergoing day case surgery . METHODS Eighty-three children ( age range 2 - 18 yr ) were r and omized to receive 3 mg kg(-1 ) of either Propofol-Lipuro ( propofol dissolved in a mixture of medium- and long-chain triglycerides [ MCT-LCT ] ; group pL , n=42 ) or Diprivan ( propofol dissolved in long-chain triglycerides [ LCT ] ) with added lidocaine ( 0.3 mg kg(-1 ) ) ( group pD , n=41 ) . A specially trained nurse anaesthetist assessed the occurrence of injection pain using a four- grade d pain scale . RESULTS Significantly fewer patients had an entirely pain-free propofol injection in group pL ( 33.3 % ) than in group pD ( 61.0 % ) ( P=0.016 ) . CONCLUSIONS A new MCT-LCT propofol formulation as a plain solution was associated with a higher incidence of injection pain than LCT propofol with added lidocaine when used for induction of anaesthesia in children STUDY OBJECTIVE To define the optimal dose of lidocaine to be added to propofol to reduce the incidence of pain during its injection . DESIGN Double-blind , r and omized , placebo-controlled study . SETTING Medical center operating rooms . PATIENTS 135 ASA I and II female patients undergoing minor outpatient surgery . INTERVENTIONS Patients were r and omly allocated to one of five groups : Group A ( control ) , no lidocaine : Group B , lidocaine 10 mg : Group C , lidocaine 20 mg ; Group D , lidocaine 30 mg ; Group F , lidocaine 40 mg . For each patient , pain during injection of the propofol solution was grade d as none , mild , moderate , or severe . MEASUREMENTS AND MAIN RESULTS The incidence of pain in the control group was 85 % . All treatment groups receiving lidocaine had a significantly lower incidence of pain compared with the control group ( P < 0.001 ) . The lidocaine 30 mg and 40 mg groups both had a 7 % incidence of pain , which was significantly less than a 33 % incidence in the lidocaine 10 mg group ( P < 0.05 ) . CONCLUSIONS Within this dose range and in this patient population , 30 mg of lidocaine is optimal for reducing the pain during injection of propofol In a single‐blind study of 100 children aged 1 to 10 years , the minimum effective dose of lignocaine required to prevent injection pain due to propofol was 0.2mg.kg−1 when veins on the dorsum of the h and were used . This is more than twice the adult value . We concluded that injection pain should not limit the use of propofol in children if an adequate amount of lignocaine is mixed immediately prior to injection Pain is a well known complication of propofol injection . Premixing with lignocaine 0.1 mg.kg−1 and injection into a large forearm vein has been recommended . The amount of lignocaine to be added is often empirical when the vein on the dorsum of the h and is used . In this study we attempt to determine the optimal amount of lignocaine necessary to reduce pain when propofol is injected into a h and vein . Our study shows that a propofol emulsion containing 0.05 % lignocaine is effective in reducing the incidence of propofol injection pain . The addition of lignocaine also reduces the incidence of excitatory effects . Increasing the dosage of lignocaine above 0.05 % does not improve the results |
1,615 | 25,812,932 | The high incidence of complications such as moderate and severe bleeding or infection in the control groups has to be attributed to interventions with other LVAD .
Available evidence suggests that IABP may have a beneficial effect on some haemodynamic parameters .
However , this did not result in survival benefits so there is no convincing r and omised data to support the use of IABP in infa rct -related cardiogenic shock | BACKGROUND Intra-aortic balloon pump counterpulsation ( IABP ) is currently the most commonly used mechanical assist device for patients with cardiogenic shock due to acute myocardial infa rct ion .
Although there has been only limited evidence from r and omised controlled trials , the previous guidelines of the American Heart Association/American College of Cardiology ( AHA/ACC ) and the European Society of Cardiology ( ESC ) strongly recommended the use of the IABP in patients with infa rct ion-related cardiogenic shock on the basis of pathophysiological considerations , non-r and omised trials and registry data .
The recent guidelines down grade d the recommendation based on a meta- analysis which could only include non-r and omised trials showing conflicting results .
Up to now , there have been no guideline recommendations and no actual meta- analysis including the results of the large r and omised multicentre IABP-SHOCK II Trial which showed no survival benefit with IABP support .
OBJECTIVES To evaluate , in terms of efficacy and safety , the effect of IABP versus non-IABP or other assist devices guideline compliant st and ard therapy on mortality and morbidity in patients with acute myocardial infa rct ion complicated by cardiogenic shock . | Background : Sustained hypotension , cardiogenic shock , and heart failure all imply a poor prognosis in acute myocardial infa rct ion ( MI ) . We assessed the benefit of adding 48 hours of intra-aortic balloon counterpulsation ( IABP ) to st and ard treatment for MI , in an international trial among hospitals without primary angioplasty capabilities . Methods : We r and omized 57 patients with MI complicated by sustained hypotension , possible cardiogenic shock , or possible heart failure to receive either fibrinolytic therapy and IABP or fibrinolysis alone . The primary end point was all-cause mortality at 6 months . Results : In all , IABP was inserted in 27 of 30 assigned patients a median 30 minutes after fibrinolysis began and continued for a median 34 hours . Of the 27 patients assigned to fibrinolysis alone , 9 deteriorated such that IABP was required . The IABP group was at slightly higher risk at baseline , but the incidence of the primary end point did not differ significantly between groups ( 34 % for combined treatment versus 43 % for fibrinolysis alone ; adjusted P = 0.23 ) . Patients with Killip class III or IV showed a trend toward greater benefit from IABP ( 6-month mortality 39 % for combined therapy versus 80 % for fibrinolysis alone ; P = 0.05 ) . Conclusions : While early IABP use was not associated with a definitive survival benefit when added to fibrinolysis for patients with MI and hemodynamic compromise in this small trial , its use suggested a possible benefit for patients with the most severe heart failure or hypotension . Abbreviated Abstract . We assessed the benefit of adding 48 hours of intra-aortic balloon counterpulsation to fibrinolytic therapy among 57 patients with acute myocardial infa rct ion complicated by sustained hypotension , possible cardiogenic shock , or possible heart failure . The primary end point , mortality at 6 months , did not differ between groups ( 34 % for combined treatment versus 43 % for fibrinolysis alone [ n = 27 ] ; adjusted P = 0.23 ) , although patients with Killip class III or IV did show a trend toward greater benefit from IABP ( 39 % for combined therapy versus 80 % for fibrinolysis ; P = 0.05 ) Objective : Patients undergoing percutaneous coronary intervention ( PCI ) for acute myocardial infa rct ion with cardiogenic shock ( CS ) are often treated with intra-aortic balloon pump counterpulsation ( IABP ) , even though the evidence to support this is limited . We determined whether IABP as an addition to PCI-centered therapy ameliorates multiorgan dysfunction syndrome ( MODS ) in patients with acute myocardial infa rct ion complicated by CS . Design : A prospect i ve , r and omized , controlled , open-label clinical trial recruiting patients between March 2003 and June 2004 ( Clinical Trials.gov ID NCT00469248 ) . Setting : Tertiary care university hospital . Patients and Interventions : Forty-five consecutive patients with AMI and CS undergoing PCI were r and omized to treatment with or without IABP . Measurements and Main Results : Acute Physiology and Chronic Health Evaluation ( APACHE ) II scores ( primary outcome measure ) , hemodynamic values , inflammatory markers , and plasma brain natriuretic peptide ( BNP ) levels ( secondary outcomes ) were collected over 4 days from r and omization . The prospect i ve hypothesis was that adding IABP therapy to “ st and ard care ” would improve CS-triggered MODS . The addition of IABP to st and ard therapy did not result in a significant improvement in MODS ( measured by serial APACHE II scoring over 4 days ) . IABP use had no significant effect on cardiac index or systemic inflammatory activation , although BNP levels were significantly lower in IABP-treated patients . Initial and serial APACHE II scoring correlated with mortality better than cardiac index , systemic inflammatory state , and BNP levels in this group of patients . Nonsurvivors had significantly higher initial APACHE II scores ( 29.9 ± 2.88 ) than survivors ( 18.1 ± 1.66 , p < .05 ) . Nevertheless , discrepancies among patients within the groups can not be ruled out and might interfere with our results . Conclusions : In this r and omized trial addressing addition of IABP in CS patients , mechanical support was associated only with modest effects on reduction of APACHE II score as a marker of severity of disease , improvement of cardiac index , reduction of inflammatory state , or reduction of BNP biomarker status compared with medical therapy alone . However , the limitations of our present trial preclude any definitive conclusion , but request for a larger prospect i ve , r and omized , multicentered trial with mortality as primary end point BACKGROUND AND AIM Despite major advances in the treatment of heart failure , cardiogenic shock ( CGS ) remains associated with substantial mortality . Recent data suggest that the T and emHeart percutaneous ventricular assist device ( pVAD ) may be useful in the management of CGS . The aim of this prospect i ve r and omized study was to test the hypothesis that the T and emHeart ( pVAD ) provides superior hemodynamic support compared with intraaortic balloon pumping ( IABP ) . METHODS Forty-two patients from 12 centers presenting within 24 hours of developing CGS were included in the study and treated in an initial roll-in phase ( n = 9 ) or r and omized to treatment with IABP ( n = 14 ) or T and emHeart pVAD ( n = 19 ) . Thirty patients ( 71 % ) had persistent CGS despite having an IABP in place at the time of study enrollment . RESULTS Cardiogenic shock was due to myocardial infa rct ion in 70 % of the patients and decompensated heart failure in most of the remaining patients . The mean duration of support was 2.5 days . Compared with IABP , the T and emHeart pVAD achieved significantly greater increases in cardiac index and mean arterial blood pressure and significantly greater decreases in pulmonary capillary wedge pressure . Overall 30-day survival and severe adverse events were not significantly different between the 2 groups . CONCLUSION In patients presenting within 24 hours of the development of CGS , T and emHeart significantly improves hemodynamic parameters , even in patients failing IABP . Larger-scale studies are required to assess the influence of improved hemodynamics on survival BACKGROUND In current international guidelines the recommendation for intra-aortic balloon pump ( IABP ) use has been down grade d in cardiogenic shock complicating acute myocardial infa rct ion on the basis of registry data . In the largest r and omised trial ( IABP-SHOCK II ) , IABP support did not reduce 30 day mortality compared with control . However , previous trials in cardiogenic shock showed a mortality benefit only at extended follow-up . The present analysis therefore reports 6 and 12 month results . METHODS The IABP-SHOCK II trial was a r and omised , open-label , multicentre trial . Patients with cardiogenic shock complicating acute myocardial infa rct ion who were undergoing early revascularisation and optimum medical therapy were r and omly assigned ( 1:1 ) to IABP versus control via a central web-based system . The primary efficacy endpoint was 30 day all-cause mortality , but 6 and 12 month follow-up was done in addition to quality -of-life assessment for all survivors with the Euroqol-5D question naire . A masked central committee adjudicated clinical outcomes . Patients and investigators were not masked to treatment allocation . Analysis was by intention to treat . This trial is registered at Clinical Trials.gov , NCT00491036 . FINDINGS Between June 16 , 2009 , and March 3 , 2012 , 600 patients were assigned to IABP ( n=301 ) or control ( n=299 ) . Of 595 patients completing 12 month follow-up , 155 ( 52 % ) of 299 patients in the IABP group and 152 ( 51 % ) of 296 patients in the control group had died ( relative risk [ RR ] 1·01 , 95 % CI 0·86 - 1·18 , p=0·91 ) . There were no significant differences in reinfa rct ion ( RR 2·60 , 95 % CI 0·95 - 7·10 , p=0·05 ) , recurrent revascularisation ( 0·91 , 0·58 - 1·41 , p=0·77 ) , or stroke ( 1·50 , 0·25 - 8·84 , p=1·00 ) . For survivors , quality -of-life measures including mobility , self-care , usual activities , pain or discomfort , and anxiety or depression did not differ significantly between study groups . INTERPRETATION In patients undergoing early revascularisation for myocardial infa rct ion complicated by cardiogenic shock , IABP did not reduce 12 month all-cause mortality . FUNDING German Research Foundation ; German Heart Research Foundation ; German Cardiac Society ; Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte ; University of Leipzig -- Heart Centre ; Maquet Cardiopulmonary ; Teleflex Medical OBJECTIVES Our goal was to describe the functional status of cardiogenic shock survivors , identify the correlates of cardiogenic shock , and compare global quality of life and functional status of patients r and omly assigned to treatment with emergency revascularization ( ERV ) versus initial medical stabilization ( IMS ) . BACKGROUND Historically , the hospital survival rate of patients with cardiogenic shock complicating acute myocardial infa rct ion ( MI ) has been very low . Shock survivors are salvaged from a critically ill state , and their later functional status is not well documented . The SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK ( SHOCK ) trial showed significantly improved one-year survival after ERV compared with IMS . METHODS The SHOCK trial survivors completed interviews at 2 weeks after discharge and at 6 and 12 months after MI . Functional status assessment included the Multidimensional Index of Life Quality and New York Heart Association ( NYHA ) congestive heart failure functional class . RESULTS Eighty-seven percent of one-year survivors of the SHOCK trial were in NYHA functional class I or II . Between two weeks after discharge and one year after MI , improvement was similar in the two treatment groups ( 18 % overall ) , but fewer patients remained stable ( 44 % vs. 71 % ) , and more patients worsened or died ( 34 % vs. 15 % ) in the IMS group compared with those assigned to ERV . Assignment to ERV was the only independent predictor of outcome at one year . CONCLUSIONS Although one-year mortality after ERV is still high ( 54 % ) , most survivors have good functional status . The ERV patients have a lower rate of deterioration than IMS patients . The level of recovery for shock patients undergoing ERV is similar to that of historical controls not in cardiogenic shock undergoing elective revascularization Background Aortic counterpulsation has been observed to reduce the rate of reocclusion of the infa rct -related artery after patency has been restored during acute myocardial infa rct ion in observational studies . To evaluate the benefit-to-risk ratio of aortic counterpulsation during the early phase of myocardial infa rct ion , a multicenter r and omized clinical trial was performed . Methods and Results Patients who had patency restored during acute cardiac catheterization within the first 24 hours of onset of myocardial infa rct ion were r and omly assigned to aortic counterpulsation for 48 hours versus st and ard care . Intravenous heparin was used similarly in both groups and was continued for a median ( 25th , 75th percentile ) of 5 ( 2,7 ) days . A total of 182 patients were enrolled ; 96 were assigned to aortic counterpulsation and 86 to st and ard care . Repeat cardiac catheterization was performed at a median of 5 ( 4,6 ) days after r and omization in 89 % of patients assigned to aortic counterpulsation and in 90 % of control patients . Patients r and omized to aortic counterpulsation had similar rates of severe bleeding complications ( 2 % versus 1 % ) , number of units of blood transfused ( mean , 1.3±2.6 versus 0.9±1.8 units ) , and vascular repair or thrombectomy ( 5 % versus 2 % ) compared with patients treated in a conventional manner . Patients r and omized to aortic counterpulsation had significantly less reocclusion of the infa rct -related artery during follow-up compared with control patients ( 8 % versus 21 % , P<.03 ) . In addition , there was a significantly lower event rate in patients assigned to aortic counterpulsation in terms of a composite clinical end point ( death , stroke , reinfa rct ion , need for emergency revascularization with angioplasty or bypass surgery , or recurrent ischemia ) : 13 % versus 24 % , P<.04 . Conclusions This r and omized trial showed that careful use of prophylactic aortic counterpulsation can prevent reocclusion of the infa rct -related artery and improve overall clinical outcome in patients undergoing acute cardiac catheterization during myocardial infa rct ion Background : The benefit of heparin anticoagulation in patients undergoing intra-aortic balloon counterpulsation ( IABP ) is unproven . Methods : We determined the net clinical benefit ( or harm ) of heparin therapy during intra-aortic balloon counterpulsation ( IABP ) in the coronary care unit ( CCU ) by conducting a prospect i ve “ before- and -after ” analysis of consecutive patients . We compared a universal heparin ( UH ) strategy ( all patients given heparin ) to a selective heparin ( SH ) strategy ( heparin only for a clinical indication ) . Results : There were 102 patients in the UH group and 150 patients in the SH group . Among the SH group , 70 patients ( 47 % ) received no heparin . Major IABP-related complications were uncommon in both groups ( 2.9 % versus 4.6 % , P=0.7 ) . Major limb ischemia occurred in one patient in the UH group ( overall incidence : 0.4 % ) . Major non-access-site bleeding was more common in the UH group ( 10.8 % versus 3.3 % , P=0.02 ) . Inclusion in the UH group was independently associated with the endpoints of : major limb ischemia or any major bleeding ( odds ratio ( OR ) 3.32 , P=0.03 ) , any major bleeding ( OR 3.35 , P=0.03 ) , and major limb ischemia , any major bleeding , or death ( OR 2.17 , P=0.03 ) . Conclusions : Among CCU patients undergoing IABP , a selective heparin strategy appears to be superior to a strategy of universal heparin use AIMS Intra-aortic balloon pumping reduces afterload and may be effective in improving reperfusion in high risk infa rct patients treated with primary angioplasty . METHODS High risk infa rct patients referred from other centres for primary PTCA were r and omized to treatment with or without an intra-aortic balloon pump . The primary end-point consisted of the combination of death , non-fatal reinfa rct ion , stroke or an ejection fraction < 30 % at the 6 month follow-up . A weighted unsatisfactory outcome score ( as previously described by Braunwald ) , enzymatic infa rct size and left ventricular ejection fraction were secondary end-points . RESULTS During a 3.5 year period , 238 patients were r and omized , 118 to intra-aortic balloon pump therapy and 120 to no intra-aortic balloon pump therapy . Cross-over ( 25 % in the intra-aortic balloon pump group and 31 % in the no-intra-aortic balloon pump group ) occurred in both treatment arms . The primary end-point was reached in 31 ( 26 % ) patients assigned to an intra-aortic balloon pump and in 31 ( 26 % ) assigned to no intra-aortic balloon pump ( P=0.94 ) . Enzymatic infa rct size ( LDHQ72 ) was calculated in 163 ( 68 % ) patients and was not significantly different between either group ( intra-aortic balloon pump : 1616+/-1148 , no intra-aortic balloon pump : 1608+/-1163 ) . The left ventricular ejection fraction was measured at the 6 month follow-up in 168 patients ( 80 % of patients alive ) . No difference in ejection fraction was found in either group ( intra-aortic balloon pump : 42+/-13 % , no intra-aortic balloon pump : 40+/-14 % , P=0.51 ) . Major complications occurred in 8 % of patients treated with an intra-aortic balloon pump . CONCLUSIONS Systematic use of intra-aortic balloon pumping after primary angioplasty does not lead to myocardial salvage or to a better clinical outcome in high-risk infa rct patients . Use of intra-aortic balloon pumping after primary PTCA for acute myocardial infa rct ion should be reserved for patients with severe haemodynamic compromise Several observational studies have suggested that mortality and major complications after high-risk percutaneous coronary intervention ( PCI ) can be reduced by elective insertion of an intra-aortic balloon pump ( IABP ) . However , to date , this assertion has never been tested in a r and omized trial , and as such , international guidelines do not provide formal recommendations for IABP use in this setting . The BCIS-1 is a r and omized trial that addresses the hypothesis that elective IABP insertion before high-risk PCI will reduce major adverse cardiac and cerebrovascular events ( MACCEs ) at hospital discharge or 28 days after index PCI , whichever occurs sooner . High risk is defined by the presence of severe left ventricular dysfunction as well as a large amount of myocardium at risk . Patients who are in cardiogenic shock , have a class I indication for IABP use , or have an absolute contraindication to IABP use will be excluded . Three hundred eligible patients will be r and omized to receive elective IABP insertion or no planned IABP insertion . The findings of BCIS-1 are expected to define the role of balloon counterpulsation in high-risk PCI . Confirmation of the efficacy of elective IABP use may prompt review of the international guidelines , which are currently very restricted . In contrast , a neutral or adverse outcome with elective counterpulsation in these high-risk patients will allow evidence -based rationalization of the current disparity between guidelines and the frequent real-world use of elective IABP support The aim of this study was to review and describe indications for intraaortic balloon counterpulsation ( IABP ) use and identify the impact these have on outcomes at an Australian cardiothoracic tertiary referral hospital . A secondary aim was comparison of the Australian practice with a large multinational IABP data registry . Patient demographics , IABP indication , IABP complication rate and mortality in 662 patients treated with IABP at The Prince Charles Hospital ( TPCH ) , Brisbane , between January 1994 and December 2004 inclusive were compared with The Benchmark Counterpulsation Outcomes Registry . Data were collected between 1994 and 2000 by retrospective patient record review and prospect ively using the Benchmark data base from 2001 to 2004 . Statistical analysis was undertaken usingSAS ( v8.2 ) software . The mean age of patients managed with IABP at TPCH ( 71.6 % male ) was 63.4 years ( SD 12.4 ) . In-hospital mortality rate was 22 % and the complication rate was 10.3 % . TPCH indications for IABP were : weaning from cardiopulmonary bypass ( 34.2 % ) ; cardiogenic shock ( 24.4 % ) ; preoperative support ( 13 % ) ; catheter laboratory support ( 10.6 % ) ; refractory ventricular failure ( 7.3 % ) ; ischaemia related to intractable ventricular arrhythmias ( 4.5 % ) ; unstable refractory angina ( 4 % ) ; mechanical complications due to acute myocardial infa rct ion ( 1.2 % ) and other ( 0.4 % ) ( 0.4 % not reported ) . In comparison to Benchmark , IABP at TPCH demonstrated a prejudice toward intraoperative use ( 34.2 % versus 16.6 % ; P= < 0.0001 ) and an aversion to catheter laboratory support ( 10.6 % versus 19 % ; P= < 0.0001 ) . TPCH and Benchmark IABP outcomes demonstrated comparable mortality ( 22 % versus 20.8 % ; P = ns ) but increased TPCH complications ( 10.3 % vs. 6.2 % ; P= < 0.0001 ) owing to a 2 % difference in observed insertion site bleeding BACKGROUND The combined use of anticoagulants , antiplatelet agents , and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes . We therefore assessed whether fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding . METHODS We r and omly assigned 20,078 patients with acute coronary syndromes to receive either fondaparinux ( 2.5 mg daily ) or enoxaparin ( 1 mg per kilogram of body weight twice daily ) for a mean of six days and evaluated death , myocardial infa rct ion , or refractory ischemia at nine days ( the primary outcome ) ; major bleeding ; and their combination . Patients were followed for up to six months . RESULTS The number of patients with primary - outcome events was similar in the two groups ( 579 with fondaparinux [ 5.8 percent ] vs. 573 with enoxaparin [ 5.7 percent ] ; hazard ratio in the fondaparinux group , 1.01 ; 95 percent confidence interval , 0.90 to 1.13 ) , satisfying the noninferiority criteria . The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the fondaparinux group at 30 days ( 805 vs. 864 , P=0.13 ) and at the end of the study ( 1222 vs. 1308 , P=0.06 ) . The rate of major bleeding at nine days was markedly lower with fondaparinux than with enoxaparin ( 217 events [ 2.2 percent ] vs. 412 events [ 4.1 percent ] ; hazard ratio , 0.52 ; P<0.001 ) . The composite of the primary outcome and major bleeding at nine days favored fondaparinux ( 737 events [ 7.3 percent ] vs. 905 events [ 9.0 percent ] ; hazard ratio , 0.81 ; P<0.001 ) . Fondaparinux was associated with a significantly reduced number of deaths at 30 days ( 295 vs. 352 , P=0.02 ) and at 180 days ( 574 vs. 638 , P=0.05 ) . CONCLUSIONS Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days , but it substantially reduces major bleeding and improves long term mortality and morbidity . ( Clinical Trials.gov number , NCT00139815 . ) OBJECTIVES We sought to examine contemporary utilization patterns and clinical outcomes in patients with acute myocardial infa rct ion ( AMI ) requiring intra-aortic balloon pump ( IABP ) counterpulsation . BACKGROUND Despite increasing experience with and broadened indications for intra-aortic counterpulsation , the current indications , associated complications , and clinical outcomes of IABP use in AMI are unknown . METHODS Between June 1996 and August 2001 , data were prospect ively collected from 22,663 consecutive patients treated with aortic counterpulsation at 250 medical centers worldwide ; 5,495 of these patients had AMI . RESULTS Placement of an IABP in AMI patients was most frequently indicated for cardiogenic shock ( 27.3 % ) , hemodynamic support during catheterization and /or angioplasty ( 27.2 % ) or prior to high-risk surgery ( 11.2 % ) , mechanical complications of AMI ( 11.7 % ) , and refractory post-myocardial infa rct ion unstable angina ( 10.0 % ) . Balloon insertions were successful in 97.7 % of patients . Diagnostic catheterization was performed in 96 % of patients , and 83 % underwent coronary revascularization before hospital discharge . The in-hospital mortality rate was 20.0 % ( 38.7 % in patients with shock ) and varied markedly by indication and use of revascularization procedures . Major IABP complications occurred in only 2.7 % of patients , despite median use for three days , and early IABP discontinuation was required in only 2.1 % of patients . CONCLUSIONS With contemporary advances in device technology , insertion technique , and operator experience , IABP counterpulsation may be successfully employed for a wide variety of conditions in the AMI setting , providing significant hemodynamic support with rare major complications in a high-risk patient population OBJECTIVE The intra-aortic balloon pump ( IABP ) is an established additional support to pharmacological treatment of the failing heart after myocardial infa rct ion , unstable angina and cardiac surgery . The effect of preoperative IABP in high risk patients was evaluated . METHODS Between June 1994 and March 1996 all high risk patients for CABG ( two or more of these criteria : Left ventricular ejection fraction ( LVEF ) < or = 40 % , left main stem stenosis > or = 70 % , REDO-CABG , unstable angina ) were r and omized into either of 3 groups : ( 1 ) IABP 1 day prior to surgery , ( 2 ) IABP 1 - 2 h prior to CPB and ( 3 ) no preoperative IABP , controls . EXCLUSION CRITERIA cardiogenic shock preoperatively . Fifty-two patients have entered the study -group 1 ( 13 patients ) , group 2 ( 19 patients ) and group 3 ( 20 patients ) . Preoperative patient characteristics and operative data revealed no group differences . There were 56 % REDO 's , unstable angina 59 % , LVEF < or = 40 % , 87 % ( 34.0 + /- 11.6 % ) and left main stem stenosis in 35 % . RESULTS The CPB-time was shorter in groups 1 and 2 88.7 + /- 20.3 min than in group 3 105.5 + /- 26.8 min , P < 0.001 , while ischemia time did not differ . Hospital mortality was higher in group 3 , 25 % vs. 6 % ( groups 1 and 2 ) . Postoperative low cardiac output was seen in 12 patients ( 60 % ) in group 3 vs. 6 patients ( 19 % ) in groups 1 and 2 , P < 0.05 . Cardiac index increased significantly prior to CPB in groups 1 and 2 . After CPB cardiac index was significantly higher in groups 1 and 2 compared to Group 3 and continued to increase . The IABP was removed after 3.1 + /- 1.0 days in group 3 vs. 1.3 + /- 0.6 days in groups 1 and 2 , P < 0.001 . In group 3 , 11 patients required IABP postoperatively compared to only 4 patients in groups 1 and 2 . ICU stay was shorter in groups 1 and 2 - -2.3 + /- 0.9 days vs. 3.5 + /- 1.1 days for group 3 , P = 0.004 . All patients received dopamin postoperatively , however in a lower dose in groups 1 and 2 , 4.5 vs. 13.5 microg/kg/min . Dobutamine was added in 23 % of the patients ( group 1 ) , 32 % ( group 2 ) and 95 % ( group 3 ) . Adrenalin/amrinonum was required in 40 % of the patients in group 3 , 5 % in group 2 and none in group 1 . Group 1 patients had a better improvement of cardiac performance than group 2 , while other parameters did not differ . Three months follow up of hospital survivors showed no group differences . CONCLUSIONS The use of preoperative IABP in high risk patients lowers hospital mortality and shortens the stay in ICU , due to improved cardiac performance , compared to a controls . The procedure was cost-beneficial . One day preoperative IABP treatment improves cardiac performance more than 1 - 2 h preoperative IABP treatment , but does not significantly affect the outcome in terms of hospital mortality or postoperative morbidity UNLABELLED The intra-aortic balloon pump ( IABP ) is the most commonly used temporary cardiac assist device . The precise role and the mechanism of any benefit in high-risk patients undergoing percutaneous coronary intervention ( PCI ) have not been fully determined . We hypothesized that the use of an IABP following PCI in high-risk non-shocked patients would immediately increase coronary blood flow , tissue perfusion and hence preserve left ventricular function . METHODS Predefined high-risk , but non-shocked , patients were r and omized to either an IABP or no IABP following PCI . Angiography was performed pre-PCI , immediately post-PCI and 10 minutes after the completion of the procedure . TIMI flow grade ( TFG ) , TIMI frame count ( TFC ) and myocardial blush grade ( MBG ) were measured . Echocardiographic wall motion index ( WMI ) was measured on days 1 and 30 following PCI . RESULTS Of 33 patients , 17 received IABP and 16 did not . At final angiography , the TFG was 2.8 + /- 0.7 and 2.9 + /- 0.3 ( p = 0.6 ) , the TFC was 19.9 + /- 23 and 16.9 + /- 16.9 ( p = 0.7 ) , and the MBG was 2.5 + /- 0.9 and 2.5 + /- 0.7 ( p = 0.9 ) in the IABP and the no-IABP arms . The WMI on day 1 was 1.7 + /- 0.4 and 1.7 + /- 0.4 ( p = 0.7 ) , and on day 30 , it was 1.5 + /- 0.4 and 1.5 + /- 0.4 ( p = 0.9 ) . There was no difference in the total sum of ST-segment elevation prior to PCI ( 12.6 + /- 7.7 vs. 13.5 + /- 7.9 ; p = 0.8 ) , nor in the summed ST change in subsequent electrocardiograms ( ECGs ) to 48 hours in both of the groups . CONCLUSION Whether an IABP is of any benefit in non-shocked , but high-risk , patients undergoing PCI remains to be established , but any potential benefit does not appear to be associated with early improvement in coronary flow . Whether the insertion of an IABP improves coronary flow beyond 10 minutes is not known . However , the IABP did not significantly affect subsequent left ventricular wall motion index or ECG ST-segment resolution in this study BACKGROUND The leading cause of death in patients hospitalized for acute myocardial infa rct ion is cardiogenic shock . We conducted a r and omized trial to evaluate early revascularization in patients with cardiogenic shock . METHODS Patients with shock due to left ventricular failure complicating myocardial infa rct ion were r and omly assigned to emergency revascularization ( 152 patients ) or initial medical stabilization ( 150 patients ) . Revascularization was accomplished by either coronary-artery bypass grafting or angioplasty . Intraaortic balloon counterpulsation was performed in 86 percent of the patients in both groups . The primary end point was mortality from all causes at 30 days . Six-month survival was a secondary end point . RESULTS The mean age of the patients was 66+/-10 years , 32 percent were women and 55 percent were transferred from other hospitals . The median time to the onset of shock was 5.6 hours after infa rct ion , and most infa rcts were anterior in location . Ninety-seven percent of the patients assigned to revascularization underwent early coronary angiography , and 87 percent underwent revascularization ; only 2.7 percent of the patients assigned to medical therapy crossed over to early revascularization without clinical indication . Overall mortality at 30 days did not differ significantly between the revascularization and medical-therapy groups ( 46.7 percent and 56.0 percent , respectively ; difference , -9.3 percent ; 95 percent confidence interval for the difference , -20.5 to 1.9 percent ; P=0.11 ) . Six-month mortality was lower in the revascularization group than in the medical-therapy group ( 50.3 percent vs. 63.1 percent , P=0.027 ) . CONCLUSIONS In patients with cardiogenic shock , emergency revascularization did not significantly reduce overall mortality at 30 days . However , after six months there was a significant survival benefit . Early revascularization should be strongly considered for patients with acute myocardial infa rct ion complicated by cardiogenic shock BACKGROUND The role of inflammation in patients with coronary artery disease is emerging . We sought to assess the profile and outcomes of patients with a clinical syndrome of severe systemic inflammation that led to a diagnosis of suspected sepsis in the setting of acute myocardial infa rct ion complicated by cardiogenic shock ( CS ) . METHODS Patients enrolled in the r and omized SHOCK ( SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK ) trial ( n = 302 ) were divided into those with clinical signs of severe systemic inflammation ( eg , fever [ 94 % ] or leukocytosis [ 72 % ] ) that led to a diagnosis of suspected sepsis ( n = 54 [ 18 % ] ) and those without suspected sepsis ( controls ; n = 243 [ 80 % ] ) . The patients with suspected sepsis were then further subdivided into those who were considered to be potentially infectious ( positive culture result [ " culture-positive " ] ; n = 40 ) and those who were not ( negative culture result [ " culture-negative " ] ; n = 14 ) . RESULTS Severe systemic inflammation was diagnosed 4 and 2 days after the onset of CS in culture-positive and culture-negative patients , respectively . Patients who developed systemic inflammation tended to be younger ( P = .05 ) and to have lower systemic vascular resistance ( SVR ) near the onset of CS ( P = .006 ) . Many culture-positive patients ( 40 % ) had undergone coronary artery bypass graft surgery . However , the lower the initial SVR , the higher the risk of developing culture-positive systemic inflammation ( P = .01 ) , even after controlling for age and coronary artery bypass graft surgery . A time-dependent model , adjusted for age , showed that culture-positive patients were at significantly higher risk for death than were controls ( hazard ratio , 2.22 ; 95 % confidence interval , 1.32 - 3.76 ; P = .008 ) . CONCLUSIONS Almost one fifth of patients with acute myocardial infa rct ion complicated by CS showed clinical signs of severe systemic inflammation , and those who were culture-positive for sepsis had twice the risk of death . The observation of lower SVR at the onset of shock in patients who subsequently had culture-positive systemic inflammation suggests that inappropriate vasodilation may play an important role in the pathogenesis and persistence of shock and in the risk of infection OBJECTIVES We sought to investigate the potential benefit of thrombolytic therapy ( TT ) and intra-aortic balloon pump counterpulsation ( IABP ) on in-hospital mortality rates of patients enrolled in a prospect i ve , multi-center Registry of acute myocardial infa rct ion ( MI ) complicated by cardiogenic shock ( CS ) . BACKGROUND Retrospective studies suggest that patients suffering from CS due to MI have lower in-hospital mortality rates when IABP support is added to TT . This hypothesis has not heretofore been examined prospect ively in a study devoted to CS . METHODS Of 1,190 patients enrolled at 36 participating centers , 884 patients had CS due to predominant left ventricular ( LV ) failure . Excluding 26 patients with IABP placed prior to shock onset and 2 patients with incomplete data , 856 patients were evaluated regarding TT and IABP utilization . Treatments , selected by local physicians , fell into four categories : no TT , no IABP ( 33 % ; n = 285 ) ; IABP only ( 33 % ; n = 279 ) ; TT only ( 15 % ; n = 132 ) ; and TT and IABP ( 19 % ; n = 160 ) . RESULTS Patients in CS treated with TT had a lower in-hospital mortality than those who did not receive TT ( 54 % vs. 64 % , p = 0.005 ) , and those selected for IABP had a lower in-hospital mortality than those who did not receive IABP ( 50 % vs. 72 % , p < 0.0001 ) . Furthermore , there was a significant difference in in-hospital mortality among the four treatment groups : TT + IABP ( 47 % ) , IABP only ( 52 % ) , TT only ( 63 % ) , no TT , no IABP ( 77 % ) ( p < 0.0001 ) . Patients receiving early IABP ( < or = 6 h after thrombolytic therapy , n = 72 ) had in-hospital mortality similar to those with late IABP ( 53 % vs. 41 % , n = 64 , respectively , p = 0.172 ) . Revascularization rates differed among the four groups : no TT , no IABP ( 18 % ) ; IABP only ( 70 % ) ; TT only ( 20 % ) ; TT and IABP ( 68 % , p < 0.0001 ) ; this influenced in-hospital mortality significantly ( 39 % with revascularization vs. 78 % without revascularization , p < 0.0001 ) . CONCLUSIONS Treatment of patients in cardiogenic shock due to predominant LV failure with TT , IABP and revascularization by PTCA/CABG was associated with lower in-hospital mortality rates than st and ard medical therapy in this Registry . For hospitals without revascularization capability , a strategy of early TT and IABP followed by immediate transfer for PTCA or CABG may be appropriate . However , selection bias is evident and further investigation is required BACKGROUND In current international guidelines , intraaortic balloon counterpulsation is considered to be a class I treatment for cardiogenic shock complicating acute myocardial infa rct ion . However , evidence is based mainly on registry data , and there is a paucity of r and omized clinical trials . METHODS In this r and omized , prospect i ve , open-label , multicenter trial , we r and omly assigned 600 patients with cardiogenic shock complicating acute myocardial infa rct ion to intraaortic balloon counterpulsation ( IABP group , 301 patients ) or no intraaortic balloon counterpulsation ( control group , 299 patients ) . All patients were expected to undergo early revascularization ( by means of percutaneous coronary intervention or bypass surgery ) and to receive the best available medical therapy . The primary efficacy end point was 30-day all-cause mortality . Safety assessment s included major bleeding , peripheral ischemic complications , sepsis , and stroke . RESULTS A total of 300 patients in the IABP group and 298 in the control group were included in the analysis of the primary end point . At 30 days , 119 patients in the IABP group ( 39.7 % ) and 123 patients in the control group ( 41.3 % ) had died ( relative risk with IABP , 0.96 ; 95 % confidence interval , 0.79 to 1.17 ; P=0.69 ) . There were no significant differences in secondary end points or in process-of-care measures , including the time to hemodynamic stabilization , the length of stay in the intensive care unit , serum lactate levels , the dose and duration of catecholamine therapy , and renal function . The IABP group and the control group did not differ significantly with respect to the rates of major bleeding ( 3.3 % and 4.4 % , respectively ; P=0.51 ) , peripheral ischemic complications ( 4.3 % and 3.4 % , P=0.53 ) , sepsis ( 15.7 % and 20.5 % , P=0.15 ) , and stroke ( 0.7 % and 1.7 % , P=0.28 ) . CONCLUSIONS The use of intraaortic balloon counterpulsation did not significantly reduce 30-day mortality in patients with cardiogenic shock complicating acute myocardial infa rct ion for whom an early revascularization strategy was planned . ( Funded by the German Research Foundation and others ; IABP-SHOCK II Clinical Trials.gov number , NCT00491036 . ) Background —Recovery of myocardial function after revascularization of acutely occluded coronary arteries may require several days . During this critical time , patients in cardiogenic shock may have low output . A newly developed percutaneous left ventricular assist device ( VAD ) may offer effective treatment for these patients by providing active circulatory support . Methods and Results —Between May 2000 and May 2001 , VADs were implanted in 18 consecutive patients who had cardiogenic shock after myocardial infa rct ion . The device was connected to the patient ’s circulation by insertion of a 21F venous cannula into the left atrium by transseptal puncture ; blood was returned to the iliac artery through an arterial cannula . Mean duration of cardiac assistance was 4±3 days . Mean flow of the VAD was 3.2±0.6 L/min . Before support , cardiac index was 1.7±0.3 L/min per m2 and improved to 2.4±0.6 L/min per m2 ( P < 0.001 ) . Mean blood pressure increased from 63±8 mm Hg to 80±9 mm Hg ( P < 0.001 ) . Pulmonary capillary wedge pressure , central venous pressure , and pulmonary artery pressure were reduced from 21±4 , 13±4 , and 31±8 mm Hg to 14±4 , 9±3 , and 23±6 mm Hg ( all P < 0.001 ) , respectively . Overall 30-day mortality rate was 44 % . Conclusions —A newly developed VAD can be rapidly deployed in the catheterization laboratory setting . This device provides up to 4.0 L/min of assisted cardiac output , which may aid to revert cardiogenic shock . The left ventricle is unloaded by diverting blood from the left atrium to the systemic circulation , making recovery more likely after an ischemic event . The influence of this device on long-term prognosis warrants further investigation AIMS Mortality in cardiogenic shock ( CS ) following acute myocardial infa rct ion ( AMI ) remains unacceptably high despite percutaneous coronary intervention ( PCI ) of the infa rct ed artery and use of intra-aortic balloon pump ( IABP ) counterpulsation . A newly developed percutaneous left ventricular assist device ( VAD ) ( T and em Heart , Cardiac Assist , Pittsburgh , PA , USA ) with active circulatory support might have positive haemodynamic effects and decrease mortality . METHODS AND RESULTS Patients in CS after AMI , with intended PCI of the infa rct ed artery , were r and omized to either IABP ( n=20 ) or percutaneous VAD support ( n=21 ) . The primary outcome measure cardiac power index , as well as other haemodynamic and metabolic variables , could be improved more effectively by VAD support from 0.22 [ interquartile range ( IQR ) 0.19 - 0.30 ] to 0.37 W/m2 ( IQR 0.30 - 0.47 , P<0.001 ) when compared with IABP from 0.22 ( IQR 0.18 - 0.30 ) to 0.28 W/m2 ( IQR 0.24 - 0.36 , P=0.02 ; P=0.004 for intergroup comparison ) . However , complications like severe bleeding ( n=19 vs. n=8 , P=0.002 ) or limb ischaemia ( n=7 vs. n=0 , P=0.009 ) were encountered more frequently after VAD support , whereas 30 day mortality was similar ( IABP 45 % vs. VAD 43 % , log-rank , P=0.86 ) . CONCLUSION Haemodynamic and metabolic parameters can be reversed more effectively by VAD than by st and ard treatment with IABP . However , more complications were encountered by the highly invasive procedure and by the extracorporeal support OBJECTIVES We sought to examine the use , complications and outcomes with early intraaortic balloon counterpulsation ( IABP ) in patients presenting with cardiogenic shock complicating acute myocardial infa rct ion and treated with thrombolytic therapy . BACKGROUND The use of IABP in patients with cardiogenic shock is widely accepted ; however , there is a paucity of information on the use of this technique in patients with cardiogenic shock who are treated with thrombolytic therapy . METHODS Patients who presented within 6 h of chest pain onset were r and omized to one of four thrombolytic regimens . Cardiogenic shock was not an exclusion criterion , and data for these patients were prospect ively collected . Patients presenting with shock were classified into early IABP ( insertion within one calendar day of enrollment ) or no IABP ( insertion on or after day 2 or never ) . RESULTS There were 68 ( 22 % ) IABP placements in 310 patients presenting with shock . Early IABP use occurred in 62 patients ( 20 % ) and none in 248 ( 80 % ) . Most IABP use occurred in the United States ( 59 of 68 IABP placements ) involving 32 % of U.S. patients presenting with shock . Despite more adverse events in the early IABP group and more episodes of moderate bleeding , this cohort showed a trend toward lower 30-day and 1-year mortality rates . CONCLUSIONS IABP appears to be underutilized in patients presenting with cardiogenic shock , both within and outside the United States . Early IABP institution is associated with an increased risk of bleeding and adverse events but a trend toward lower 30-day and 1-year all-cause mortality BACKGROUND Little evidence is available on the optimal sequence of intra-aortic balloon pump ( IABP ) support initiation and primary percutaneous coronary intervention ( PCI ) in patients who present with cardiogenic shock from ST-elevation myocardial infa rct ion ( STEMI ) . The aim of this study was to evaluate the order of IABP insertion and primary PCI and its association with infa rct size and mortality . METHODS A series of 173 consecutive patients admitted with cardiogenic shock from STEMI and treated with primary PCI and IABP between 2000 and 2009 were included . The order of IABP insertion and primary PCI was left at the discretion of the interventional cardiologist . RESULTS All baseline characteristics were similar in patients who first received IABP ( n=87 ) and patients who received IABP directly after PCI ( n=86 ) . In these two groups , cumulative 30-day mortality was 44 % and 37 % respectively ( p=0.39 ) . Median peak serum creatine kinase ( CK ) concentrations were 5692 U/l and 4034 U/l respectively ( p=0.048 ) . In multivariable analysis , IABP insertion before PCI was independently associated with higher CK levels ( p=0.046 ) . In patients who survived 30 days , IABP insertion before PCI was not associated with late mortality evaluated at five years of follow-up ( HR1.5 , 95 % CI 0.7 - 3.3 ; p=0.34 ) . CONCLUSIONS Early IABP insertion before primary PCI might be associated with higher peak CK levels , indicating a larger infa rct size . A possible explanation may be the increased reperfusion delay . Our study suggests that early reperfusion could have priority over routine early IABP insertion in STEMI patients with cardiogenic shock . R and omized studies are needed to determine the optimal timing of IABP insertion relative to primary PCI BACKGROUND Beneficial effects of preoperative intraaortic balloon pump ( IABP ) treatment , on outcome and cost , in high-risk patients who have coronary artery bypass grafting have been demonstrated . We conducted a prospect i ve , r and omized study to determine the optimal timing for preoperative IABP support in a cohort of high-risk patients . METHODS Sixty consecutive high-risk patients who had coronary artery bypass grafting ( presenting with two or more of the following criteria : left ventricular ejection fraction less than 0.30 , unstable angina , reoperation , or left main stenosis greater than 70 % ) entered the study . Thirty patients did not receive preoperative IABP ( controls ) , 30 patients had preoperative IABP therapy starting 2 hours ( T2 ) , 12 hours ( T12 ) , or 24 hours ( T24 ) , by r and om assignment , before the operation . Fifty patients had preoperative left ventricular ejection fraction mean , less than 0.30 ( less than 0.26+/-0.08 ) , ( n = 40 ) unstable angina , 28 % ( n = 17 ) left main stenosis , and 32 % ( n = 19 ) were reoperations . RESULTS Cardiopulmonary bypass was shorter in the IABP groups . There was one death in the IABP group and six in the control group . The complication rate for IABP was 8.3 % ( n = 5 ) without group differences . Cardiac index was significantly higher postoperatively ( p<0.001 ) in patients with preoperative IABP treatment compared with controls . There were no significant differences between the three IABP subgroups at any time . The incidence of postoperative low cardiac output was significantly lower in the IABP groups ( p<0.001 ) . Intubation time , length of stay in the intensive care unit and the hospital was shorter in the IABP groups ( p = 0.211 , p<0.001 , and p = 0.002 , respectively ) . There were no differences between the IABP subgroups in any of the studied variables . CONCLUSIONS The beneficial effect of preoperative IABP in high-risk patients who have coronary artery bypass grafting was confirmed . There were no differences in outcome between the subgroups ; therefore , at 2 hours preoperatively , IABP therapy can be started BACKGROUND To evaluate the efficacy of prolonged intra-aortic balloon pumping ( IABP ) support in patients with cardiogenic shock following acute myocardial infa rct ion ( AMI ) . MATERIAL / METHODS Thirty-nine patients with cardiogenic shock after AMI were treated with percutaneous coronary intervention which was supported by IABP . After 72 hours of IABP , the patients who attained the criteria of IABP withdrawal were r and omly divided into two groups . The control group ceased IABP whereas the study group continued IABP for additional seven days . RESULTS After IABP , mean arterial pressure , cardiac index , left ventricle ejection fraction and arterial oxygen saturation were significantly elevated in all patients whereas pulmonary capillary wedge pressure and heart rate were decreased . The improvement of cardiac index , left ventricular ejection fraction and pulmonary capillary wedge pressure in the study group was greater than the control group ( P<0.05 ) . After 12-month follow-up , the 6-min walking test and left ventricular ejection fraction in the study group were significantly higher than those of the control group ( P<0.05 ) . No significant differences were noted between the two groups in the incidence ventricular aneurysm and mortality rate . CONCLUSIONS Prolonged use of IABP for up to 10 days offers additional long term benefit in left ventricular function and exercise tolerance BACKGROUND In current guidelines , intraaortic balloon pumping ( IABP ) is considered a class 1 indication in cardiogenic shock complicating acute myocardial infa rct ion . However , evidence is mainly based on retrospective or prospect i ve registries with a lack of r and omized clinical trials . Therefore , IABP is currently only used in 20 % to 40 % of cardiogenic shock cases . The hypothesis of this trial is that IABP in addition to early revascularization by either percutaneous coronary intervention or coronary artery bypass grafting will improve clinical outcome of patients in cardiogenic shock . STUDY DESIGN The IABP-SHOCK II study is a 600-patient , prospect i ve , multicenter , r and omized , open-label , controlled trial . The study is design ed to compare the efficacy and safety of IABP versus optimal medical therapy on the background of early revascularization by either percutaneous coronary intervention or coronary artery bypass grafting . Patients will be r and omized in a 1:1 fashion to 1 of the 2 treatments . The primary efficacy end point of IABP-SHOCK II is 30-day all-cause mortality . Secondary outcome measures , such as hemodynamic , laboratory , and clinical parameters , will serve as surrogate end points for prognosis . Furthermore , an intermediate and long-term follow-up at 6 and 12 months will be performed . Safety will be assessed , by the GUSTO bleeding definition , peripheral ischemic complications , sepsis , and stroke . CONCLUSIONS The IABP-SHOCK II trial addresses important questions regarding the efficacy and safety of IABP in addition to early revascularization in patients with cardiogenic shock complicating myocardial infa rct ion A r and omized prospect i ve clinical trial compared combined treatment with intraaortic balloon pumping and intravenous nitroglycerin for 4 to 5 days with routine clinical management in 20 patients with extensive myocardium at risk for infa rct ion as evidence d by a thallium defect score of 7.0 units or greater . No significant differences in mortality or clinical outcome were observed between the 10 patients receiving the combined treatment and the 10 receiving routine management . In 14 patients two-dimensional echocardiograms obtained 6 to 24 hours after the onset of symptoms and at follow-up 6 to 16 days later ( after completion of combined intraaortic balloon pumping plus nitroglycerin therapy ) were analyzed to determine whether infa rct segment or noninfa rct segment lengths were affected by therapy . Among these 14 patients , 5 ( 3 receiving the combined therapy and 2 receiving routine management ) demonstrated an increase in infa rct segment length of greater than 1.0 cm . Mean infa rct segment length increased 0.30 + /- 0.44 cm in patients receiving the combined therapy and 0.29 + /- 0.36 cm in patients on routine management ( p = NS ) . In contrast , noninfa rct segment length increased greater than 1.0 cm ( mean increase 1.20 + /- 0.39 ) in five of seven patients on routine management but in none of 7 patients receiving intraaortic balloon pumping plus nitroglycerin therapy ( mean decrease 0.22 + /- 0.20 cm ) ( p less than 0.05 ) . No significant differences were noted in left ventricular ejection fraction , as measured by gated blood pool scintigraphy , or thallium perfusion defect score in a comparison of day 1 ( pretreatment ) with day 4 thallium or day 7 to 14 gated blood pool scintigrams . Thus , in patients with extensive myocardium at risk , it is unlikely that a reduction in mortality or a significant improvement in myocardial perfusion or ventricular function can be obtained by early intervention with intraaortic balloon pumping in combination with nitroglycerin . Although this combined therapy failed to prevent infa rct segment lengthening ( infa rct expansion ) , the combined afterload-lowering effects of intraaortic balloon pumping and nitroglycerin did appear to prevent dilation or remodeling of noninfa rct ed segments during the first 2 weeks after acute myocardial infa rct ion OBJECTIVES Using a prospect i ve , r and omized design , we tested our hypothesis that the augmentation of diastolic pressure by intraaortic balloon counterpulsation ( IABP ) would improve the late patency of the occluded coronary artery in patients with early failure of thrombolytic therapy . BACKGROUND Rescue angioplasty is often performed in patients in whom thrombolysis has failed , although 30 % to 60 % of the infa rct -related arteries that are closed early after thrombolytic therapy will open later with conservative therapy . METHODS The study included 45 patients in whom thrombolysis had failed , despite treatment with intravenous tissue-type plasminogen activator ( alteplase 0.75 mg/kg body weight ) delivered over 60 min within 12 h of the onset of symptoms . All patients underwent coronary angiography 60 min after initiation of thrombolytic therapy ( baseline ) , and Thrombolysis in Myocardial Infa rct ion ( TIMI ) grade 0 , 1 or 2 flow was defined as failed thrombolysis . The patients were r and omized to groups receiving IABP for 48 h ( n = 23 ) or conservative therapy ( n = 22 , control subjects ) at the end of cardiac catheterization . The late patency of the infa rct -related artery , the primary end point of the study , was evaluated 3 weeks after myocardial infa rct ion . Stenosis of the infa rct -related artery was measured using a computer-assisted quantitative angiographic system in blinded manner . Data are expressed as mean value + /- SEM . RESULTS There was no difference with regard to the baseline value for TIMI flow grade between the groups . However , 3 weeks after myocardial infa rct ion , the patients treated with IABP had a significantly higher frequency of TIMI flow grade 3 , lower residual percent stenosis and larger minimal lumen diameter of the infa rct -related artery than did the control subjects ( 74 % vs. 32 % , p < 0.05 ; 42 + /- 5 % vs. 68 + /- 6 % , p < 0.01 ; and 1.6 + /- 0.1 vs. 0.9 + /- 0.2 mm , p < 0.01 , respectively ) . CONCLUSIONS These findings suggest that in patients with early failure of thrombolytic therapy , IABP may improve late patency of the occluded coronary artery , probably due to augmented perfusion pressure In this prospect i ve trial the results of preoperative and intraoperative IABP in coronary artery bypass graft ( CABG ) patients with low left ventricular ejection fraction ( LVEF ) were compared . Sixty CABG patients with preoperative LVEF ≤0.30 were enrolled : in group A patients ( n=30 ) IABP was started within 2 hours preoperatively ; in group B ( n=30 ) it was instituted intraoperatively before weaning from cardiopulmonary bypass . Cardiac performance was assessed through Swan-Ganz catheter monitoring and daily echocardiography . Hospital survival , length of IABP support , intubation , ICU and hospital stay , need for postoperative inotropic drugs and incidence of myocardial infa rct ion were compared between the two groups . Survival in group A patients proved significantly higher ( P=0.047 ) . Cardiac performance after myocardial revascularization improved in both groups with significantly better outcomes in group A patients ( p<0.001 ) . Doses of inotropic drugs ( dobutamine , enoximone ) were lower in group A ( P=0.001 ; P=0.004 ) and duration shorter ( p<0.001 ; p<0.001 ) . No major IABP-related complication was observed BACKGROUND Use of aggressive and invasive interventions is more common in the USA than in other countries . We have compared use of re sources for patients with cardiogenic shock after myocardial infa rct ion in the USA and in other countries , and assessed the association between use of re sources and clinical outcomes . METHODS We analysed data for patients with cardiogenic shock after myocardial infa rct ion who were enrolled in the GUSTO-I trial ( 1891 treated in the USA , 1081 treated in other countries ) . Patients were r and omly assigned combinations of streptokinase , heparin , and accelerated tissue-plasminogen activator ( t-PA ) , then decisions about further interventions were left to the discretion of the attending physician . The interventions included in our analysis were : pulmonary-artery catheterisation , cardiac catheterisation , intravenous inotropic agents , ventilatory support , intra-aortic balloon counterpulsation ( IABP ) , percutaneous transluminal coronary angioplasty ( PTCA ) , and coronary bypass graft surgery ( CABG ) . The primary outcome measure was death from any cause at 30 days of follow-up . FINDINGS Patients who were treated in the USA were significantly younger than those treated elsewhere ( median 68 [ IQR 59 - 75 ] vs 70 [ 62 - 76 ] , p < 0.001 ) , a smaller proportion had anterior infa rct ion ( 49 vs 53 % , p < 0.001 ) , and they had a shorter time to treatment ( mean 3.1 vs 3.3 h , p < 0.001 ) . Aggressive diagnostic and therapeutic procedures were used more commonly in the USA than in the other countries : cardiac catheterisation ( 58 vs 23 % ) ; IABP ( 35 vs 7 % ) ; right-heart catheterisation ( 57 vs 22 % ) ; and ventilatory support ( 54 vs 38 % ) . 483 ( 26 % ) of the patients treated in the USA underwent PTCA , compared with 82 ( 8 % ) patients in other countries . Patients who underwent revascularisation had better survival in all countries . Adjusted 30-day mortality was significantly lower among patients treated in the USA than among those treated elsewhere ( 50 vs 66 % , p < 0.001 ) . The difference in mortality remained at 1 year-56 % of patients treated in the USA died versus 70 % of patients treated elsewhere ( hazard ratio 0.69 [ 95 % CI 0.63 - 0.75 ] , p < 0.001 ) . INTERPRETATION 30-day and 1-year mortality was significantly lower among patients treated in the USA than among those treated in other countries . This difference in mortality may be due to the greater use of invasive diagnostic and therapeutic interventions in the USA AIMS The intra-aortic balloon pump ( IABP ) is recommended by current guidelines as adjunct in patients with cardiogenic shock , despite the lack of larger clinical trials . We sought to investigate the use and impact on mortality of IABP in current practice of percutaneous coronary interventions in Europe . METHODS AND RESULTS Between May 2005 and April 2008 a total of 47,407 consecutive patients undergoing percutaneous coronary intervention ( PCI ) in 176 centres in 33 countries in Europe and the Mediterranean basin were enrolled into the registry . From these , 8,102 had ST-elevation myocardial infa rct ion and 7,999 non-ST elevation myocardial infa rct ion and cardiogenic shock was observed in 7.9 % and 2.1 % , respectively . Of the 653 patients with cardiogenic shock 25 % were treated with an IABP . In-hospital mortality , with and without IABP , was 56.9 % and 36.1 % . In the multivariate analysis the use of IABP was not associated with an improved survival ( odds ratio 1.47 ; 95 % CI 0.97 - 2.21 , p=0.07 ) . CONCLUSIONS In current clinical practice in Europe , IABP is used only in one quarter of patients with cardiogenic shock treated with primary PCI . However , there was no hint of a beneficial effect of IABP on outcome . Therefore , a large r and omised clinical trial is urgently needed to define the role of IABP in patients with PCI for shock Aims The recommendation for the use of the intra-aortic balloon pump ( IABP ) as adjunct in patients with cardiogenic shock undergoing primary PCI in current guidelines is controversial . We sought to investigate the use and impact of the outcome of IABP in current practice of percutaneous coronary interventions in Germany . Methods and results Between January 2006 and December 2011 , a total of 55,008 consecutive patients with acute coronary syndromes undergoing PCI in 41 hospitals were enrolled into the prospect i ve Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte registry . Of these , 22,039 had STEMI and 32,969 had NSTEMI , and cardiogenic shock was observed in 1,435 ( 6.5 % ) and 478 ( 1.4 % ) , respectively . Of the total of 1,913 patients with shock , 487 ( 25.5 % ) were treated with IABP . In-hospital mortality with and without IABP was 43.5 and 37.4 % . In the multivariate analysis , the use of IABP was associated with a strong trend for an increased mortality ( odds ratio 1.45 , 95 % CI 1.15–1.84 ) . Conclusion In the current clinical practice in Germany , IABP is used only in one quarter of patients with cardiogenic shock treated with primary PCI . We observed no benefit of IABP on outcome , which supports the findings of the r and omized IABP-Shock II trial AIM Intra-aortic balloon pump ( IABP ) therapy before open heart surgery has been suggested for ' ' high risk ' ' patients . METHODS Records from patients undergoing open heart surgery at our institution between June 1999 and February 2002 were review ed . Indication for IABP insertion was severely impaired left ventricular function , acute myocardial infa rct ion ( MI ) or unstable angina . RESULTS Fifty-five patients were included in the study : 41 male , 14 female , age 64+/-9 years . Fifty-one ( 92.7 % ) required coronary artery bypass brafting ( CABG ) alone or as a combined procedure , 2 ( 3.6 % ) required mitral valve surgery , and 2 ( 3.6 % ) needed more complex cardiac procedures . Thirty-two patients ( 58 % ) underwent emergency cardiac surgery and 11 patients ( 20 % ) suffered from acute preoperative MI . The overall 30 days mortality was 9 % . Mean intensive care unit ( ICU ) stay was 6+/-8 days . Four patients ( 7.2 % ) developed postoperative renal failure requiring temporary hemodialysis . Three patients ( 5.4 % ) developed IABP related peripheral vascular complications . CONCLUSIONS Perioperative morbidity and mortality is increased despite preoperative IABP , particularly in patients with acute MI . In contrast to studies not using this approach , preoperative IABP reduces morbidity and mortality of high risk patients . IABP related complications are low . Our data suggest that high risk patients profit from preoperative IABP therapy , however , prospect i ve studies are needed to confirm these findings Poor left-ventricular function , hypertension , and left-ventricular hypertrophy in patients with coronary artery disease ( CAD ) undergoing coronary artery bypass grafting ( CABG ) are associated with increased operative risks . Between June 1994 and March 1996 , 33 patients undergoing CABG , were r and omized into 2 groups . One group ( IABP group , n = 19 ) received IABP treatment on average for 2 hours prior to CPB , the other group ( control group , n = 14 ) had no preoperative IABP , Cardiac performance was measured pre- and postoperatively by Swan-Ganz catheter . Mean age was 65 years and 90 % were men . All patients had a preoperative LVEF < or = 40 % ( mean 32.6 + /- 11.1 % ) , 3-vessel disease , established hypertension ( WHO criteria ) , and LV hypertrophy ( ventricular mass > or = 136 g/m2 [ men ] or > or = 110 g/m2 [ women ] ) . Ischemia time was similar in both groups while CPB-time was shorter in the IABP group , p < 0.05 . There were no hospital deaths in the IABP group , but 3 in the control group suffered postoperative low cardiac output . Nine patients ( 64 % ) in the control group required IABP support postoperatively , but only 20 % of the patients in the IABP group had a shorter ICU stay , 2.4 + /- 0.9 vs. 3.4 + /- 1.1 days , p < 0.01 . Cardiac index increased significantly in the IABP group prior to CPB and was higher compared to control , p < 0.001 . Five min after CBP cardiac index was higher in the IABP group than in the control group , p = 0.013 , and continued to increase thereafter , while no further improvement was observed in controls . Preoperative IABP treatment in hypertensive patients with CAD , low LVEF and LV hypertrophy who are undergoing CABG is beneficial . An improved cardiac performance pre- and postoperatively was associated with a lower rate of hospital mortality and less postoperative morbidity , as well as shorter ICU stay . The treatment is cost-beneficial This study compared the hemodynamic effects of enhanced external counterpulsation and intra-aortic counterpulsation in patients with acute myocardial infa rct ion . Results demonstrated similarity between these 2 methods , except enhanced external counterpulsation had a transient effect of increasing right atrial pressure , pulmonary capillary wedge pressure , and cardiac index CONTEXT Cardiogenic shock ( CS ) is the leading cause of death for patients hospitalized with acute myocardial infa rct ion ( AMI ) . OBJECTIVE To assess the effect of early revascularization ( ERV ) on 1-year survival for patients with AMI complicated by CS . DESIGN The SHOCK ( Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock ) Trial , an unblinded , r and omized controlled trial from April 1993 through November 1998 . SETTING Thirty-six referral centers with angioplasty and cardiac surgery facilities . PATIENTS Three hundred two patients with AMI and CS due to predominant left ventricular failure who met specified clinical and hemodynamic criteria . INTERVENTIONS Patients were r and omly assigned to an initial medical stabilization ( IMS ; n = 150 ) group , which included thrombolysis ( 63 % of patients ) , intra-aortic balloon counterpulsation ( 86 % ) , and subsequent revascularization ( 25 % ) , or to an ERV group ( n = 152 ) , which m and ated revascularization within 6 hours of r and omization and included angioplasty ( 55 % ) and coronary artery bypass graft surgery ( 38 % ) . MAIN OUTCOME MEASURES All-cause mortality and functional status at 1 year , compared between the ERV and IMS groups . RESULTS One-year survival was 46.7 % for patients in the ERV group compared with 33.6 % in the IMS group ( absolute difference in survival , 13.2 % ; 95 % confidence interval [ CI ] , 2.2%-24.1 % ; P<.03 ; relative risk for death , 0.72 ; 95 % CI , 0.54 - 0.95 ) . Of the 10 prespecified subgroup analyses , only age ( < 75 vs > /= 75 years ) interacted significantly ( P<.03 ) with treatment in that treatment benefit was apparent only for patients younger than 75 years ( 51.6 % survival in ERV group vs 33.3 % in IMS group ) . Eighty-three percent of 1-year survivors ( 85 % of ERV group and 80 % of IMS group ) were in New York Heart Association class I or II . CONCLUSIONS For patients with AMI complicated by CS , ERV result ed in improved 1-year survival . We recommend rapid transfer of patients with AMI complicated by CS , particularly those younger than 75 years , to medical centers capable of providing early angiography and revascularization procedures Intraaortic balloon counterpulsation ( IABP ) has been shown to improve coronary artery patency and reduce the rates of recurrent myocardial ischemia and its sequelae in selected patients when used within 24 hours of acute myocardial infa rct ion . The economic implication s of prophylactic IABP use are unknown . We obtained hospital bills for 102 patients enrolled in the R and omized IABP Trial ( 56 % ) and converted charges to costs using each hospital 's Medicare cost report . In-hospital costs for patients who had 48 hours of IABP were compared with those of patients who did not . The costs of angiographic and clinical complications were determined . Small differences in clinical and angiographic characteristics existed between patients in the economic sub study and the overall population , but overall angiographic and clinical outcomes were comparable . Costs for patients who had IABP versus control patients were similar : mean $ 22,357 + /- $ 14,369 versus $ 19,211 + /- $ 8,414 , median ( 25th and 75th percentiles ) $ 17,903 ( $ 15,787 , $ 22,147 ) versus $ 17,913 ( $ 15,144 , $ 21,433 ) , p = 0.45 . Hospital costs were higher with the development of recurrent ischemia : mean $ 23,125 + /- $ 7,690 versus $ 20,416 + /- $ 12,449 , median $ 21,069 ( $ 17,896 , $ 26,885 ) versus $ 17,492 ( $ 14,892 , $ 20,998 ) p = 0.02 . Patients who had an adverse clinical event ( death , stroke , reinfa rct ion , and emergency revascularization ) also had higher hospital costs : mean $ 25,598 + /- $ 10,024 versus $ 19,790 + /- $ 12,045 , median $ 21,877 ( $ 18,380 , $ 28,049 ) versus $ 17,364 ( $ 14,773 , $ 20,779 ) , p = 0.002 . The prophylactic use of IABP in patients at high risk of infa rct artery reocclusion within 24 hours of acute myocardial infa rct ion provides sustained clinical benefit without substantially increasing hospital costs BACKGROUND High-risk patients would benefit the most of OPCAB revascularization . This prospect i ve and r and omized study evaluates the efficacy and safety of pre- and perioperative IABC in high-risk OPCAB . MATERIAL Group A-IABC started prior to induction of anesthesia ( n = 15 ) ; group B-no preoperative IABC ( n = 15 ) . Adult high-risk coronary patients to undergo OPCAB . High risk = ( minimum 2 ) EF < 0.30 , left main stenosis , unstable angina , redo . Bailout if hemodynamic instability CPB or IABC in group B. Study endpoints ( a ) cardiac protection ( troponin 1 , cardiac index ( CI ) , ECG ) , ( b ) inflammatory response ( lactate , IL-6 ) , ( c ) clinical outcome ( mortality , morbidity ) . Emergency operations 33 % , re-operation 13 % , unstable angina 100 % , left main 60 % and EF 0.29 , without group differences . RESULTS No bailout group A , 10 in group B , p < 0.0001 . Postoperative IABC six ( group A ) and seven patients ( group B ) , during 6.8 + /- 5.1 hours ( group A ) versus 41.2 + /- 25.5 hours ( group B ) , p = 0.0110 . Myocardial protection without group differences , but CI significantly better in group A. Inflammatory response significantly less in group A. CLINICAL OUTCOMES : one death , one MI and two renal failure in group B , none in group A. Intensive care unit ( ICU ) stay 27 + /- 3 hours ( group A ) versus 65 + /- 28 hours ( group B ) , p = 0.0017 . LOS 8 + /- 2 days ( group A ) versus 15 + /- 10 ( group B ) , p = 0.0351 . No IABC related complications . CONCLUSIONS Pre- and perioperative IABC therapy offers efficient hemodynamic support during high-risk OPCAB surgery , lowers the risk of hemodynamic instability , is safe and shortens both ICU and hospital length of stay significantly , and is a cost-effective therapy Background — Although coronary artery bypass grafting is generally preferred in symptomatic patients with severe , complex multivessel , or left main disease , some patients present with clinical features that make coronary artery bypass grafting clinical ly unattractive . Percutaneous coronary intervention with hemodynamic support may be feasible for these patients . Currently , there is no systematic comparative evaluation of hemodynamic support devices for this indication . Methods and Results — We r and omly assigned 452 symptomatic patients with complex 3-vessel disease or unprotected left main coronary artery disease and severely depressed left ventricular function to intra-aortic balloon pump ( IABP ) ( n=226 ) or Impella 2.5 ( n=226 ) support during nonemergent high-risk percutaneous coronary intervention . The primary end point was the 30-day incidence of major adverse events . A 90-day follow-up was required , as well , by protocol . Impella 2.5 provided superior hemodynamic support in comparison with IABP , with maximal decrease in cardiac power output from baseline of −0.04±0.24 W in comparison with −0.14±0.27 W for IABP ( P=0.001 ) . The primary end point ( 30-day major adverse events ) was not statistically different between groups : 35.1 % for Impella 2.5 versus 40.1 % for IABP , P=0.227 in the intent-to-treat population and 34.3 % versus 42.2 % , P=0.092 in the per protocol population . At 90 days , a strong trend toward decreased major adverse events was observed in Impella 2.5–supported patients in comparison with IABP : 40.6 % versus 49.3 % , P=0.066 in the intent-to-treat population and 40.0 % versus 51.0 % , P=0.023 in the per protocol population , respectively . Conclusions — The 30-day incidence of major adverse events was not different for patients with IABP or Impella 2.5 hemodynamic support . However , trends for improved outcomes were observed for Impella 2.5–supported patients at 90 days . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00562016 BACKGROUND Reoperative coronary artery bypass grafting ( redo CABG ) is associated with an increased operative risk compared with primary CABG . Because the hospital mortality in redo CABG is known to be influenced by poor left ventricular function ( left ventricular ejection fraction < or = 0.40 ) , unstable angina , and left main stem stenosis greater than or equal to 70 % , a preoperative intraaortic balloon pump ( IABP ) support could be beneficial to improve the outcome in high-risk redo CABG . METHODS Between June 1994 and October 1996 , 48 high-risk patients underwent redo CABG and were r and omized into the following groups : group 1 ( 24 patients ) who received preoperative IABP treatment on average 2 hours before cardiopulmonary bypass , and group 2 ( 24 patients ) who received no preoperative IABP and served as controls . Mean age was 65 years and 90 % ( 43 patients ) were men . Forty-one patients had preoperative left ventricular ejection fraction less than or equal to 0.40 ( 85 % ) , 38 % ( 18 patients ) had left main stem stenosis greater than or equal to 70 % , and 54 % ( 26 patients ) had unstable angina preoperatively . Preoperative patient characteristics did not differ between the groups . RESULTS The time on cardiopulmonary bypass was shorter in group 1 , 86 versus 110 minutes ( p = 0.006 ) . There were no hospital deaths in group 1 , but four deaths occurred in the control group ( p = 0.049 ) . Cardiac index rose significantly preoperatively after introduction of the IABP in group 1 . Cardiac index was significantly higher postoperatively in group 1 compared with group 2 and remained significantly higher during the first 24 hours after cardiopulmonary bypass . Significantly fewer patients in the IABP group had postoperative low cardiac output ( 4 versus 13 patients ) . Nine patients in group 2 required IABP support postoperatively for 4.1 + /- 1.7 days . Only 2 patients in group 1 needed IABP postoperatively , and their IABPs were successfully removed on the first postoperative day . The preoperative IABP-supported patients had a shorter intensive care unit stay , 2.4 + /- 0.8 days compared with group 2 , 4.5 + /- 2.2 days ( p = 0.007 ) , as well as a shorter hospital stay . The preoperative IABP treatment was found to be cost-effective . CONCLUSIONS Preoperative treatment with IABP in high-risk redo CABG patients is an effective modality to prepare these patients to have their myocardial revascularization in an as nonischemic situation as possible , which result ed in a significantly lower hospital mortality , fewer instances of postoperative low cardiac output , and shorter stays in both the intensive care unit and the hospital OBJECTIVES A large , international , multicenter , prospect i ve , r and omized trial was performed to determine the role of prophylactic intraaortic balloon pump ( IABP ) counterpulsation after primary percutaneous transluminal coronary angioplasty ( PTCA ) in acute myocardial infa rct ion ( AMI ) . BACKGROUND Previous studies have suggested that routine IABP use after primary PTCA reduces infa rct -related artery reocclusion , augments myocardial recovery and improves clinical outcomes . METHODS Cardiac catheterization was performed in 1,100 patients within 12 h of onset of AMI at 34 clinical centers . Clinical and angiographic variables were used to stratify patients undergoing primary PTCA into high and low risk groups . High risk patients were then r and omized to 36 to 48 h of IABP ( n = 211 ) or traditional care ( n = 226 ) . The study had 80 % power to detect a reduction in the primary end point from 30 % to 20 % . RESULTS There was no significant difference in the predefined primary combined end point of death , reinfa rct ion , infa rct -related artery reocclusion , stroke or new-onset heart failure or sustained hypotension in patients treated with an IABP versus those treated conservatively ( 28.9 % vs. 29.2 % , p = 0.95 ) . The IABP strategy conferred modest benefits in reduction of recurrent ischemia ( 13.3 % vs. 19.6 % , p = 0.08 ) and subsequent unscheduled repeat catheterization ( 7.6 % vs. 13.3 % , p = 0.05 ) but did not reduce the rate of infa rct -related artery reocclusion ( 6.7 % vs. 5.5 % , p = 0.64 ) , reinfa rct ion ( 6.2 % vs. 8.0 % , p = 0.46 ) or mortality ( 4.3 % vs. 3.1 % ) and was associated with a higher incidence of stroke ( 2.4 % vs. 0 % , p = 0.03 ) . IABP use did not result in enhanced myocardial recovery as assessed by paired admission to predischarge and 6-week rest and exercise left ventricular ejection fraction . CONCLUSIONS In contrast to previous studies , a prophylactic IABP strategy after primary PTCA in hemodynamically stable high risk patients with AMI does not decrease the rates of infa rct -related artery reocclusion or reinfa rct ion , promote myocardial recovery or improve overall clinical outcome BACKGROUND Preoperative use of intraaortic balloon pumping ( IABP ) has increased in high-risk patients . Linear flow during cardiopulmonary bypass ( CPB ) can induce sub clinical damage , whereas automatic IABP mode may maintain pulsatile flow . We sought to evaluate differences between suspending IABP and switching it to an automatic 80 bpm mode during cardioplegic arrest . METHODS Between January and November 2004 , 40 patients undergoing preoperative IABP were r and omized to receive either st and ard nonpulsatile CPB with IABP discontinued during cardioplegic arrest ( 20 patients ; group A ) or IABP-induced pulsatile ( automatic 80 bpm ) CPB ( 20 patients ; group B ) . Hospital outcome was recorded . Urine output , blood urea nitrogen ( BUN ) , creatine , creatinine clearance , peripheral lactate , recovery of gut motility , alanine-amino-transferase ( ALT ) , aspartate-amino-transferase ( AST ) , lactic dehydrogenase ( LDH ) , bilirubin , and amylase ( AMY ) were compared . RESULTS There were no IABP-related complications , nor perioperative renal or liver failures , nor hospital deaths , nor myocardial infa rct ions . Intensive care and hospital stay , urine output , and recovery of gut motility were comparable . Group B showed lower creatine on the first ( p = 0.01 ) and second ( p = 0.005 ) postoperative days , higher creatinine clearance ( first day : p = 0.01 ; second day : p = 0.03 ) , lower lactate after CPB termination ( p = 0.0001 ) and during the first day ( p = 0.001 ) . The ALT , AST , and AMY were lower in group B ( first day ALT : p = 0.01 ; AST : p = 0.04 ; AMY : p = 0.017 ; second day ALT : p = 0.01 ; AST : p = 0.02 ; AMY : p = 0.027 ) , as well as total bilirubin ( first day : p = 0.05 ; second day : p = 0.02 ) . CONCLUSIONS Automatic 80 bpm IABP during cardioplegic arrest improves creatinine clearance and splanchnic enzymes . There is no reason to suspend preoperative IABP support during cardioplegic arrest Intra-aortic balloon counterpulsation ( IABP ) related complications in a heterogeneous group of patients who received an IABP before or after thrombolytic therapy and mechanical revascularization or in the management of refractory unstable angina and myocardial infa rct ion related mechanical complications were evaluated prospect ively . Ninety-one patients were enrolled to the study . Mean IABP duration was 4.3+/-2.4 days . While the IABP was in place , three patients ( 3.3 % ) had femoral artery emboli , four patients ( 4.4 % ) had lower extremity ischemia that resolved after the removal of the balloon , eight patients ( 8.8 % ) had groin hematoma requiring blood transfusion ( < or = 2 units ) and four patients ( 4.4 % ) had intra-aortic balloon rupture . The relation of several risk factors to groin hematoma requiring < or = 2 units blood transfusion , emboli , lower extremity ischemia and to total complications was evaluated . A chi-squared analysis showed that nadroparine use was more often complicated with emboli ( P = 0.00005 ) and ischemic events ( emboli and /or lower extremity ischemia ) ( three patients ; 30 % of nadroparine group vs. four patients ; 4.9 % of heparin group , P = 0.005 ) and hypercholesterolemia ( > 200 mg/dl ) was more often complicated with lower extremity ischemia ( P = 0.017 ) . Forward conditional logistic regression analysis did not show any relation between the risk factors identified and emboli , lower extremity ischemia , ischemic events and groin hematoma ( P>0.05 ) , but an inverse relation was found between IABP duration and total complications ( P = 0.0198 ) . In conclusion , IABP related complications were found to remain unchanged but were not life-threatening and were inversely related to IABP duration and this suggests shorter periods of IABP use whenever possible and one must be cautious to use low molecular weight heparin in patients with an IABP in place BACKGROUND High sodium intake increases blood pressure , a risk factor for cardiovascular disease , but the effects of sodium intake on global cardiovascular mortality are uncertain . METHODS We collected data from surveys on sodium intake as determined by urinary excretion and diet in persons from 66 countries ( accounting for 74.1 % of adults throughout the world ) , and we used these data to quantify the global consumption of sodium according to age , sex , and country . The effects of sodium on blood pressure , according to age , race , and the presence or absence of hypertension , were calculated from data in a new meta- analysis of 107 r and omized interventions , and the effects of blood pressure on cardiovascular mortality , according to age , were calculated from a meta- analysis of cohorts . Cause-specific mortality was derived from the Global Burden of Disease Study 2010 . Using comparative risk assessment , we estimated the cardiovascular effects of current sodium intake , as compared with a reference intake of 2.0 g of sodium per day , according to age , sex , and country . RESULTS In 2010 , the estimated mean level of global sodium consumption was 3.95 g per day , and regional mean levels ranged from 2.18 to 5.51 g per day . Globally , 1.65 million annual deaths from cardiovascular causes ( 95 % uncertainty interval [ confidence interval ] , 1.10 million to 2.22 million ) were attributed to sodium intake above the reference level ; 61.9 % of these deaths occurred in men and 38.1 % occurred in women . These deaths accounted for nearly 1 of every 10 deaths from cardiovascular causes ( 9.5 % ) . Four of every 5 deaths ( 84.3 % ) occurred in low- and middle-income countries , and 2 of every 5 deaths ( 40.4 % ) were premature ( before 70 years of age ) . The rate of death from cardiovascular causes associated with sodium intake above the reference level was highest in the country of Georgia and lowest in Kenya . CONCLUSIONS In this modeling study , 1.65 million deaths from cardiovascular causes that occurred in 2010 were attributed to sodium consumption above a reference level of 2.0 g per day . ( Funded by the Bill and Melinda Gates Foundation . ) Objectives : Intra-aortic balloon pump ( IABP ) plays a pivotal role in the treatment of cardiogenic shock ( CS ) complicating acute ST-segment elevation myocardial infa rct ion ( STEMI ) . However , the influence of IABP on the inflammatory response has not been well evaluated . We sought to assess the effects of IABP support upon C-reactive protein ( CRP ) levels in patients with STEMI complicated by CS undergoing percutaneous coronary intervention ( PCI ) . Methods : This was a prospect i ve study and a total of 91 patients with STEMI complicated by CS receiving emergency PCI were enrolled , 43 cases of which received IABP support , and the remaining cases without IABP therapy were the control group . CRP levels were determined at admission , and on days 3 and 7 . Troponin I peak , left ventricular function and major adverse cardiovascular events were compared following PCI . Results : The IABP group had lower CRP levels at days 3 and 7 , greater improvement in left ventricular function and lower troponin peak following PCI . Significant differences were also observed in the incidence of mortality at 6-month follow-up , both in hospital and after 30 days . Conclusions : IABP support improves clinical prognosis and attenuates the CRP level in patients with CS complicating STEMI after PCI The value of intraaortic balloon counterpulsation in limiting infa rct size and improving survival was studied in patients with early transmural myocardial infa rct ion complicated by acute heart failure . Thirty such patients , previously well , were r and omly assigned to counterpulsation ( 14 patients ) or st and ard therapy ( 16 patients ) . Counterpulsation was begun 4.8 to 13.7 hours ( mean 7.1 ) after the onset of pain and continued for less than 1 to 11 days ( mean 4.5 ) . Peak creatine kinase was 1,794 + /- 846 IU/liter ( mean + /- st and ard deviation ) in patients receiving counterpulsation compared with 1,688 + /- 908 for those receiving st and ard therapy ; cumulative creatine kinase was 3,590 + /- 1,936 IU/liter for patients receiving counterpulsation and 2,945 + /- 1,803 for those receiving st and ard therapy . Hospital mortality was similar ( counterpulsation , 7 of 14 ; st and ard therapy , 7 of 16 [ p = 0.05 for 25 percent mortality reduction ] ) as was mortality at follow-up ( counterpulsation , 8 of 14 ; st and ard therapy , 10 of 16 [ p = 0.09 for 25 percent mortality reduction ] ) . Functional class at follow-up examination 1 to 36 months ( mean 15 ) after infa rct ion was also similar in the two groups . Counterpulsation did not appear to modify infa rct size or to alter morbidity or mortality when initiated as primary therapy 4.8 to 13.7 hours after the onset of symptoms of myocardial infa rct ion OBJECTIVES The aim of this study was to test whether the left ventricular assist device ( LVAD ) Impella LP2.5 ( Abiomed Europe GmbH , Aachen , Germany ) provides superior hemodynamic support compared with the intra-aortic balloon pump ( IABP ) . BACKGROUND Cardiogenic shock caused by left ventricular failure is associated with high mortality in patients with acute myocardial infa rct ion ( AMI ) . An LVAD may help to bridge patients to recovery from left ventricular failure . METHODS In a prospect i ve , r and omized study , 26 patients with cardiogenic shock were studied . The primary end point was the change of the cardiac index ( CI ) from baseline to 30 min after implantation . Secondary end points included lactic acidosis , hemolysis , and mortality after 30 days . RESULTS In 25 patients the allocated device ( n = 13 IABP , n = 12 Impella LP2.5 ) could be safely placed . One patient died before implantation . The CI after 30 min of support was significantly increased in patients with the Impella LP2.5 compared with patients with IABP ( Impella : DeltaCI = 0.49 + /- 0.46 l/min/m(2 ) ; IABP : DeltaCI = 0.11 + /- 0.31 l/min/m(2 ) ; p = 0.02 ) . Overall 30-day mortality was 46 % in both groups . CONCLUSIONS In patients presenting with cardiogenic shock caused by AMI , the use of a percutaneously placed LVAD ( Impella LP 2.5 ) is feasible and safe , and provides superior hemodynamic support compared with st and ard treatment using an intra-aortic balloon pump . ( Efficacy Study of LV Assist Device to Treat Patients With Cardiogenic Shock [ ISAR-SHOCK ] ; NCT00417378 ) |
1,616 | 28,402,017 | Data for symptom days , night-time awakenings , restricted activities of daily living and school absences were skewed or could not be analysed ; some mean scores were better in the trained group , but most differences between groups were small and did not persist to 24 months .
Schools that received asthma education were more adherent to asthma policies , and staff were better prepared ; more schools that had received staff asthma training had written asthma policies compared with control schools , more intervention schools showed improvement in measures taken to prevent or manage exercise-induced asthma attacks and more staff at intervention schools reported that they felt able to administer salbutamol via a spacer .
Asthma education for school staff increases asthma knowledge and preparedness , but studies vary and all available evidence is of low quality .
Studies have not yet captured whether this improvement in knowledge has led to appreciable benefits over the short term or the longer term for the safety and health of children with asthma in school .
R and omised evidence does not contribute to our knowledge of content or attributes of interventions that lead to the best outcomes , or of re sources required for successful implementation .
This applies to both r and omised and non-r and omised studies , although the latter may be better placed to observe important clinical outcomes such as exacerbations and mortality in the longer term | BACKGROUND Teachers and school staff should be competent in managing asthma in schools .
Demonstrated low levels of asthma knowledge mean that staff may not know how best to protect a child with asthma in their care , or may fail to take appropriate action in the event of a serious attack .
Education about asthma could help to improve this knowledge and lead to better asthma outcomes for children .
OBJECTIVES To assess the effectiveness and safety of asthma education programmes for school staff , and to identify content and attributes underpinning them . | BACKGROUND AND OBJECTIVE : Impoverished urban children suffer disproportionately from asthma and underuse preventive asthma medications . The objective of this study was to examine cost-effectiveness ( CE ) of the School-Based Asthma Therapy ( SBAT ) program compared with usual care ( UC ) . METHODS : The analysis was based on the SBAT trial , including 525 children aged 3 to 10 years attending urban preschool or elementary school who were r and omized to either UC or administration of 1 dose of preventive asthma medication at school by the school nurse each school day . The primary outcome was the mean number of symptom-free days ( SFDs ) . The impact of the intervention on medical costs was estimated by using parent-reported child health services utilization data and average national reimbursement rates . We estimated the cost of running the program using wages for program staff . Productivity costs were estimated by using value of parent lost time due to child illness . CE of the SBAT program compared with UC was evaluated based on the incremental CE ratio . RESULTS : The health benefit of the intervention was equal to ∼158 SFD gained per each 30-day period ( P < .05 ) per 100 children . The programmatic expenses summed to an extra $ 4822 per 100 children per month . The net saving due to the intervention ( reduction in medical costs and parental productivity , and improvement in school attendance ) was $ 3240 , result ing in the incremental cost-savings difference of $ 1583 and CE of $ 10 per 1 extra SFD gained . CONCLUSIONS : The SBAT was effective and cost-effective in reducing symptoms in urban children with asthma compared with other existing programs UNLABELLED Teachers and support staff are often called upon to manage asthma at school but may have little knowledge and underst and ing of the condition . The objectives of this study were to develop educational package ( pamphlets ) about asthma , and assess its effectiveness as an educational tool for schools ' staff through evaluation of its impact on the staff 's asthma-related knowledge , attitudes and management practice s on their pupils . A pre-post experimental research design was used in Riyadh city with distribution of self-administered question naires and asthma package to 4 r and omly selected girls schools compounds . Participants were school staff ( n = 297 ) of primary , intermediate and secondary schools . Results showed that only 5.7 % of the staff had received previous training in asthma education . Lack of knowledge and misconceptions about asthma medication were evident among a considerable proportion of the staff specifically for use of antibiotics , steroids , side effect of ventolin , and addicting effect of inhalers . At pretest , only 35 % and 40.1 % of the staff had good level of knowledge and management practice s. At posttest , the corresponding percentages increased significantly to be 83.9 % and 68.6 % respectively . The mean total score of staff 's asthma related-attitudes became more favorable towards asthma education after intervention , it increased significantly from 53.5 to be 55.0 . Total posttest knowledge score was the only predictor of both staff attitudes and management practice s constituting 9.1 % and 10.2 % of their variance . The great majority cited lack of training ( 92 % ) , unavailability school policy ( 86.8 % ) , and shortage of educational re sources ( 88.3 % ) as barriers against asthma education and management in their schools . CONCLUSIONS Most of school staff had poor to fair level of asthma knowledge and management practice s. Such simple educational intervention using pamphlets and demonstration of inhaler use and peaked flow meter was significantly successful in enhancing staff 's asthma-related knowledge , attitudes and management practice s among their pupils . It is very important that training is directed to all staff as pre-service and in-service programs This article describes the evaluation of a comprehensive school-based asthma management program in an inner-city , largely African-American school system . All 54 elementary schools ( combined enrollment 13,247 students ) from a single urban school system participated in this study . Schools were r and omly divided between immediate and delayed intervention programs . The intervention consisted of 3 separate educational programs ( for school faculty/staff , students with asthma , and peers without asthma ) and medical management for the children with asthma ( including an Individual Asthma Action Plan , medications , and peakflow meters ) . Children with asthma were identified using a case detection program and 736 were enrolled into the intervention study . No significant differences were observed in school absences , grade point average , emergency room visits , or hospitalizations between the immediate and delayed intervention groups . Significant increases in knowledge were observed in the immediate intervention group . This study of a school-based asthma management education and medical intervention program did not show any differences between the intervention and control groups on morbidity outcomes . Our experience leads us to believe that such measures are difficult to impact and are not always reliable . Future research ers should be aware of the problems associated with using such measures . In addition , connecting children with a regular source of health care in this population was difficult . More intensive methods of medical management , such as school-based health centers or supervised asthma therapy , might prove more effective in inner-city schools BACKGROUND In Ohio , 14.5 % of 5- to 9-year-olds and 17.3 % of 10- to 17-year-olds have asthma . Moreover , there is concern that these numbers may underestimate the true disease burden . We sought to evaluate variability in asthma rates and respiratory symptoms among central Ohio fourth grade rs as a means to assess potential undiagnosed and undertreated asthma and its determinants . METHODS We recruited 13 central Ohio elementary schools representing a broad range of nonurban setting s and surveyed fourth grade rs to estimate school-level physician-diagnosed asthma ( PDA ) , respiratory morbidity , and home exposures to smoking and pets . We used generalized linear mixed models with r and om intercept for school to examine relationships among exposures , respiratory symptoms , and PDA . RESULTS Across the 13 schools , 94 % of students participated in the survey , and the estimated asthma prevalence rate was 10.2 % ( N = 101 of 987 ) . An additional 41 % reported not having PDA but then went on to report symptoms consistent with asthma potentially suggestive of undiagnosed asthma . Of students with PDA , 21 % reported symptoms suggestive of poorly controlled asthma . High levels of secondh and smoke ( SHS ) exposure were associated both with PDA ( p = .05 ) and with respiratory symptoms ( p < .0001 ) . Students who owned a cat or a bird were more likely to report respiratory symptoms ( p = .02 and p = .04 , respectively ) . CONCLUSIONS We provide evidence that the already high childhood asthma public health burden in central Ohio may be underreported . Schools may be an ideal location to conduct screenings and implement environmental interventions oriented toward SHS and household pets that will yield respiratory morbidity benefits The present study investigated schools as an appropriate context for an intervention design ed to produce clinical and psychological benefits for children with asthma . A total of 193 out of 219 ( 88.1 % ) children with asthma ( aged 7–9 yrs ) from 23 out of 24 ( 95.8 % ) schools completed the study . Intervention schools received a staff asthma-training session , advice on asthma policy , an emergency β2-agonist inhaler with spacer and whole-class asthma workshops . Nonintervention schools received no asthma-related input . Intervention children required less general practitioner-prescribed preventer medication despite no differences in symptom control compared with the nonintervention asthmatic group . Increased peer knowledge of asthma may have mediated improved active quality of life in the intervention group , together with increased self-esteem in young females . Those females not receiving the intervention , but identified as being asthmatic within the classroom , and thus possibly stigmatised , reported decreased self-esteem . Lower self-esteem in young males was associated with pet ownership . No change was found in staff knowledge , the establishment of asthma policies or school absences which were low even before intervention . In conclusion , a whole-school intervention can improve the health of children with asthma when followed with support for all children but effects are likely to be modified by sex and the home environment Objectives . Because children spend a significant proportion of their day in school , pediatric emergencies such as the exacerbation of medical conditions , behavioral crises , and accidental/intentional injuries are likely to occur . Recently , both the American Academy of Pediatrics and the American Heart Association have published guidelines stressing the need for school leaders to establish emergency-response plans to deal with life-threatening medical emergencies in children . The goals include developing an efficient and effective campus-wide communication system for each school with local emergency medical services ( EMS ) ; establishing and practicing a medical emergency-response plan ( MERP ) involving school nurses , physicians , athletic trainers , and the EMS system ; identifying students at risk for life-threatening emergencies and ensuring the presence of individual emergency care plans ; training staff and students in first aid and cardiopulmonary resuscitation ( CPR ) ; equipping the school for potential life-threatening emergencies ; and implementing lay rescuer automated external defibrillator ( AED ) programs . The objective of this study was to use published guidelines by the American Academy of Pediatrics and the American Heart Association to examine the preparedness of schools to respond to pediatric emergencies , including those involving children with special care needs , and potential mass disasters . Methods . A 2-part question naire was mailed to 1000 r and omly selected members of the National Association of School Nurses . The first part included 20 questions focusing on : ( 1 ) the clinical background of the school nurse ( highest level of education , years practicing as a school health provider , CPR training ) ; ( 2 ) demographic features of the school ( student attendance , grade s represented , inner-city or rural/suburban setting , private or public funding , presence of children with special needs ) ; ( 3 ) self-reported frequency of medical and psychiatric emergencies ( most common reported school emergencies encountered over the past school year , weekly number of visits to school nurses , annual number of “ life-threatening ” emergencies requiring activation of EMS ) ; and ( 4 ) the preparedness of schools to manage life-threatening emergencies ( presence of an MERP , presence of emergency care plans for asthmatics , diabetics , and children with special needs , presence of a school nurse during all school hours , CPR training of staff and students , availability of athletic trainers during all athletic events , presence of an MERP for potential mass disasters ) . The second part included 10 clinical scenarios measuring the availability of emergency equipment and the confidence level of the school nurse to manage potential life-threatening emergencies . Results . Of the 675 question naires returned , 573 were eligible for analysis . A majority of responses were from registered nurses who have been practicing for > 5 years in a rural or suburban setting . The most common reported school emergencies were extremity sprains and shortness of breath . Sixty-eight percent ( 391 of 573 [ 95 % confidence interval ( CI ) : 64–72 % ] ) of school nurses have managed a life-threatening emergency requiring EMS activation during the past school year . Eighty-six percent ( 95 % CI : 84–90 % ) of schools have an MERP , although 35 % ( 95 % CI : 31–39 % ) of schools do not practice the plan . Thirteen percent ( 95 % CI : 10–16 % ) of schools do not identify authorized personnel to make emergency medical decisions . When stratified by mean student attendance , school setting , and funding classification , schools with and without an MERP did not differ significantly . Of the 205 schools that do not have a school nurse present on campus during all school hours , 17 % ( 95 % CI : 12–23 % ) do not have an MERP , 17 % ( 95 % CI : 12–23 % ) do not identify an authorized person to make medical decisions when faced with a life-threatening emergency , and 72 % ( 95 % CI : 65–78 % ) do not have an effective campus-wide communication system . CPR training is offered to 76 % ( 95 % CI : 70–81 % ) of the teachers , 68 % ( 95 % CI : 61–74 % ) of the administrative staff , and 28 % ( 95 % CI : 22–35 % ) of the students . School nurses reported the availability of a bronchodilator meter-dosed inhaler ( 78 % [ 95 % CI : 74–81 % ] ) , AED ( 32 % [ 95 % CI : 28–36 % ] ) , and epinephrine autoinjector ( 76 % [ 95 % CI : 68–79 % ] ) in their school . When stratified by inner-city and rural/suburban school setting , the availability of emergency equipment did not differ significantly except for the availability of an oxygen source , which was higher in rural/suburban schools ( 15 % vs 5 % ) . School-nurse responders self-reported more confidence in managing respiratory distress , airway obstruction , profuse bleeding/extremity fracture , anaphylaxis , and shock in a diabetic child and comparatively less confidence in managing cardiac arrest , overdose , seizure , heat illness , and head injury . When analyzing schools with at least 1 child with special care needs , 90 % ( 95 % CI : 86–93 % ) have an MERP , 64 % ( 95 % CI : 58–69 % ) have a nurse available during all school hours , and 32 % ( 95 % CI : 27–38 % ) have an efficient and effective campus-wide communication system linked with EMS . There are no identified authorized personnel to make medical decisions when the school nurse is not present on campus in 12 % ( 95 % CI : 9–16 % ) of the schools with children with special care needs . When analyzing the confidence level of school nurses to respond to common potential life-threatening emergencies in children with special care needs , 67 % ( 95 % CI : 61–72 % ) of school nurses felt confident in managing seizures , 88 % ( 95 % CI : 84–91 % ) felt confident in managing respiratory distress , and 83 % ( 95 % CI : 78–87 % ) felt confident in managing airway obstruction . School nurses reported having the following emergency equipment available in the event of an emergency in a child with special care needs : glucose source ( 94 % [ 95 % CI : 91–96 % ] ) , bronchodilator ( 79 % [ 95 % CI : 74–83 % ] ) , suction ( 22 % [ 95 % CI : 18–27 % ] ) , bag-valve-mask device ( 16 % [ 95 % CI : 12–21 % ] ) , and oxygen ( 12 % [ 95 % CI : 9–16 % ] ) . An MERP design ed specifically for potential mass disasters was present in 418 ( 74 % ) of 573 schools ( 95 % CI : 70–77 % ) . When stratified by mean student attendance , school setting , and funding classification , schools with and without an MERP for mass disasters did not differ significantly . Conclusions . Although schools are in compliance with many of the recommendations for emergency preparedness , specific areas for improvement include practicing the MERP several times per year , linking all areas of the school directly with EMS , identifying authorized personnel to make emergency medical decisions , and increasing the availability of AED in schools . Efforts should be made to increase the education of school nurses in the assessment and management of life-threatening emergencies for which they have less confidence , particularly cardiac arrest , overdose , seizures , heat illness , and head injury Background Within the UK , during September , there is a pronounced increase in the number of unscheduled medical contacts by school-aged children ( 4–16 years ) with asthma . It is thought that that this might be caused by the return back to school after the summer holidays , suddenly mixing with other children again and picking up viruses which could affect their asthma . There is also a drop in the number of prescriptions administered in August . It is possible therefore that children might not be taking their medication as they should during the summer contributing to them becoming ill when they return to school . It is hoped that a simple intervention from the GP to parents of children with asthma at the start of the summer holiday period , highlighting the importance of maintaining asthma medication can help prevent increased asthma exacerbation , and unscheduled NHS appointments , following return to school in September . Methods / design PLEASANT is a cluster r and omised trial . A total of 140 General Practice s ( GPs ) will be recruited into the trial ; 70 GPs r and omised to the intervention and 70 control practice s of “ usual care ” . An average practice is expected to have approximately 100 children ( aged 4–16 with a diagnosis of asthma ) hence observational data will be collected on around 14000 children over a 24-month period . The Clinical Practice Research Data link will collect all data required for the study which includes diagnostic , prescription and referral data . Discussion The trial will assess whether the intervention can reduce exacerbation of asthma and unscheduled medical contacts in school-aged children associated with the return to school after the summer holidays . It has the potential to benefit the health and quality of life of children with asthma while also improving the effectiveness of NHS services by reducing NHS use in one of the busiest months of the year . An exploratory health economic analysis will gauge any cost saving associated with the intervention and subsequent impacts on quality of life . If results for the intervention are positive it is hoped that this could be adopted as part of routine care management of childhood asthma in general practice .Trial registration Current controlled trials : IS RCT N03000938 ( assigned 19/10/12 ) http://www.controlled-trials.com/IS RCT N03000938/.UKCRN ID : This report describes the evaluation of a whole-school intervention to improve morbidity and psychosocial well-being in pupils with asthma . In all , 193 children with asthma ( 7 - 9 years ) from 23 primary /junior schools in the south of Engl and participated . Schools ( n = 12 ) r and omly assigned to the intervention group ( IV ) received a staff asthma training session , advice on asthma policy and practice and an emergency beta(2)-agonist inhaler with spacer . Pupils participated in an asthma lesson . Staff and pupils in non-intervention ( NI ) schools ( n = 11 ) received no asthma-oriented input . While wheeze reports improved for all children with asthma , only the IV group showed lower requirement for medication ( P = 0.01 ) , clinical ly significant improvement ( P < 0.05 ) in activity related quality of life ( QOL ) and increased self-esteem ( SE : social P = 0.01 ; athletic P = 0.05 ; behaviour P = 0.001 ) in girls . SE decreased for NI girls but there was no change for non-asthmatic peers in NI or IV schools which had similar baseline levels of SE and QOL . There was a marginal improvement in the establishment of asthma policies/ practice s and no change in school absence or staff knowledge . The significantly increased peer group underst and ing of asthma seen in the intervention schools may have mediated increased well-being in the IV group . Primary schools are a potentially important context for improving asthma morbidity and psychosocial well-being of children with asthma Background : Up to 17 % of children in the United States have been diagnosed with asthma ; children ages 9 - 14 years experience higher morbidity and mortality compared with other age groups . An academic and counseling program for older elementary students with asthma was developed in collaboration with school personnel , healthcare professionals , and community members : Staying Healthy-Asthma Responsible and Prepared ( SHARP ) . The life span development perspective and the Acceptance of Asthma Model were used to guide development and implementation . Objectives : This study aim ed to establish the preliminary efficacy of SHARP to improve cognitive , behavioral , psychosocial , and quality -of-life outcomes . Methods : A two-group , longitudinal , prospect i ve , cluster r and omized clinical trial design was used . The sample of fourth- to sixth- grade students ( N = 66 ) with asthma aged 9 - 12 years ( M = 10.5 , SD = 0.9 ) was 52 % male , was racially diverse ( 30 % Black , 36 % White , and 18 % biracial ) , and had a wide range of incomes . Three schools ( n = 38 students ) were r and omized to receive SHARP , and two schools ( n = 28 students ) were assigned to usual care . Self-report instruments were used . Results : Compared with the usual care group , statistically significant improvements in the SHARP group were found in student knowledge of asthma , reasoning about asthma , use of risk reduction behaviors , and participation in life activities ( p < .01 , effect sizes > 0.7 ) . Improvements in use of episode management behaviors and acceptance of asthma outcomes were clinical ly significant with medium effect sizes of 0.3 - 0.5 . Discussion : The SHARP Student and Community Components demonstrated preliminary efficacy for improving asthma knowledge , reasoning about asthma , use of episode management and risk reduction behaviors , acceptance of asthma in taking control and vigilance , and participation in life activities OBJECTIVE To test the feasibility and preliminary effectiveness of the School-Based Preventive Asthma Care Technology ( SB-PACT ) program , which includes directly observed therapy of preventive asthma medications in school facilitated by Web-based technology for systematic symptom screening , electronic report generation , and medication authorization from providers . STUDY DESIGN We conducted a pilot r and omized trial of SB-PACT versus usual care with 100 children ( aged 3 - 10 years ) from 19 inner-city schools in Rochester , New York . Outcomes were assessed longitudinally by blinded interviewers . Analyses included bivariate statistics and linear regression models , adjusting for baseline symptoms . RESULTS There were data for 99 subjects for analysis . We screened all children using the Web-based system , and 44 of 49 treatment group children received directly observed therapy as authorized by their providers . Treatment group children received preventive medications 98 % of the time they were in school . Over the school year , children in the treatment group experienced nearly 1 additional symptom-free day over 2 weeks versus the usual care group ( 11.33 vs 10.40 , P = .13 ) . Treatment children also experienced fewer nights with symptoms ( 1.68 vs 2.20 , P = .02 ) , days requiring rescue medications ( 1.66 vs 2.44 , P = .01 ) , and days absent from school due to asthma ( 0.37 vs 0.85 , P = .03 ) compared with usual care . Further , treatment children had a greater decrease in exhaled nitric oxide ( -9.62 vs -0.39 , P = .03 ) , suggesting reduction in airway inflammation . CONCLUSION The SB-PACT intervention demonstrated feasibility and improved outcomes across multiple measures in this pilot study . Future work will focus on further integration of preventive care delivery across community and primary care systems OBJECTIVE To describe and test the feasibility of asthma self-management for adolescents with undiagnosed asthma ( ASMA-Undx ) , an 8-week school-based intervention for urban adolescents comprised of three group and five individual coaching sessions , and academic detailing for their primary care providers ( PCPs ) . METHODS Thirty high school students ( mean age 15.9 ; 92 % female ; 72 % Latino/a ) who reported symptoms of persistent asthma , but no diagnosis were r and omized to ASMA-Undx or a no-treatment control group . Interviews were conducted pre- and post-intervention . RESULTS All intervention students participated in the three group sessions ; 64 % received all five individual coaching sessions . Academic detailing telephone calls made by a pediatric pulmonologist reached 83 % of the students ' PCPs . Relative to controls , a significantly greater proportion of ASMA-Undx students were diagnosed ( 79 % versus 6 % , respectively ) , and prescribed asthma medication ( 57 % versus 6 % , respectively ) . Barriers to diagnosis and treatment included students ' and parents ' lack of knowledge about asthma . CONCLUSION ASMA-Undx is a feasible and promising intervention to assist urban adolescents with undiagnosed asthma obtain a diagnosis and treatment . PRACTICE IMPLICATION S ASMA-Undx has the potential to reach many adolescents because it is school-based . It can serve as a model for interventions targeting other pediatric illnesses The Newcastle Asthma Knowledge question naire was used to determine primary schoolteachers ' knowledge of asthma . The mean score achieved ( 20.71 ± 3.20 ) , was representative of a reasonable degree of knowledge . However , knowledge of symptoms associated with asthma and of medications used to manage the condition was poor . Teachers who had contact with an asthmatic individual or who had received previous training on asthma had a significantly greater knowledge of asthma . An asthma training session , delivered by a pharmacist , was found to significantly improve primary schoolteachers ' knowledge of the condition , however , the extent of the improvement was low Our objective was to determine whether an asthma education program in schools would have 1 ) a direct impact on student knowledge and attitudes to asthma and quality of life of the students with asthma , 2 ) an indirect impact on teacher knowledge and attitudes to asthma and on school policies about asthma , and 3 ) a sustainable program after the re sources to implement the research were withdrawn . Seventeen intervention and 15 control schools participated in a controlled trial . Baseline knowledge and attitudes were measured in year 8 students ( ages 13 - 14 years ) and their teachers together with quality of life in the students with asthma . A three-lesson package about asthma was delivered by teachers as part of the Personal Development/Health/Physical Education ( PD/H/PE ) curriculum . Follow-up question naires were administered to students and staff . Efforts to change school policies were documented . Five years after the intervention , PD/H/PE teachers were contacted to determine whether the program was still operating . Main outcome measures included asthma knowledge , attitudes , and quality of life . Question naires were returned by 4,161/4,475 of the year 8 students at baseline and by 3,443 at follow-up . In intervention schools , compared with control schools , students showed improved asthma knowledge ( P < 0.0001 ) , improvement in tolerance to asthma ( P = 0.02 ) , internal control ( P = 0.03 ) , and less tendency to believe in the role of chance in asthma control ( P = 0.04 ) . Students from intervention but not control schools showed significant improvements in overall quality of life ( P = 0.003 vs. P = 0.82 , respectively ) . Teachers from intervention schools showed significant increases in knowledge compared to control schools ( P < 0.0001 ) . Intervention schools were more likely to seek further health education about asthma ( P < 0.01 ) . Five years after the 35 schools involved in the development of the material s or the trial had been offered the Living With Asthma package , 25 ( 71 % ) were still teaching the program to most or all of their students . Fifty-nine of the 61 ( 97 % ) high schools in the Hunter Region now have the program . Management and distribution of the Living With Asthma program have been taken over by the Asthma Foundation of New South Wales . The package has been up date d and is being offered to all high schools throughout New South Wales as part of the National Asthma-Friendly Schools Project . In conclusion , a teacher-led asthma education program in secondary school had direct and indirect beneficial outcomes and was sustained at a high level for 5 years in most schools in the Hunter Region , despite minimal ongoing maintenance and support from health workers STUDY OBJECTIVE This study assessed the impact of a comprehensive school-based asthma program on symptoms , grade s , and school absences in children , and parents ' asthma management practice s. DESIGN R and omized controlled trial . SETTING Fourteen elementary schools in low-income neighborhoods in Detroit , MI . PARTICIPANTS Eight hundred thirty-five children with asthma in grade s 2 through 5 and their parents . INTERVENTION The intervention entailed six components for children , their parents , classmates , and school personnel to encourage and enable disease management . MEASUREMENTS AND RESULTS Parents completed telephone interviews and the schools provided data at baseline and 24 months after intervention . At follow-up , treatment children with persistent disease had significant declines in both daytime ( 14 % fewer , p < 0.0001 ) and nighttime ( 14 % fewer , p < 0.0001 ) symptoms . Among children with both mild intermittent and persistent disease , those in the treatment group had 17 % fewer daytime symptoms ( p < 0.0001 ) but 40 % more nighttime symptoms . Treatment children had higher grade s for science ( p < 0.02 ) but not reading , mathematics , or physical education . No differences in school absences for all causes between groups were noted in school records . However , parents of treatment group children reported fewer absences attributable to asthma in the previous 3 months ( 34 % fewer , p < 0.0001 ) and 12 months ( 8 % fewer , p < 0.05 ) . Parents of treatment children had higher scores ( 2.19 greater , p = 0.02 ) on an asthma management index . The program may have stimulated attention to symptoms at night by parents of children with mild intermittent disease . Overall , the intervention provided significant benefits , particularly for children with persistent asthma PURPOSE The purpose of this study was to evaluate the effectiveness of the academic asthma education and counseling Staying Healthy-Asthma Responsible and Prepared ™ ( SHARP ) program on fostering psychosocial acceptance of asthma . DESIGN AND METHODS This was a phase III , two-group , cluster-r and omized , single-blinded , longitudinal study . Students from grade s 4 and 5 ( N = 205 ) with asthma and their caregivers completed surveys at pre-intervention and at 1- , 12- , and 24-months post-intervention . Analysis involved multilevel modeling . RESULTS All students demonstrated significant improvement in aspects of acceptance ; students in SHARP demonstrated significant improvement in openness to sharing and connectedness with teachers over students in the control condition . PRACTICE IMPLICATION S The SHARP program offers a well-tested , effective program for psychosocial acceptance of asthma , which is welcomed by schools The purpose of this study was to examine the effect of an asthma education program on schoolteachers ’ knowledge . Pre-test – post-test experimental r and omized controlled design was used . A multistage-cluster sampling technique was used to r and omly select governorate , primary schools , and schoolteachers . Schoolteachers were r and omly assigned either to the experimental group ( n = 36 ) and attended three educational sessions or to the control group ( n = 38 ) who did not receive any intervention . Knowledge about asthma was measured using the Asthma General Knowledge Question naire for Adults ( AGKQA ) . The results indicated that teachers in the experimental group showed significantly ( p < .001 ) higher knowledge of asthma in the first post-test and the second post-test compared with those in the control group . Implementing asthma education enhanced schoolteachers ’ knowledge of asthma . The asthma education program should target schoolteachers to improve knowledge about asthma OBJECTIVE To assess whether information about asthma acquired by individual teachers , following attendance at an inservice seminar , would be communicated to other school staff , and whether policies about asthma management would be subsequently developed in schools . METHODOLOGY A telephone interview was conducted of 50 primary school teachers in the Hunter Region who were selected r and omly from those who had represented their school at an inservice seminar about asthma . RESULTS All 48 respondents had provided feedback to their colleagues , mostly at a staff meeting . After the seminar the number of schools with a written policy about the management of asthma had increased from 1 to 20 . Initially the school 's first aid kits contained a bronchodilator inhaler in 25 schools ( increasing to 43 after the seminar ) , a spacer device in six schools ( increasing to 47 ) and written guidelines for management of an asthma attack in seven schools ( increasing to 32 ) . Teachers from four schools indicated that all school staff knew how to recognize an acute attack prior to the seminar compared with 22 schools afterwards . Before the seminar 18 schools asked parents to supply written instructions for the management of their children at school but this increased to 44 after the seminar . CONCLUSIONS A programme of one-off seminars attended by one teacher from each primary school result ed in large increases in the proportion of schools with appropriate policies for the management of asthma in the school environment OBJECTIVE . Children with asthma spend a large portion of their day in school , and the extent to which public schools are prepared to meet their health needs is an important issue . The objective of this study was to identify asthma policies and practice s in rural and urban school setting s and to compare them with current National Heart , Lung , and Blood Institute recommendations . METHODS . A stratified r and om sample of school nurses who represented each of the 500 active Pennsylvania school districts were surveyed in 2004 concerning nurse staffing patterns , availability of asthma monitoring and treatment-related equipment , emergency preparedness , availability of asthma-related support and case management services , school-specific procedures including identification of children with asthma and accessibility of inhaler medication during school hours , presence and content of written asthma management plans , and perceived obstacles to asthma management in the school setting . Sampling weights were incorporated into the analyses to take the survey design into account . RESULTS . The overall response rate was 76 % , with a total of 757 surveys analyzed . In more than half of secondary schools and three quarters of elementary schools , nurses were present < 40 hours per week . Nearly 1 in 5 schools reported that staff who know what to do for a severe asthma attack were not always available . In 72 % of rural schools , children were allowed to self-carry rescue inhalers , as compared with 47 % of urban schools . Asthma management plans were on file for only 1 quarter of children with asthma , and important information often was omitted . Approximately half of the schools were equipped with peak flow meters and nebulizers , and spacers were available in 1 third of schools . CONCLUSIONS . Improvements are needed to bring schools into compliance with current recommendations , including more consistent availability of knowledgeable staff , improved access to asthma monitoring and treatment-related equipment , more universal use of asthma management plans , and greater access to inhalers while at school , including increasing the proportion of children who are allowed to carry and self-administer inhaler medication The Healthy Learners Asthma Initiative ( HLAI ) involved collaboration between Minneapolis Public Schools ( MPS ) , local health care providers/payors , parents , and other partners . The intervention included development of enhanced asthma care in school health offices and clinic performance improvement projects to foster adoption of National Institutes of Health asthma guidelines . Goals were to improve asthma management among school children and reduce asthma-related school absences , hospitalizations , and emergency department visits . The effectiveness evaluation utilized a r and omized community trial design with 16 elementary and middle schools matched and r and omly assigned to either an intervention or a control group . Outcomes investigated were ( a ) school health office impacts and ( b ) school attendance . Data sources included school health office records , district attendance , enrollment , and demographics files . Following implementation of the HLAI , asthma visits to health offices were significantly lower in intervention schools compared to control schools ( 91 vs 121 visits per 100 students with asthma per month ) , and intervention schools had greater availability of medication and asthma action plans and more peakflow measurements , asthma education , and parent communication . Clinics initiated significantly more asthma action plans and sent them to MPS . Attendance differences between groups were limited to students who received asthma care through the school health office . Monitoring of asthma management activities provided through school health offices from 2002 to 2005 indicates sustained implementation of enhanced asthma care in schools and increased asthma communication between school , parents , and health care providers BACKGROUND Adolescents with asthma are at risk for psychological and behavioral problems . The aim of this study was to determine whether high school students with asthma are at increased risk for bullying in school and cyberspace , and to explore the role of depressive symptoms in moderating this association . METHODS A secondary data analysis was completed with the 2011 Florida Youth Risk Behavior Survey . Participant included a r and om sample of adolescents in grade s 9 through 12 who attended public high schools in Florida . Descriptive and inferential statistics were conducted using SPSS software . RESULTS We examined data from 6212 high school adolescents and found a significant relationship between current asthma and cyberbullying in adolescents . Of the sample diagnosed with asthma , 15.6 % reported bullying and 17 % cyberbullying ( versus 10.2 % and 11 % of nonasthmatics ) . We further examined data using depressive symptoms as a mediating and moderating variable and found significance on all accounts . CONCLUSIONS Adolescents with asthma are at increased risk for being victims of bullying in school and cyberspace . Our findings suggest that adolescents with asthma who also report depressive symptoms are particularly at high risk for bullying than adolescents with asthma who did not report depressive symptoms . Efforts to increase education and decrease all types of bullying at the high school level for both students with and without asthma are warranted RATIONALE Asthma prevalence and morbidity are especially elevated in adolescents , yet few interventions target this population . OBJECTIVES To test the efficacy of Asthma Self-Management for Adolescents ( ASMA ) , a school-based intervention for adolescents and medical providers . METHODS Three hundred forty-five primarily Latino/a ( 46 % ) and African American ( 31 % ) high school students ( mean age = 15.1 yr ; 70 % female ) reporting an asthma diagnosis , symptoms of moderate to severe persistent asthma , and asthma medication use in the last 12 months were r and omized to ASMA , an 8-week school-based intervention , or a wait-list control group . They were followed for 12 months . MEASUREMENTS AND MAIN RESULTS Students completed bimonthly assessment s. Baseline , 6-month , and 12-month assessment s were comprehensive ; the others assessed interim health outcomes and urgent health care use . Primary outcomes were asthma self-management , symptom frequency , and quality of life ( QOL ) ; secondary outcomes were asthma medical management , school absences , days with activity limitations , and urgent health care use . Relative to control subjects , ASMA students reported significantly : more confidence to manage their asthma ; taking more steps to prevent symptoms ; greater use of controller medication and written treatment plans ; fewer night awakenings , days with activity limitation , and school absences due to asthma ; improved QOL ; and fewer acute care visits , emergency department visits , and hospitalizations . In contrast , steps to manage asthma episodes , daytime symptom frequency , and school-reported absences did not differentiate the two groups . Most results were sustained over the 12 months . CONCLUSIONS ASMA is efficacious in improving asthma self-management and reducing asthma morbidity and urgent health care use in low-income urban minority adolescents School-based asthma interventions delivered by nonschool staff have been successful but are limited in their reach because of the cost and effort of bringing in outside educators and their inability to establish improved communication about asthma between schools , families , and primary care providers ( PCPs ) . To address these problems , Columbia University and the New York City Department of Education and the New York City Department of Health and Mental Hygiene undertook a r and omized controlled trial to test the efficacy of a comprehensive school-based asthma program . In this intervention , school nurses were trained to facilitate the establishment of a preventive network of care for children with asthma by coordinating communications and fostering relationships between families , PCPs , and school personnel . PCPs also received training regarding asthma management . There was limited support for this model . While case detection helped nurses identify additional students with asthma and nurses increased the amount of time spent on asthma-related tasks , PCPs did not change their medical management of asthma . Few improvements in health outcomes were achieved . Relative to controls , 12-months posttest intervention students had a reduction in activity limitations due to asthma ( -35 % vs -9 % , p < .05 ) and days with symptoms ( 26 % vs 39 % , p = .06 ) . The intervention had no impact on the use of urgent health care services , school attendance , or caregiver 's quality of life . There were also no improvements at 24-months postintervention . We faced many challenges related to case detection , training , and implementing preventive care activities , which may have hindered our success . We present these challenges , describe how we coped with them , and discuss the lessons we learned BACKGROUND Childhood asthma is a serious and common chronic disease that requires the attention of nurses and other school personnel . Schools are often the first setting that children take the lead in managing their asthma . Often , children are ill prepared for this role . Our study evaluated a school-based , multifaceted asthma program that targeted students with asthma and the broader school community . METHODS A r and omized trial involving 130 schools with grade s 1 - 5 and 1316 children with asthma and their families was conducted . Outcomes of interest for the child , at 1 year , were urgent care use and school absenteeism for asthma , inhaler technique , and quality of life , and for the school , at 14 months , were indicators of a supportive school environment . RESULTS Improvements were observed at the child and school level for the intervention group . Fewer children in the intervention group had a school absence ( 50 % vs 60 % ; p < .01 ) , required urgent care for asthma ( 41 % vs 51 % ; p < .0001 ) , or reported a day of interrupted activity ( 51 % vs 63 % ; p < .01 ) , and had improved quality of life ( 5.8 ± 1.2 vs 5.4 ± 1.4 ; p < .0001 ) . Schools in the intervention group were more likely to have practice s supporting an asthma-friendly environment . CONCLUSIONS Implementation of a multifaceted school-based asthma program can lead to asthma-friendly schools that support children with asthma to be successful managers of their asthma and experience improved quality of life and decreased disease associated burden Objective : To examine the policy , administration , and supervision of medicine administration in primary schools within the Greater London area ( GLA ) . Design : A prospect i ve survey using postal question naires sent to 172 r and omly selected primary schools within the GLA . Participants : Head teachers of primary schools . Results : Some 65 % of head teachers replied . Less than 50 % of responding head teachers had actually read the national guidelines Supporting Pupils with Medical Needs and only 30 % of respondents were aware of other members of staff who had read the document . A total of 95 % of respondents followed a policy/procedure in caring for the medical needs of pupils . Over 80 % of respondents had staff h and ling the pupils ’ medical needs , staff h and ling access to stored medicines , and prior arrangements for staff training . However , it is worrying that a quarter of the schools did not keep a written record of medicines given to children in schools . The majority of staff with responsibility for medicine administration in schools are support staff . The most encouraging findings were that for the majority of schools with children using the EpiPen and rectal diazepam , there were trained staff to administer these medicines . Conclusions : The majority of schools had a policy in place to deal with medicine administration , although further work should be conducted to analyse the content of such policies . It is very important that training is directed at staff responsible for medicine administration and not just at teachers . Most schools were willing to administer rectal diazepam and EpiPen treatment in an emergency Objective . We previously conducted the School-Based Asthma Therapy trial to improve adherence to national asthma guidelines for urban children through directly observed administration of preventive asthma medications in school . The trial successfully improved outcomes among these children ; however , several factors limit its potential for dissemination . To enhance sustainability , we subsequently developed a new model of care using web-based guides for efficient communications and integration within school and community systems . This article describes the development of the School-Based Preventive Asthma Care Technology ( SB-PACT ) trial . Method . We developed the SB-PACT web-based system based on stakeholder feedback , and conducted a pilot r and omized trial with 100 children to establish its feasibility in facilitating preventive asthma care for high-risk children . The SB-PACT system represents a new model of care using web-based guides for asthma symptom screening , follow-up control assessment s , and electronic communications with providers . Result . We enrolled and successfully screened all children using the web-based system . Most providers used the electronic communication system without difficulty , and the majority of children in the intervention group received preventive medications through school as planned and dose adjustments as needed . Several challenges to implementation also were encountered . Conclusions . This program is design ed to promote sustainability of school-based asthma care , reduce program costs , and ultimately succeed in a real-world setting . With further refinements , it has the potential to be implemented nationally in schools PURPOSE The purpose was to evaluate the effectiveness of Staying Healthy-Asthma Responsible & Prepared , an academic asthma health education and counseling program , on fostering the use of effective asthma self-care behaviors . DESIGN AND METHODS This was a phase III , two-group , cluster r and omized , single-blinded , longitudinal design -guided study . Caregivers of 205 fourth- and fifth- grade students completed the asthma health behaviors survey at preintervention , and 1 , 12 , and 24 months postintervention . Analysis involved multilevel modeling . RESULTS All students demonstrated improvement in episode management , risk reduction/prevention , and health promotion behaviors ; Staying Healthy-Asthma Responsible & Prepared students demonstrated increased improvement in episode management and risk reduction/prevention behaviors . PRACTICE IMPLICATION S Working with schoolteachers , nurses can improve the use of effective asthma self-care behaviors Asthma morbidity and mortality is higher among older school-age children and early adolescents than other age groups across the lifespan . NIH recommended exp and ing asthma education to schools and community setting s to meet cognitive outcomes that have an impact on morbidity and mortality . Guided by the acceptance of asthma model , an evidence -guided , comprehensive school-based academic health education and counseling program , Staying Healthy-Asthma Responsible & Prepared ™ ( SHARP ) , was developed . The program complements existing school curricula by integrating biology , psychology , and sociology content with related spelling , math , and reading and writing assignments . Feasibility , benefits , and efficacy have been established . We compared the effectiveness of SHARP to a non-academic program , Open Airways for Schools , in improving asthma knowledge and reasoning about symptom management . A two-group , cluster-r and omized , single-blinded design was used with a sample of 205 students in grade s 4 - 5 with asthma and their caregivers . Schools were matched prior to r and omization . The unit of analysis was the student . Certified elementary school teachers delivered the programs during instructional time . Data were collected from student/caregiver dyads at baseline and at 1 , 12 , and 24 months after the intervention . In multilevel modeling , students enrolled in the academic SHARP program demonstrated significant ( p < .001 ) improvement in asthma knowledge and reasoning over students enrolled in the non-academic program . Knowledge advantages were retained at 24 months . Findings support delivery in schools of the SHARP academic health education program for students with asthma |
1,617 | 31,803,759 | Accelerated coronary calcification and plaque deposition was identified , with greater rates of increased calcium scores and sub clinical coronary artery disease shown by CTCA in women with a history of pre-eclampsia at 30 years postpartum .
The evidence was less conclusive for the persistence of long-term endothelial dysfunction . | Hypertensive disorders of pregnancy , such as pre-eclampsia , are known to be independently associated with the development of premature cardiovascular disease ( CVD ) in women .
In pre-eclampsia , the placenta secretes excess anti-angiogenic factors into the maternal circulation , leading to widespread endothelial damage , and inflammation .
This endothelial damage is evidence d to persist beyond the acute illness .
However , whether it is permanent and responsible for the elevated rates of premature CVD seen in this at-risk group remains unclear . | Abstract Background Systemic endothelial dysfunction has been identified as one of the main events in preeclampsia ( PE ) . A nonhealthy vascular endothelium can be pointed out as the pathophysiological explanation of the clinical manifestations and complications of PE . Once normal pregnancy is characterized by a constant increase in endothelial function , a follow-up of this physiological event could be used as an early marker or a prediction tool to predict PE . Objectives To perform a longitudinal assessment of endothelial function , using an ultrasound study of brachial artery flow Flow-mediated dilation ( FMD ) , in normotensive and preeclamptic pregnancies , to evaluate the difference of FMD values along the second trimester of pregnancy to predict PE . Patients and methods In a prospect i ve cohort study , 91 pregnant women with a high risk of developing PE were subjected to FMD of the brachial artery . The difference in the FMD values , between 16 + 0 and 19 + 6 and 24 + 0 and 27 + 6 weeks of gestation were compared , taking PE development into consideration . Receiver operator characteristics ( ROC ) curves were created to determine the sensibility and specificity of FMD difference to predict PE . Results A total of 19 patients developed PE and the other 72 women remained normotensive until 1 week after delivery . When considering a cut off of + 2.50 % , FMD difference , between the two evaluations , sensitivity for PE prediction was 87.5 % for early onset PE and 95.5 % for late PE . Conclusion The difference of FMD values between the second trimester of pregnancy can be used for PE prediction for both , early and late forms of PE Background Preterm preeclampsia is an important cause of maternal and perinatal death and complications . It is uncertain whether the intake of low‐dose aspirin during pregnancy reduces the risk of preterm preeclampsia . Methods In this multicenter , double‐blind , placebo‐controlled trial , we r and omly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin , at a dose of 150 mg per day , or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation . The primary outcome was delivery with preeclampsia before 37 weeks of gestation . The analysis was performed according to the intention‐to‐treat principle . Results A total of 152 women withdrew consent during the trial , and 4 were lost to follow up , which left 798 participants in the aspirin group and 822 in the placebo group . Preterm preeclampsia occurred in 13 participants ( 1.6 % ) in the aspirin group , as compared with 35 ( 4.3 % ) in the placebo group ( odds ratio in the aspirin group , 0.38 ; 95 % confidence interval , 0.20 to 0.74 ; P=0.004 ) . Results were material ly unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow‐up . Adherence was good , with a reported intake of 85 % or more of the required number of tablets in 79.9 % of the participants . There were no significant between‐group differences in the incidence of neonatal adverse outcomes or other adverse events . Conclusions Treatment with low‐dose aspirin in women at high risk for preterm preeclampsia result ed in a lower incidence of this diagnosis than placebo . ( Funded by the European Union Seventh Framework Program and the Fetal Medicine Foundation ; EudraCT number , 2013‐003778‐29 ; Current Controlled Trials number , IS RCT N13633058 . This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS Boston University Patricia Cortes Harvard University Claudia Goldin Swarthmore College Jennifer Background — Preeclampsia is a life-threatening pregnancy syndrome of uncertain origin . To eluci date the pathogenesis , we evaluated the temporal relationships between changes in vascular function and circulating biomarkers of angiogenic activity before and after the onset of preeclampsia and gestational hypertension . Methods and Results — Maternal mean arterial pressure , uterine artery pulsatility index , brachial artery flow-mediated dilatation , and serum concentrations of placental growth factor ( PlGF ) , soluble fms-like tyrosine kinase 1 ( sFlt-1 ) , and soluble endoglin were prospect ively measured in 159 women from 10 weeks gestation until 12 weeks postpartum . At 10 to 17 weeks , women who developed preterm preeclampsia had lower serum PlGF ( P=0.003 ) , higher soluble endoglin ( P=0.006 ) , and higher sFlt-1:PlGF ratio ( P=0.005 ) compared with women who later developed term preeclampsia , gestational hypertension , or normotensive pregnancy . At 10 to 17 weeks , mean arterial pressure inversely correlated with serum PlGF ( r=−0.19 , P=0.02 ) ; at 18 to 25 weeks , with soluble endoglin ( r=0.18 , P=0.02 ) ; and at 26 to 33 weeks , with sFlt-1 ( r=0.28 , P<0.001 ) . At 23 to 25 weeks , uterine artery pulsatility index correlated with serum soluble endoglin ( r=0.19 , P=0.02 ) and sFlt-1 levels ( r=0.17 , P=0.03 ) . Flow-mediated dilatation was higher during a pregnancy with gestational hypertension compared with preeclampsia ( P=0.001 ) . Twelve weeks postpartum , serum PlGF was higher in women who had a hypertensive pregnancy compared with a normotensive pregnancy ( P<0.001 ) . Conclusions — These observations support a role for placenta-derived angiogenic biomarkers in the control of maternal vascular resistance of preeclampsia . Gestational hypertension develops differently , with a hyperdynamic circulation and angiogenic biomarker profile similar to normotensive pregnancy . Larger studies of unselected women are needed to ascertain whether measures of these angiogenic biomarkers assist with the prediction and prognosis of preeclampsia and whether postpartum measures of serum PlGF have a role in predicting future cardiovascular disease Background — Coronary artery calcium ( CAC ) has been demonstrated to be associated with the risk of coronary heart disease . The Multi-Ethnic Study of Atherosclerosis ( MESA ) provides a unique opportunity to examine the distribution of CAC on the basis of age , gender , and race/ethnicity in a cohort free of clinical cardiovascular disease and treated diabetes . Methods and Results — MESA is a prospect i ve cohort study design ed to investigate sub clinical cardiovascular disease in a multiethnic cohort free of clinical cardiovascular disease . The percentiles of the CAC distribution were estimated with nonparametric techniques . Treated diabetics were excluded from analysis . There were 6110 included in the analysis , with 53 % female and an average age of 62 years . Men had greater calcium levels than women , and calcium amount and prevalence were steadily higher with increasing age . There were significant differences in calcium by race , and these associations differed across age and gender . For women , whites had the highest percentiles and Hispanics generally had the lowest ; in the oldest age group , however , Chinese women had the lowest values . Overall , Chinese and black women were intermediate , with their order dependent on age . For men , whites consistently had the highest percentiles , and Hispanics had the second highest . Blacks were lowest at the younger ages , and Chinese were lowest at the older ages . At the MESA public website ( http://www.mesa-nhlbi.org ) , an interactive form allows one to enter an age , gender , race/ethnicity , and CAC score to obtain a corresponding estimated percentile . Conclusions — The information provided here can be used to examine whether a patient has a high CAC score relative to others with the same age , gender , and race/ethnicity who do not have clinical cardiovascular disease or treated diabetes Preeclampsia is a leading cause of maternal morbidity and mortality . The degree of maternal cardiovascular dysfunction that precedes the onset of preeclampsia is largely unknown . This prospect i ve cohort study aim ed to characterize differences in vivo in retinal microvascular caliber and blood pressure throughout pregnancy in relation to preeclampsia development . Women were recruited from Royal Prince Alfred Hospital , Sydney , Australia , of which 92 women were included in the study . Retinal images and blood pressures were collected at 13 , 19 , 29 , and 38 weeks of gestation . Retinal vessels were analyzed as the central retinal arteriolar equivalent corrected for mean arterial blood pressure and the central retinal venular equivalent corrected for mean arterial blood pressure , using generalized linear models adjusted for age and body mass index . The preeclampsia group were significantly older ( P=0.002 ) and had a significantly higher mean body mass index ( P=0.005 ) . The central retinal arteriolar equivalent corrected for mean arterial blood pressure was significantly reduced at 13 ( P=0.03 ) , 19 ( P=0.007 ) , and 38 ( P=0.03 ) weeks of gestation in the preeclampsia group . The central retinal venular equivalent corrected for mean arterial blood pressure was also significantly lower at 13 ( P=0.04 ) and 19 ( P=0.001 ) weeks of gestation in the women who progressed to preeclampsia . This study directly documents increased peripheral resistance in vivo , observed as the combination of constricted retinal arterioles or venules and elevated blood pressure , in women who later developed preeclampsia . This difference preceded the clinical signs of preeclampsia OBJECTIVES The purpose of this study was to determine the prognostic accuracy of electron beam computed tomographic ( CT ) scanning of the coronary arteries and the relationship of coronary calcification to st and ard coronary disease risk factors and C-reactive protein ( CRP ) in the prediction of atherosclerotic cardiovascular disease ( ASCVD ) events in apparently healthy middle-age persons . BACKGROUND As a screening test for coronary artery disease ( CAD ) , electron beam CT scanning remains controversial . METHODS In a prospect i ve , population -based study , 4,903 asymptomatic persons age 50 to 70 years underwent electron beam CT scanning of the coronary arteries . RESULTS At 4.3 years , follow-up was available in 4,613 participants ( 94 % ) , and 119 had sustained at least one ASCVD event . Subjects with ASCVD events had higher baseline coronary calcium scores ( median [ interquartile range ] , Agatston method ) than those without events : 384 ( 127 , 800 ) versus 10 ( 0 , 86 ) ( p < 0.0001 ) . For coronary calcium score threshold > or = 100 versus < 100 , relative risk ( 95 % confidence interval ) was 9.6 ( 6.7 to 13.9 ) for all ASCVD events , 11.1 ( 7.3 to 16.7 ) for all CAD events , and 9.2 ( 4.9 to 17.3 ) for non-fatal myocardial infa rct ion and death . The coronary calcium score predicted CAD events independently of st and ard risk factors and CRP ( p = 0.004 ) , was superior to the Framingham risk index in the prediction of events ( area under the receiver-operating characteristic curve of 0.79 + /- 0.03 vs. 0.69 + /- 0.03 , p = 0.0006 ) , and enhanced stratification of those falling into the Framingham categories of low , intermediate , and high risk ( p < 0.0001 ) . CONCLUSIONS The electron beam CT coronary calcium score predicts CAD events independent of st and ard risk factors , more accurately than st and ard risk factors and CRP , and refines Framingham risk stratification OBJECTIVES To assess the evolution of the soluble fms-like tyrosine kinase-1 ( sFlt-1 ) to placental growth factor ( PlGF ) ratio in women with suspected or confirmed pre-eclampsia ( PE ) , and to investigate the changes in sFlt-1 and PlGF levels in pre-eclamptic women after delivery . METHODS This was an exploratory study in which secondary analysis was performed on a prospect i ve cohort study that enrolled women with a singleton pregnancy and suspected or confirmed PE from 18 weeks ' gestation , carried out between December 2013 and April 2016 at the Department of Obstetrics of the Erasmus Medical Center in Rotterdam . sFlt-1 and PlGF were determined using Roche Diagnostics Elecsys assays in two groups of patients . In the first group , patients with suspected or confirmed PE had sFlt-1 and PlGF levels measured at least twice during their pregnancy . Changes in these biomarkers over the course of pregnancy were compared for patients in this group with a baseline sFlt-1/PlGF ratio of ≤ 38 and for those with a ratio > 38 . In the second group , sFlt-1 and PlGF levels of women with PE or HELLP syndrome were measured before and after delivery . For this group , pre- and postpartum sFlt-1 and PlGF levels were compared and half-lives were calculated . RESULTS Women with suspected or confirmed PE for whom sFlt-1 and PlGF levels were measured at least twice during pregnancy ( n = 46 ) had a median gestational age at inclusion of 26 weeks ( range , 18 - 40 weeks ) . In 27 of the 30 patients with sFlt-1/PlGF ratio ≤ 38 at baseline , thereby ruling out PE , the sFlt-1/PlGF ratio remained stable for up to 100 days . In the remaining three patients with a ratio ≤ 38 and in most of the 16 patients with a ratio > 38 , the ratio increased further . For women diagnosed with PE or HELLP syndrome for whom sFlt-1 and PlGF levels were measured before and after delivery ( n = 26 ) , median gestational age at inclusion was 29 weeks ( range , 16 - 37 weeks ) and median time between antepartum measurement and delivery was 2 days ( range , 1 - 17 days ) . In this group , after delivery , sFlt-1 dropped to < 1 % of its pre-delivery value , with a half-life of 1.4 ± 0.3 days , while PlGF dropped to ∼30 % of its pre-delivery value , with a half-life of 3.7 ± 4.3 days . CONCLUSIONS Based on this small cohort , up to 10 % of pregnant women admitted with suspected or confirmed PE presenting with a sFlt-1/PlGF ratio of ≤ 38 display a rise in sFlt-1/PlGF ratio in subsequent weeks , implying that repeat determination of the sFlt-1/PlGF ratio is required to exclude definitively a diagnosis of PE . Furthermore , the rapid and pronounced decline in sFlt-1 levels after delivery in patients with PE/HELLP syndrome suggests that sFlt-1 , in contrast to PlGF , is almost entirely derived from the placenta . Copyright © 2017 ISUOG . Published by John Wiley & Sons OBJECTIVE Soluble vascular endothelial growth factor receptor 1 ( sVEGFR-1 ) , which antagonizes VEGF functions , has been implicated in the pathophysiology of preeclampsia . The purpose of this study was to determine whether preeclampsia is associated with a change in the plasma concentration of sVEGFR-1 , and , if so , whether such a change is correlated with the severity of the disease . METHODS A cross-sectional study was conducted to determine the concentrations of sVEGFR-1 in plasma obtained from normal pregnant women ( n=61 ) and patients with preeclampsia ( n=61 ) . Plasma concentrations of sVEGFR-1 were determined by enzyme-linked immunoassay . RESULTS Preeclampsia had a higher median plasma concentration of sVEGFR-1 than normal pregnancy ( P < .001 ) . The median plasma concentration of sVEGFR-1 was higher in early-onset ( < or = 34 weeks ) than late-onset ( > 34 weeks ) preeclampsia ( P=.005 ) , and higher in severe than in mild preeclampsia ( P=.002 ) . In normal pregnancy , there was a correlation between plasma concentration of sVEGFR-1 and gestational age ( r=0.5 ; P < .001 ) . In contrast , there was a negative correlation between plasma concentration of sVEGFR-1 and gestational age at the onset of preeclampsia ( r=-0.5 ; P < .001 ) . CONCLUSION Preeclampsia is associated with an increased plasma sVEGFR-1 concentration . The elevation of sVEGFR-1 concentration is correlated with the severity of the disease . These observations suggest the participation of VEGF and its soluble receptor in the pathophysiology of preeclampsia OBJECTIVE Women who have had preeclampsia demonstrate higher prevalence of metabolic syndrome ( MetS ) , impaired vascular function , and increased sympathetic activity and are at increased risk of cardiovascular disease . The aim of this study was to assess the effects of 12 weeks of exercise training ( 70 - 80 % maximum volume of oxygen utilization ) in women who had had preeclampsia on physical fitness , components of MetS , vasculature , and autonomic functions compared with healthy control subjects . STUDY DESIGN Our prospect i ve case-control study included 24 normotensive women who had had preeclampsia and 20 control subjects who were matched for age and postpartum interval ( all 6 - 12 months after delivery ) . Before and after training , we measured all components of MetS ( ie , BP , lipids , glucose/insulin , and albuminuria ) , carotid intima media thickness ( IMT ) and brachial and superficial femoral artery endothelial function that used flow-mediated dilation ( FMD ) . Autonomic activity was quantified with power spectral analysis ( low-frequency/high-frequency power [ LF/HF ] ratio ) . RESULTS At baseline , women who had had preeclampsia demonstrated higher values of most components of MetS. Compared with the control subjects , women who had had preeclampsia had increased IMT ( 580 ± 92 μm vs 477 ± 65 μm , respectively ) , impaired endothelial function ( FMD brachial artery , 5.3 % ± 2.2 % vs 10.8 % ± 3.5 % , respectively ; FMD superficial femoral artery , 4.9 % ± 2.1 % vs 8.7 % ± 3.2 % , respectively ) and increased LF/HF power ratio ( 2.2 ± 1.0 vs 1.3 ± 0.4 , respectively ; all P < .05 ) . In both groups , exercise training decreased values of most components of MetS and IMT , improved FMD , and concurrently reduced LF/HF . Despite these improvements , vascular and autonomic variables did not normalize by 12 weeks of training in women who had had preeclampsia . CONCLUSION This study demonstrates that exercise training in women who had had preeclampsia and control subjects improves components of MetS , endothelial function , vascular wall thickness , and autonomic control . Nonetheless , trained women who had had preeclampsia only reached a cardiovascular status that is comparable with sedentary healthy control subjects Objectives : To determine whether brachial artery flow-mediated dilation ( FMD ) assessed by ultrasonography during the late first trimester is able to predict the occurrence of hypertensive disorders during pregnancy . Methods : Maternal endothelial function was assessed by flow-mediated dilation ( FMD ) of the brachial artery in 487 pregnant women at 11 - 13 + 6 weeks ' gestation . Subjects were prospect ively followed and grouped according to the outcomes related to hypertensive disorders . We determined the areas under receiver operating characteristic ( ROC ) curve with their respective 95 % confidence intervals ( CI ) for using low FMD results to predict the occurrence of hypertensive disorders during pregnancy . Results : Among 487 women , 9 ( 1.8 % ) were diagnosed with early-onset preeclampsia , 22 ( 4.5 % ) were diagnosed with late-onset preeclampsia , 47 ( 9.7 % ) developed gestational hypertension , and the remaining 409 ( 84 % ) pregnancies were unaffected by hypertensive disorders . Area under ROC curve analyses demonstrated that FMD was not able to predict pregnancies that developed hypertensive disorders . Conclusions : We conclude that FMD should not be considered a potential first-trimester marker of hypertensive disorders during pregnancy AIM Aim of the present study was to evaluate the association between endothelial dysfunction , evaluated through flow-mediated dilation ( FMD ) of the brachial artery , and preeclampsia . METHODS A case-control prospect i ve cross-sectional study was conducted on 81 pregnant women of between 20 and 39 weeks and 5 days , among whom 40 had preeclampsia and 41 were controls . The right brachial artery was identified using color Doppler , between 2 and 5 cm above the cubital fold . The diameter of the brachial artery was measured by calculating the distance between the proximal and distal intima ( D1 ) during diastoles . Ischemia was caused for five minutes and the artery measurement was repeated 60 seconds after ending the compression ( D2 ) , during diastoles . The FMD ( % ) was calculated through the equation : (D2-D1)/D1 × 100 . The association between independent variables and the presence of preeclampsia was estimated through odds ratios ( OR ) and their 95 % confidence intervals ( 95 % CI ) . RESULTS Seventy-five percent of the pregnant women with preeclampsia and 26.8 % of the normotensive women presented reduction in the diameter of the brachial artery ( OR = 8.18 ; 95 % CI : 2.74 - 25.04 ) ( P = 0.000 ) . A greater proportion of the pregnant women with pre-eclampsia ( 42.1 % vs. 14.3 % ) had a history of a mother with hypertension during pregnancy ( OR = 4.36 ; 95 % CI : 0.89 - 23.51 ) ( P = 0.045 ) . CONCLUSION We identified an association between endothelial dysfunction , evaluated through FMD of the brachial artery , and preeclampsia BACKGROUND A history of preeclampsia is an independent risk factor for cardiac events and stroke . Changes in vasculature structure that contribute to these associations are not well understood . OBJECTIVE The aim of this study was to quantify coronary artery calcification ( CAC ) , a known risk factor for cardiac events , in a prospect i ve cohort of women with and without histories of preeclampsia . STUDY DESIGN Women without prior cardiovascular events ( 40 with and 40 without histories of preeclampsia , matched for parity and age at index birth ) were recruited from a large population -based cohort of women who were residents of Olmsted County , Minnesota , and who delivered from 1976 through 1982 . Computed tomography was performed to measure CAC in Agatston units . All pregnancy histories and covariates were confirmed by review of the medical records . Current clinical variables were assessed at the time of imaging . Differences between women with and without histories of preeclampsia were examined using χ(2 ) tests and tests ; CAC , in particular , was compared as a categorical and ordinal variable , with a χ(2 ) test and with Wilcoxon 2- sample tests and ordinal logistic regression , as appropriate . RESULTS Mean age ( SD ) at imaging was 59.5 ( ±4.6 ) years . Systolic and diastolic blood pressures , hyperlipidemia , and current diabetes status did not differ between women with and without histories of preeclampsia . However , the frequencies of having a current clinical diagnosis of hypertension ( 60 % vs 20 % , P < .001 ) and higher body mass index in kg/m(2 ) ( expressed as median [ 25th-75th percentile ] , 29.8 [ 25.9 - 33.7 ] vs 25.3 [ 23.1 - 32.0 ] , P = .023 ) were both greater in the women with histories of preeclampsia compared to those without . The frequency of a CAC score > 50 Agatston units was also greater in the preeclampsia group ( 23 % vs 0 % , P = .001 ) . Compared to women without preeclampsia , the odds of having a higher CAC score was 3.54 ( confidence interval [ CI ] , 1.39 - 9.02 ) times greater in women with prior preeclampsia without adjustment , and 2.61 ( CI , 0.95 - 7.14 ) times greater after adjustment for current hypertension . After adjustment for body mass index alone , the odds of having a higher CAC based on a history of preeclampsia remained significant at 3.20 ( CI , 1.21 - 8.49 ) . CONCLUSION In this first prospect i ve cohort study with confirmation of preeclampsia by medical record review , a history of preeclampsia is associated with an increased risk of CAC > 30 years after affected pregnancies , even after controlling individually for traditional risk factors . A history of preeclampsia should be considered in risk assessment when initiating primary prevention strategies to reduce cardiovascular disease in women . Among women with histories of preeclampsia , the presence of CAC may be able to identify those at a particularly high cardiovascular risk , and should be the subject of future studies |
1,618 | 32,125,669 | Firstly , previous experience/habituation has been suggested as a factor that provides learning and information about the treatment [ 11 ] , thereby driving participants ’ expectations about caffeine ’s ergogenic effects . | While insightful , their review paid little attention to an aspect that has been frequently omitted in sports nutrition fields : the effects of the expectation of receiving caffeine on exercise performance .
In addition to the caffeine-induced pharmacological responses , the expectation of ingesting caffeine may also trigger a powerful ergogenic response known as “ placebo effect ” [ 2 , 3 ] .
From an exercise performance perspective , placebo has been defined as an inert substance or procedure of a given treatment/intervention [ 4 ] that enhances performance outcomes [ 5 ] .
Despite their mechanisms being minimally understood , placebo effects have been attributed to endogenous opioids and subthalamic nucleus neuron activation [ 6 ] , decreased pain transmission [ 7 ] , and released dopamine in the dorsal and ventral striatum [ 8 , 9 ] .
In this regard , one of the most powerful triggers of placebo effects in caffeineexercise performance studies is the expectation of receiving caffeine , as caffeine is known as a potential , beneficial ergogenic aid .
Secondly , either the prior knowledge of the treatment or the intention to use a sports ergogenic aid may potentiate individuals ’ responses to placebo ingestion [ 9 , 12 ] .
Thirdly , personality traits may also affect placebo effects , as optimism can increase the perception of the positive effects of a given treatment ; in contrast , pessimism , fear , and anxiety have been associated with nocebo responses through an increased negative effects perception of treatment .
Most caffeine-exercise studies have followed general recommendations for well-controlled trials in clinical setting s [ 14 , 15 ] , so that a double-blind placebo design [ 14 , 15 ] having only a placebo group/condition as a control ( that is , single control condition ) has been traditionally used when investigating pharmacological caffeine effects .
However , a single control with placebo has been criticized [ 2 , 3 , 16 ] as the belief in ingesting an active substance such as caffeine may change the participants ’ motivation and self-efficacy , leading to some beneficial effect on performance responses [ 9 ] . | Caffeine , an adenosine receptor antagonist , has shown to improve performance in normal ambient temperature , presumably via an effect on dopaminergic neurotransmission through the antagonism of adenosine receptors . However , there is very limited evidence from studies that administered caffeine and examined its effects on exercise in the heat . Therefore , we wanted to study the effects of caffeine on performance and thermoregulation in high ambient temperature . Eight healthy trained male cyclists completed two experimental trials ( in 30 ° C ) in a double-blind-r and omized crossover design . Subjects ingested either placebo ( 6 mg/kg ) or caffeine ( 6 mg/kg ) 1 h prior to exercise . Subjects cycled for 60 min at 55 % Wmax , immediately followed by a time trial to measure performance . The significance level was set at p < 0.05 . Caffeine did not change performance ( p = 0.462 ) . Rectal temperature was significantly elevated after caffeine administration ( p < 0.036 ) . Caffeine significantly increased B-endorphin plasma concentrations at the end of the time trial ( p = 0.032 ) . The present study showed no ergogenic effect of caffeine when administered 1 h before exercise in 30 ° C . This confirms results from a previous study that examined the effects of caffeine administration on a short ( 15 min ) time trial in 40 ° C . However , caffeine increased core temperature during exercise . Presumably , the rate of increase in core temperature may have counteracted the ergogenic effects of caffeine . However , other factors such as interindividual differences in response to caffeine and changes in neurotransmitter concentrations might also be responsible for the lack of performance improvement of caffeine in high ambient temperature This study compared the effects of a single and divided dose of caffeine on endurance performance and on postexercise urinary caffeine and plasma paraxanthine concentrations . Nine male cyclists and triathletes cycled for 90 min at 68 % of maximal oxygen uptake , followed by a self-paced time trial ( work equivalent to 80 % of maximal oxygen uptake workload over 30 min ) with three r and omized , balanced , and double-blind interventions : 1 ) placebo 60 min before and 45 min into exercise ( PP ) ; 2 ) single caffeine dose ( 6 mg/kg ) 60 min before exercise and placebo 45 min into exercise ( CP ) ; and 3 ) divided caffeine dose ( 3 mg/kg ) 60 min before and 45 min into exercise ( CC ) . Time trial performance was unchanged with caffeine ingestion ( P = 0.08 ) , but it tended to be faster in the caffeine trials ( CP : 24.2 min and CC : 23.4 min ) compared with placebo ( PP : 28.3 min ) . Postexercise urinary caffeine concentration was significantly lower in CC ( 3.8 micro g/ml ) compared with CP ( 6.8 micro g/ml ) . Plasma paraxanthine increased in a dose-dependent fashion and did not peak during exercise . In conclusion , dividing a caffeine dose provides no ergogenic effect over a bolus dose but reduces postexercise urinary concentration The power of placebos has long been recognized for improving numerous medical conditions such as Parkinson 's disease ( PD ) . Little is known , however , about the mechanism underlying the placebo effect . Using the ability of endogenous dopamine to compete for [11C]raclopride binding as measured by positron emission tomography , we provide in vivo evidence for substantial release of endogenous dopamine in the striatum of PD patients in response to placebo . Our findings indicate that the placebo effect in PD is powerful and is mediated through activation of the damaged nigrostriatal dopamine system Purpose Many studies have examined the effect of caffeine on exercise performance , but findings have not always been consistent . The objective of this study was to determine whether variation in the CYP1A2 gene , which affects caffeine metabolism , modifies the ergogenic effects of caffeine in a 10-km cycling time trial . Methods Competitive male athletes ( n = 101 ; age = 25 ± 4 yr ) completed the time trial under three conditions : 0 , 2 , or 4 mg of caffeine per kilogram body mass , using a split-plot r and omized , double-blinded , placebo-controlled design . DNA was isolated from saliva and genotyped for the −163A > C polymorphism in the CYP1A2 gene ( rs762551 ) . Results Overall , 4 mg·kg−1 caffeine decreased cycling time by 3 % ( mean ± SEM ) versus placebo ( 17.6 ± 0.1 vs 18.1 ± 0.1 min , P = 0.01 ) . However , a significant ( P < 0.0001 ) caffeine – gene interaction was observed . Among those with the AA genotype , cycling time decreased by 4.8 % at 2 mg·kg−1 ( 17.0 ± 0.3 vs 17.8 ± 0.4 min , P = 0.0005 ) and by 6.8 % at 4 mg·kg−1 ( 16.6 ± 0.3 vs 17.8 ± 0.4 min , P < 0.0001 ) . In those with the CC genotype , 4 mg·kg−1 increased cycling time by 13.7 % versus placebo ( 20.8 ± 0.8 vs 18.3 ± 0.5 min , P = 0.04 ) . No effects were observed among those with the AC genotype . Conclusion Our findings show that both 2 and 4 mg·kg−1 caffeine improve 10-km cycling time , but only in those with the AA genotype . Caffeine had no effect in those with the AC genotype and diminished performance at 4 mg·kg−1 in those with the CC genotype . CYP1A2 genotype should be considered when deciding whether an athlete should use caffeine for enhancing endurance performance Aim The purpose of this study was to examine the effect of CYP1A2 -163C > A polymorphism on the ergogenic effects of caffeine supplementation during a resistance exercise ( RE ) session . Methods In a r and omized , double-blind , placebo (PL)-controlled , crossover study , 30 resistance-trained men took part in two RE sessions ( three sets to failure at 85 % of one repetition maximum , 2-min rest between sets ) , including bench press ( BP ) , leg press ( LP ) , seated cable row , and shoulder press ( SP ) following caffeine ( CAF ) ( 6 mg kg−1 ) or PL ( 6 mg kg−1 of maltodextrin ) ingestion 1 h prior to the trial . The number of repetitions was recorded after each set , along with calculation of total number of repetitions for each exercise . Genomic DNA was isolated from the whole blood sample s for analyzing the CYP1A2 -163C > A polymorphism through amplification refractory mutation system – polymerase chain reaction ( ARMS – PCR ) . Subjects were classified as either AA ( n = 14 ) or AC/CC genotypes ( n = 16 ) . Results The two-way ANOVA with repeated measures revealed differences between AAs and AC/CCs under CAF conditions for repetitions performed in sets 1 , 2 , and 3 of BP ( F(1 , 28 ) = 14.84 , P = 0.001 , ƞ2 = 0.34 ) , LP ( F(1 , 28 ) = 8.92 , P = 0.006 , ƞ2 = 0.24 ) , SR ( F(1 , 28 ) = 17.38 , P = 0.0001 , ƞ2 = 0.38 ) , and SP ( F(1 , 28 ) = 3.76 , P = 0.063 , ƞ2 = 0.11 ) . CAF also increased the total number of repetitions performed for all three sets in AAs versus AC/CCs for BP ( F(1 , 28 ) = 8.72 , P = 0.006 , ƞ2 = 0.23 ) , LP ( F(1 , 28 ) = 4.67 , P = 0.03 , ƞ2 = 0.14 ) , SR ( F(1 , 28 ) = 5.54 , P = 0.02 , ƞ2 = 0.16 ) , and SP ( F(1 , 28 ) = 3.89 , P = 0.058 , ƞ2 = 0.12 ) in athletes who were homozygous carriers of the A allele , compared to the C allele carriers . Therefore , AA homozygotes were able to carry out a greater total volume of RE work under CAF but not PL conditions , compared to the C allele carriers . Conclusion In conclusion , acute ingestion of CAF significantly enhanced RE performance in resistance-trained men who were homozygous for the A allele , but not for C allele carriers . Further studies are needed to replicate the potential role of the CYP1A2 -163C > A polymorphism on the ergogenic effects of CAF in other modes of exercise and in other population PURPOSE To determine the effects of ingesting caffeine ( CAFF ) and sodium bicarbonate ( SB ) , taken individually and simultaneously , on 3-km cycling time-trial ( TT ) performance . METHOD Ten well-trained cyclists , age 24.2 ± 5.4 yr , participated in this acute-treatment , double-blind , crossover study that involved four 3-km cycling TTs performed on separate days . Before each TT , participants ingested either 3 mg/kg body mass ( BM ) of CAFF , 0.3 g · kg⁻¹ · BM⁻¹ of SB , a combination of the two ( CAFF+SB ) , or a placebo ( PLAC ) . They completed each 3-km TT on a laboratory-based cycle ergometer , during which physiological , perceptual , and performance measurements were determined . For statistical analysis , the minimal worthwhile difference was considered ~1 % based on previous research . RESULTS Pretrial pH and HCO₃ were higher in SB and CAFF+SB than in the CAFF and PLAC trials . Differences across treatments for perceived exertion and gastric discomfort were mostly unclear . Compared with PLAC , mean power output during the 3-km TT was higher in CAFF , SB , and CAFF+SB trials ( 2.4 % , 2.6 % , 2.7 % respectively ) , result ing in faster performance times ( -0.9 , -1.2 , -1.2 % respectively ) . Effect sizes for all trials were small ( 0.21 - 0.24 ) . CONCLUSIONS When ingested individually , both CAFF and SB enhance high-intensity cycling TT performance in trained cyclists . However , the ergogenic effect of these 2 popular supplements was not additive , bringing into question the efficacy of coingesting the 2 supplements before short- duration high-intensity exercise . In this study there were no negative effects of combining CAFF and SB , 2 relatively inexpensive and safe supplements Hudson , GM , Green , JM , Bishop , PA , and Richardson , MT . Effects of caffeine and aspirin on light resistance training performance , RPE , and pain perception . J Strength Cond Res 22(6 ) : 1950 - 1957 , 2008-This study compared independent effects of caffeine and aspirin on muscular endurance ( repetitions ) , heart rate ( HR ) , perceived exertion ( RPE ) , and perceived pain index ( PPI ) during light resistance training bouts performed to volitional failure . It was hypothesized that the hypoalgesic properties of these ergogenic aids would decrease pain perception and potentially result in enhanced performance . College-aged men ( n = 15 ) participated in a within-subjects , double-blind study with three independent , counterbalanced sessions wherein aspirin ( 10 mg·kg−1 ) , caffeine ( 6 mg·kg−1 ) , or matched placebo were ingested 1 hour before exercise , and RPE , HR , PPI , and repetitions ( per set and total per exercise ) were recorded at 100 % of individual , predetermined , 12-repetition maximum for leg extensions ( LE ) and seated arm curls ( AC ) . Repeated- measures analyses of variance were used for between-trial comparisons . Caffeine result ed in significantly greater ( p < 0.05 ) HR ( LE and AC ) , total repetitions ( LE ) , and repetitions in set 1 ( LE and AC ) compared with aspirin and placebo . Aspirin result ed in significantly higher PPI in set 1 ( LE ) . In LE , 47 % of participants ' performance exceeded the predetermined effect size ( ≥ 5 repetitions ) for total repetitions , with 53 % exceeding the effect size ( ≥ 2 repetitions ) for repetitions in set 1 with caffeine ( vs. placebo ) . In AC , 53 % ( total repetitions ) and 47 % ( set 1 repetitions ) of participants exceeded effect sizes with caffeine ( vs. placebo ) , with only 13 % experiencing decrements in performance ( total repetitions ) . Aspirin also produced a higher PPI and RPE overall and in set 1 ( vs. placebo ) . This study demonstrates that caffeine significantly enhanced resistance training performance in LE and AC , whereas aspirin did not . Athletes may improve their resistance training performance by acute ingestion of caffeine . As with most ergogenic aids , our analyses indicate that individual responses vary greatly BACKGROUND The ingestion of either caffeine ( C ) or ephedrine ( E ) has been shown to improve performance during high-intensity aerobic activity lasting 10 - 20 min , with an additive effect being found when the combination ( C + E ) was ingested . It was the purpose of this study to determine if the addition of E to C would improve performance in activity lasting longer than 20 min . METHODS One and one half hours after ingesting a placebo ( P ) , C ( 4 mg/kg ) , E ( 0.8 mg/kg ) , or C + E , 12 subjects performed a 10-km run while wearing a helmet and backpack weighing 11 kg . The trials were performed in a climatic suite at 12 - 13 degrees C , on a treadmill where the speed was regulated by the subject . VO(2 ) , VCO(2 ) , V(E ) , heart rate ( HR ) , and rating of perceived exertion ( RPE ) were measured during the run at 15 and 30 min , and again when the individual reached 9 km . Blood was sample d at 15 and 30 min and again at the end of the run and assayed for lactate , glucose , and catecholamines . RESULTS Run times ( mean + /- SD ) , in minutes , were for C ( 46.0 + /- 2.8 ) , E ( 45.5 + /- 2.9 ) , C + E ( 45.7 + /- 3.3 ) , and P ( 46.8 + /- 3.2 ) . The run times for the E trials ( E and C + E ) were significantly reduced compared with the non-E trials ( C and P ) . Pace was increased for the E trials compared with the non-E trials over the last 5 km of the run . VO(2 ) was not affected by drug ingestion . HR was elevated for the ephedrine trials ( E and C + E ) . RPE remained similar for all trails . Caffeine increased the epinephrine and norepinephrine response associated with exercise and also increased blood lactate , glucose , and glycerol levels . Ephedrine reduced the epinephrine response but increased dopamine and FFA levels . CONCLUSION The previously seen additive nature of E and C was not evident in this study , with the primary ergogenic effect being attributed to The purpose of this study was to examine the acute effects of a caffeine-containing supplement on upper- and lower-body strength and muscular endurance as well as anaerobic capabilities . Thirty-seven resistance-trained men ( mean ± SD , age : 21 ± 2 years ) volunteered to participate in this study . On the first laboratory visit , the subjects performed 2 Wingate Anaerobic Tests ( WAnTs ) to determine peak power ( PP ) and mean power ( MP ) , as well as tests for 1 repetition maximum ( 1RM ) , dynamic constant external resistance strength , and muscular endurance ( TOTV ; total volume of weight lifted during an endurance test with 80 % of the 1RM ) on the bilateral leg extension ( LE ) and free-weight bench press ( BP ) exercises . Following a minimum of 48 hours of rest , the subjects returned to the laboratory for the second testing session and were r and omly assigned to 1 of 2 groups : a supplement group ( SUPP ; n = 17 ) , which ingested a caffeine-containing supplement , or a placebo group ( PLAC ; n = 20 ) , which ingested a cellulose placebo . One hour after ingesting either the caffeine-containing supplement or the placebo , the subjects performed 2 WAnTs and were tested for 1RM strength and muscular endurance on the LE and BP exercises . The results indicated that there was a significant ( p < 0.05 ) increase in BP 1RM for the SUPP group , but not for the PLAC group . The caffeine-containing supplement had no effect , however , on LE 1RM , LE TOTV , BP TOTV , PP , and MP . Thus , the caffeine-containing supplement may be an effective supplement for increasing upper-body strength and , therefore , could be useful for competitive and recreational athletes who perform resistance training Blinding embodies a rich history spanning over two centuries . Most research ers worldwide underst and blinding terminology , but confusion lurks beyond a general comprehension . Terms such as single blind , double blind , and triple blind mean different things to different people . Moreover , many medical research ers confuse blinding with allocation concealment . Such confusion indicates misunderst and ings of both . The term blinding refers to keeping trial participants , investigators ( usually health-care providers ) , or assessors ( those collecting outcome data ) unaware of the assigned intervention , so that they will not be influenced by that knowledge . Blinding usually reduces differential assessment of outcomes ( information bias ) , but can also improve compliance and retention of trial participants while reducing biased supplemental care or treatment ( sometimes called co-intervention ) . Many investigators and readers naïvely consider a r and omised trial as high quality simply because it is double blind , as if double-blinding is the sine qua non of a r and omised controlled trial . Although double blinding ( blinding investigators , participants , and outcome assessors ) indicates a strong design , trials that are not double blinded should not automatically be deemed inferior . Rather than solely relying on terminology like double blinding , research ers should explicitly state who was blinded , and how . We recommend placing greater credence in results when investigators at least blind outcome assessment s , except with objective outcomes , such as death , which leave little room for bias . If investigators properly report their blinding efforts , readers can judge them . Unfortunately , many articles do not contain proper reporting . If an article cl aims blinding without any accompanying clarification , readers should remain sceptical about its effect on bias reduction OBJECTIVES To investigate whether coinciding peak serum caffeine concentration with the onset of exercise enhances subsequent endurance performance . DESIGN R and omised , double-blind , crossover . METHODS In this r and omised , placebo-controlled , double-blind crossover study , 14 male trained cyclists and triathletes ( age 31±5year , body mass 75.4±5.7 kg , VO₂max 69.5±6.1 mL kg⁻¹ min⁻¹ and peak power output 417±35W , mean±SD ) consumed 6 mg kg(-1 ) caffeine or a placebo either 1h ( C(1h ) ) prior to completing a 40 km time trial or when the start of exercise coincided with individual peak serum caffeine concentrations ( C(peak ) ) . C(peak ) was determined from a separate ' caffeine profiling ' session that involved monitoring caffeine concentrations in the blood every 30 min over a 4h period . RESULTS Following caffeine ingestion , peak serum caffeine occurred 120 min in 12 participants and 150 min in 2 participants . Time to complete the 40 km time trial was significantly faster ( 2.0 % ; p=0.002 ) in C(1h ) compared to placebo . No statistically significant improvement in performance was noted in the C(peak ) trial versus placebo ( 1.1 % ; p=0.240 ) . Whilst no differences in metabolic markers were found between C(peak ) and placebo conditions , plasma concentrations of glucose ( p=0.005 ) , norepinephrine and epinephrine ( p≤0.002 ) were higher in the C(1h ) trial 6 min post-exercise versus placebo . CONCLUSIONS In contrast to coinciding peak serum caffeine concentration with exercise onset , caffeine consumed 60 min prior to exercise result ed in significant improvements in 40 km time trial performance . The ergogenic effect of caffeine was not found to be related to peak caffeine concentration in the blood at the onset of endurance exercise This double-blind , within-subjects experiment examined the effects of acute caffeine ingestion on perceptions of muscle pain following a bout of high-intensity , upper-body resistance exercise to failure . Moderately trained males ( N.=18 ) ingested a dose of caffeine ( 5 mg · kg-1 ) or placebo in a r and omised and counterbalanced order and 1 hour later completed bench press exercise to failure at an intensity of 60 % 1 repetition maximum . Repetitions completed was taken as a measure of performance , peak heart rate was determined via heart rate telemetry during the exercise bout , rating of perceived exertion ( RPE ) and upper body muscle pain was recorded immediately upon failure of the exercise task and peak blood lactate concentration was determined post-exercise . Caffeine result ed in improved repetitions to failure ( t [17]=3.119 , P=0.006 ) , greater peak blood lactate ( t [ 17 ] = 5.080 , P=0.0001 ) and lower RPE ( t 17=-3.431 , P=0.003 ) compared to placebo . Muscle pain perception was also significantly lower in the caffeine condition compared to placebo ( t [17]=-2.567 , P=0.04 ) . These results support prior studies using aerobic based exercise modes in suggesting that caffeine ingestion can dampen exercise-induced muscle pain . Specifically , caffeine ingestion enhances muscular strength performance and reduces upper body muscle pain perception immediately following a bout of high-intensity resistance exercise to failure Background Research has indicated that low-to-moderate dosages of caffeine supplementation are ergogenic for sustained endurance efforts as well as high-intensity exercise . The effects of caffeine supplementation on strength-power performance are equivocal , with some studies indicating a benefit and others demonstrating no change in performance . The majority of research that has examined the effects of caffeine supplementation on strength-power performance has been carried out in both trained and untrained men . Therefore , the purpose of this study was to determine the acute effects of caffeine supplementation on strength and muscular endurance in resistance-trained women . Methods In a r and omized manner , 15 women consumed caffeine ( 6 mg/kg ) or placebo ( PL ) seven days apart . Sixty min following supplementation , participants performed a one-repetition maximum ( 1RM ) barbell bench press test and repetitions to failure at 60 % of 1RM . Heart rate ( HR ) and blood pressure ( BP ) were assessed at rest , 60 minutes post-consumption , and immediately following completion of repetitions to failure . Results Repeated measures ANOVA indicated a significantly greater bench press maximum with caffeine ( p ≤ 0.05 ) ( 52.9 ± 11.1 kg vs. 52.1 ± 11.7 kg ) with no significant differences between conditions in 60 % 1RM repetitions ( p = 0.81 ) . Systolic blood pressure was significantly greater post-exercise , with caffeine ( p < 0.05 ) ( 116.8 ± 5.3 mmHg vs. 112.9 ± 4.9 mmHg ) . Conclusions These findings indicate a moderate dose of caffeine may be sufficient for enhancing strength performance in resistance-trained women Background The objective of this study was to analyze the effect of caffeine ingestion on the performance and physiological variables associated with fatigue in 20-km cycling time trials . Methods In a double-blind placebo-controlled crossover study , 13 male cyclists ( 26–10 y , 71–9 kg , 176–6 cm ) were r and omized into 2 groups and received caffeine ( CAF ) capsules ( 6 mg.kg–1 ) or placebo ( PLA ) 60 min before performing 20-km time trials . Distance , speed , power , rpm , rating of perceived exertion ( RPE ) , electromyography ( EMG ) of the quadriceps muscles and heart rate ( HR ) were continuously measured during the tests . In addition , BRUMS question naire was applied before and after the tests . Results Significant interactions were found in power and speed ( P=0.001 ) , which were significantly higher at the end of the test ( final 2 km ) after CAF condition . A main effect of time ( P=0.001 ) was observed for RPE and HR , which increased linearly until the end of exercise in both conditions . The time taken to complete the test was similar in both conditions ( PLA=2191–158 s vs. CAF=2181–194 s , P=0.61 ) . No significant differences between CAF and PLA conditions were identified for speed , power , rpm , RPE , EMG , HR , and BRUMS ( P>0.05 ) . Conclusion The results suggest that caffeine intake 60 min before 20-km time trials has no effect on the performance or physiological responses of cyclists Background The purpose of this study was to examine the ergogenic benefits of Turkish coffee consumed an hour before exercise . In addition , metabolic , cardiovascular , and subjective measures of energy , focus and alertness were examined in healthy , recreationally active adults who were regular caffeine consumers ( > 200 mg per day ) . Methods Twenty males ( n = 10 ) and females ( n = 10 ) , age 24.1 ± 2.9 y ; height 1.70 ± 0.09 m ; body mass 73.0 ± 13.0 kg ( mean ± SD ) , ingested both Turkish coffee [ 3 mg · kg−1 BW of caffeine , ( TC ) ] , and decaffeinated Turkish coffee ( DC ) in a double-blind , r and omized , cross-over design . Performance measures included a 5 km time trial , upper and lower body reaction to visual stimuli , and multiple object tracking . Plasma caffeine concentrations , blood pressure ( BP ) , heart rate and subjective measures of energy , focus and alertness were assessed at baseline ( BL ) , 30-min following coffee ingestion ( 30 + ) , prior to endurance exercise ( PRE ) and immediately-post 5 km ( IP ) . Metabolic measures [ VO2 , VE , and respiratory exchange rate ( RER ) ] were measured during the 5 km . Results Plasma caffeine concentrations were significantly greater during TC ( p < 0.001 ) at 30 + , PRE , and IP compared to DC . Significantly higher energy levels were reported at 30 + and PRE for TC compared to DC . Upper body reaction performance ( p = 0.023 ) and RER ( p = 0.019 ) were significantly higher for TC ( 85.1 ± 11.6 “ hits , ” and 0.98 ± 0.05 respectively ) compared to DC ( 81.2 ± 13.7 “ hits , ” and 0.96 ± 0.05 , respectively ) . Although no significant differences ( p = 0.192 ) were observed in 5 km run time , 12 of the 20 subjects ran faster ( p = 0.012 ) during TC ( 1662 ± 252 s ) compared to DC ( 1743 ± 296 s ) . Systolic BP was significantly elevated during TC in comparison to DC . No other differences ( p > 0.05 ) were noted in any of the other performance or metabolic measures . Conclusions Acute ingestion of TC result ed in a significant elevation in plasma caffeine concentrations within 30-min of consumption . TC ingestion result ed in significant performance benefits in reaction time and an increase in subjective feelings of energy in habitual caffeine users . No significant differences were noted in time for the 5 km between trials , however 60 % of the participants performed the 5 km faster during the TC trial and were deemed responders . When comparing TC to DC in responders only , significantly faster times were noted when consuming TC compared to DC . No significant benefits were noted in measures of cognitive function The purpose of the present study was to investigate the effects of caffeine ingestion on pacing strategy and energy expenditure during a 4000-m cycling time-trial ( TT ) . Eight recreationally-trained male cyclists volunteered and performed a maximal incremental test and a familiarization test on their first and second visits , respectively . On the third and fourth visits , the participants performed a 4000-m cycling TT after ingesting capsules containing either caffeine ( 5 mg.kg−1 of body weight , CAF ) or cellulose ( PLA ) . The tests were applied in a double-blind , r and omized , repeated- measures , cross-over design . When compared to PLA , CAF ingestion increased mean power output [ 219.1±18.6 vs. 232.8±21.4 W ; effect size ( ES ) = 0.60 ( 95 % CI = 0.05 to 1.16 ) , p = 0.034 ] and reduced the total time [ 419±13 vs. 409±12 s ; ES = −0.71 ( 95 % CI = −0.09 to −1.13 ) , p = 0.026 ] . Furthermore , anaerobic contribution during the 2200- , 2400- , and 2600-m intervals was significantly greater in CAF than in PLA ( p<0.05 ) . However , the mean anaerobic [ 64.9±20.1 vs. 57.3±17.5 W ] and aerobic [ 167.9±4.3 vs. 161.8±11.2 W ] contributions were similar between conditions ( p>0.05 ) . Similarly , there were no significant differences between CAF and PLA for anaerobic work ( 26363±7361 vs. 23888±6795 J ) , aerobic work ( 68709±2118 vs. 67739±3912 J ) , or total work ( 95245±8593 vs. 91789±7709 J ) , respectively . There was no difference for integrated electromyography , blood lactate concentration , heart rate , and ratings of perceived exertion between the conditions . These results suggest that caffeine increases the anaerobic contribution in the middle of the time trial , result ing in enhanced overall performance Abstract Hurley , CF , Hatfield , DL , and Riebe , DA . The effect of caffeine ingestion on delayed onset muscle soreness . J Strength Cond Res 27(11 ) : 3101–3109 , 2013—The beneficial effects of caffeine on aerobic activity and resistance training performance are well documented . However , less is known concerning caffeine 's potential role in reducing perception of pain and soreness during exercise . In addition , there is no information regarding the effects of caffeine on delayed onset muscle soreness ( DOMS ) . The primary purpose of this study was to examine the effect of caffeine ingestion on muscle soreness , blood enzyme activity , and performance after a bout of elbow flexion/extension exercise . Nine low-caffeine – consuming males ( body mass : 76.68 ± 8.13 kg ; height : 179.18 ± 9.35 cm ; age : 20 ± 1 year ) were r and omly assigned to ingest either caffeine or placebo 1 hour before completing 4 sets of 10 bicep curls on a preacher bench , followed by a fifth set in which subjects completed as many repetitions as possible . Soreness and soreness on palpation intensity were measured using three 0–10 visual analog scales before exercise , and 24 , 48 , 72 , 96 , and 120 hours after exercise . After a washout period , subjects crossed over to the other treatment group . Caffeine ingestion result ed in significantly ( p ⩽ 0.05 ) lower levels of soreness on day 2 and day 3 compared with placebo . Total repetitions in the final set of exercise increased with caffeine ingestion compared with placebo . This study demonstrates that caffeine ingestion immediately before an upper-body resistance training out enhances performance . A further beneficial effect of sustained caffeine ingestion in the days after the exercise bout is an attenuation of DOMS . This decreased perception of soreness in the days after a strenuous resistance training workout may allow individuals to increase the number of training sessions in a given time period PURPOSE The purpose of this study was to investigate the effects of ingesting caffeine ( C ) , ephedrine ( E ) , and their combination on muscular endurance , using a double-blind , repeated measures design . METHODS Ninety minutes after ingesting either C ( 4 mg x kg-1 ) , E ( 0.8 mg x kg-1 ) , a combination of C+E , or a placebo ( P ) , 13 male subjects performed a weight-training circuit consisting of three supersets ( SS ) , each SS consisting of leg press ( at 80 % of 1 RM to exhaustion ) followed by bench press ( at 70 % 1-RM to exhaustion ) ; 2 min of rest intervened between SS . RESULTS The trials involving ephedrine ingestion ( C+E and E ) , when compared with the nonephedrine trials ( C and P ) , caused significant increases ( P < 0.05 ) in the mean number of repetitions completed for both the leg-press and bench-press exercises but only during the first SS . During that first set , the mean number ( + /-SD ) of repetitions for leg press was 19 + /- 8 , 16 + /- 7 , 14 + /- 6 , and 13 + /- 5 for the C+E , E , C , and P trials , respectively . The mean numbers of repetitions for the first set of bench-press exercise were 14 + /- 3 , 13 + /- 3 , 12 + /- 3 , and 12 + /- 3 for the C+E , E , C , and P trials , respectively . As a result , the total weight lifted during all three sets was greater for the trials involving ephedrine ingestion . Systolic blood pressure before exercise was significantly increased with both ephedrine treatment trials when compared with the other trials ( C+E = 156 + /- 29 mm Hg ; E = 150 + /- 14 ; C = 141 + /- 16 ; P = 138 + /- 14 ) . CONCLUSION It was concluded that acute ingestion of C+E and E increases muscular endurance during the first set of traditional resistance-training exercise . The performance enhancement was attributed primarily to the effects of E ; there was no additive effect of Abstract Previous experiments found that placebos produced small decreases in neural activity of pain‐related areas of the brain , yet decreases were only statistically significant after termination of stimuli and in proximity to when subjects rated them . These changes could reflect report bias rather than analgesia . This functional magnetic resonance imaging ( fMRI ) study examined whether placebo analgesia is accompanied by reductions in neural activity in pain‐related areas of the brain during the time of stimulation . Brain activity of irritable bowel syndrome patients was measured in response to rectal distension by a balloon barostat . Large reductions in pain and in brain activation within pain‐related regions ( thalamus , somatosensory cortices , insula , and anterior cingulate cortex ) occurred during the placebo condition . Results indicate that decreases in activity were related to placebo suggestion and a second factor ( habituation/attention/conditioning ) . Although many factors influence placebo analgesia , it is accompanied by reduction in pain processing within the brain in clinical ly relevant conditions This study investigated the ergogenic effects of a commercial energy drink ( Red Bull ) or an equivalent dose of anhydrous caffeine in comparison with a noncaffeinated control beverage on cycling performance . Eleven trained male cyclists ( 31.7 ± 5.9 y 82.3 ± 6.1 kg , VO2max = 60.3 ± 7.8 mL · kg-1 · min-1 ) participated in a double-blind , placebo-controlled , crossover- design study involving 3 experimental conditions . Participants were r and omly administered Red Bull ( 9.4 mL/kg body mass [ BM ] containing 3 mg/kg BM caffeine ) , anhydrous caffeine ( 3 mg/kg BM given in capsule form ) , or a placebo 90 min before commencing a time trial equivalent to 1 h cycling at 75 % peak power output . Carbohydrate and fluid volumes were matched across all trials . Performance improved by 109 ± 153 s ( 2.8 % , P = .039 ) after Red Bull compared with placebo and by 120 ± 172 s ( 3.1 % , P = .043 ) after caffeine compared with placebo . No significant difference ( P > .05 ) in performance time was detected between Red Bull and caffeine treatments . There was no significant difference ( P > .05 ) in mean heart rate or rating of perceived exertion among the 3 treatments . This study demonstrated that a moderate dose of caffeine consumed as either Red Bull or in anhydrous form enhanced cycling time-trial performance . The ergogenic benefits of Red Bull energy drink are therefore most likely due to the effects of caffeine , with the other ingredients not likely to offer additional benefit PURPOSE The placebo effect-a change attributable only to an individual 's belief in the efficacy of a treatment-might provide a worthwhile improvement in physical performance . Although sports scientists account for placebo effects by blinding subjects to treatments , little research has sought to quantify and explain the effect itself . The present study explored the placebo effect in laboratory cycling performance using quantitative and qualitative methods . METHOD Six well-trained male cyclists undertook two baseline and three experimental 10-km time trials . Subjects were informed that in the experimental trials they would each receive a placebo , 4.5 mg.kg caffeine , and 9.0 mg.kg caffeine , r and omly assigned . However , placebos were administered in all experimental conditions . Semistructured interviews were also conducted to explore subjects ' experience of the effects of the capsules before and after revealing the deception . RESULTS A likely trivial increase in mean power of 1.0 % over baseline was associated with experimental trials ( 95 % confidence limits , -1.4 to 3.6 % ) , rising to a likely beneficial 2.2 % increase in power associated with experimental trials in which subjects believed they had ingested caffeine ( -0.8 to 5.4 % ) . A dose-response relationship was evident in experimental trials , with subjects producing 1.4 % less power than at baseline when they believed they had ingested a placebo ( -4.6 to 1.9 % ) , 1.3 % more power than at baseline when they believed they had ingested 4.5 mg.kg caffeine ( -1.4 to 4.1 % ) , and 3.1 % more power than at baseline when they believed they had ingested 9.0 mg.kg caffeine ( -0.4 to 6.7 % ) . All subjects reported caffeine-related symptoms . CONCLUSIONS Quantitative and qualitative data suggest that placebo effects are associated with the administration of caffeine and that these effects may directly or indirectly enhance performance in well-trained cyclists PURPOSE To determine whether a dose-response relationship exists between caffeine and 2000-m rowing performance . METHODS In this r and omized , placebo-controlled , double-blind crossover study , 10 competitive male rowers ( mean + /- SD : age = 20.6 + /- 1.4 yr , body mass = 87.7 + /- 10.5 kg , height = 186.8 + /- 6.8 cm , (.)VO2peak = 5.1 + /- 0.6 L x min(-1 ) ) consumed 2 , 4 , or 6 mg x kg(-1 ) caffeine or a placebo 60 min before completing a 2000-m time trial on a rowing ergometer . The trials were preceded by a 24-h st and ardized diet ( including a light preexercise meal of 2 g x kg(-1 ) CHO ) , and subjects were tested preexercise for hydration , caffeine abstinence , and blood glucose concentrations . RESULTS Time trial performance was not significantly different across the three caffeine doses or placebo ( P = 0.249 ) . After the three caffeine trials , postexercise plasma glucose and lactate concentrations were higher compared with the placebo trial ( P < 0.05 ) . Plasma caffeine concentrations after 60 min of ingestion were lower than the values reported previously by others following the same dose , and there was considerable interindividual variation in plasma caffeine concentrations in response to the various caffeine doses . CONCLUSIONS The large interindividual response to the caffeine doses suggests that individual characteristics need to be considered when administering caffeine for performance enhancement . In addition , preexercise feeding may significantly affect plasma caffeine concentrations and the potential for caffeine to improve performance OBJECTIVE Prior investigations have failed to find reliable personality differences in placebo responding . The present study tests the hypothesis that personality and situational variables interact to determine placebo responding . METHODS Optimists and pessimists were r and omly assigned to one of three conditions . In the first condition , the participants were told that they were to ingest a pill that would make them feel unpleasant ( deceptive-expectation group ) . In the second condition , the participants were told that they were to ingest a pill that would make them feel either unpleasant or was an inactive substance ( conditional-expectation group ) . Finally , a third group was told they were to ingest a pill that was inactive ( control group ) . RESULTS Pessimists were more likely than optimists to follow a negative-placebo expectation when given a deceptive expectation , but not when given a conditional expectation . CONCLUSION The personality variable optimism-pessimism relates to placebo responding when individuals are given a deceptive but not a conditional expectation . This suggests that personality and situational variables interact to determine placebo responding PURPOSE Caffeine ( CAF ) improves performance in both short- and long- duration running and cycling where performance relies on power output and endurance capacity of leg muscles . No studies have so far tested the effects of CAF while using the double-poling ( DP ) technique in cross-country skiing . When using the DP technique , arm muscles provide the speed-generating force and therefore play an important role in performance outcome . The metabolism of arm muscles differs from that of leg muscles . Thus , results from studies on leg muscles and CAF may not be directly applicable to exercises while using the DP technique in cross-country skiing . The purpose of our study was therefore to investigate the effects of CAF on exercise performance in DP . METHOD Ten highly trained male cross-country skiers ( V·O 2max running , 69.3 ± 1.0 mL · kg · min(-1 ) ) performed a placebo ( PLA ) and CAF trial using a r and omized , double-blind , crossover design . Performance was assessed by measuring the time to complete an 8-km cross-country DP performance test ( C-PT ) . CAF ( 6 mg · kg(-1 ) ) or PLA was ingested 75 min before the C-PT . RESULTS CAF ingestion reduced the time to complete the 8-km C-PT from 34:26 ± 1:25 to 33:01 ± 1:24 min ( P < 0.05 ) . The subjects maintained higher speed and HR throughout the C-PT , and lactate was higher immediately after the C-PT with CAF exposure compared with PLA . Subjects reported lower RPE at submaximal intensities during CAF compared with PLA , although HR was similar . CONCLUSION CAF intake enhances endurance performance in an 8-km C-PT , where arm muscles limit performance . CAF ingestion allowed the participants to exercise with a higher HR and work intensity possibly by reducing perception of effort or facilitating motor unit recruitment Abstract Scientific information about the effects of caffeine intake on combat sport performance is scarce and controversial . The aim of this study was to investigate the effectiveness of caffeine to improve Brazilian Jiu-jitsu (BJJ)-specific muscular performance . Fourteen male and elite BJJ athletes ( 29.2 ± 3.3 years ; 71.3 ± 9.1 kg ) participated in a r and omized double-blind , placebo-controlled and crossover experiment . In two different sessions , BJJ athletes ingested 3 mg kg−1 of caffeine or a placebo . After 60 min , they performed a h and grip maximal force test , a countermovement jump , a maximal static lift test and bench-press tests consisting of one-repetition maximum , power-load , and repetitions to failure . In comparison to the placebo , the ingestion of the caffeine increased : h and grip force in both h and s ( 50.9 ± 2.9 vs. 53.3 ± 3.1 kg ; respectively p < .05 ) , countermovement jump height ( 40.6 ± 2.6 vs. 41.7 ± 3.1 cm ; p = .02 ) , and time recorded in the maximal static lift test ( 54.4 ± 13.4 vs. 59.2 ± 11.9 s ; p < .01).The caffeine also increased the one-repetition maximum ( 90.5 ± 7.7 vs. 93.3 ± 7.5 kg ; p = .02 ) , maximal power obtained during the power-load test ( 750.5 ± 154.7 vs. 826.9 ± 163.7 W ; p < .01 ) and mean power during the bench-press exercise test to failure ( 280.2 ± 52.5 vs. 312.2 ± 78.3 W ; p = .04 ) . In conclusion , the pre-exercise ingestion of 3 mg kg−1 of caffeine increased dynamic and isometric muscular force , power , and endurance strength in elite BJJ athletes . Thus , caffeine might be an effective ergogenic aid to improve physical performance in BJJ A hot and humid environment can be detrimental to race performance . Caffeine , on the other h and , has been shown to be an ergogenic aid for improving endurance performance . To examine the influence of caffeine ingestion on race performance during high heat stress , seven endurance trained competitive road racers aged between 23 and 51 years ( five men , two women ) performed three maximal effort 21-km road races outdoors in hot and humid conditions . The caffeine dose , r and omly assigned in a double-blind fashion , consisted of either 0 , 5 , or 9 mg · kg−1 body mass . During each run , the subjects were allowed to drink waterad libitum at each 5-km point . Blood sample s were obtained immediately before and after each run and analysed for changes in concentrations of Na+ , K+ , glucose , lactate , and hematocrit . Pre and postrun data were also collected for body mass and tympanic membrane temperature . Race times were not significantly different among the races or caffeine doses , with the average times within 1.1 % of each other . In addition , none of the other variables measured varied significantly among the races or caffeine doses . In summary , caffeine intake did not affect race performance . Therefore it was concluded from our study that caffeine is not of ergogenic benefit in endurance races during high heat stress Beck , TW , Housh , TJ , Malek , MH , Mielke , M , and Hendrix , R. The acute effects of a caffeine-containing supplement on bench press strength and time to running exhaustion . J Strength Cond Res 22(5 ) : 1654 - 1658 , 2008-The purpose of the present study was to examine the acute effects of a caffeine-containing supplement ( SUPP ) on one-repetition maximum ( 1-RM ) bench press strength and time to running exhaustion ( TRE ) at a velocity that corresponded to 85 % of the peak oxygen uptake ( & OV0312;O2peak ) . The study used a double-blinded , placebo-controlled , crossover design . Thirty-one men ( mean ± SD age = 23.0 ± 2.6 years ) were r and omly assigned to take either the SUPP or placebo ( PLAC ) first . The SUPP contained 201 mg of caffeine , and the PLAC was microcrystalline cellulose . All subjects were tested for 1-RM bench press strength and TRE at 45 minutes after taking either the SUPP or PLAC . After 1 week of rest , the subjects returned to the laboratory and ingested the opposite substance ( SUPP or PLAC ) from what was taken during the previous visit . The 1-RM bench press and TRE tests were then performed in the same manner as before . The results indicated that the SUPP had no effect on 1-RM bench press strength or TRE at 85 % & OV0312;O2peak . It is possible that the acute effects of caffeine are affected by differences in training status and /or the relative intensity of the exercise task . Future studies should examine these issues , in addition to testing the acute effects of various caffeine doses on performance during maximal strength , power , and aerobic activities . These findings do not , however , support the use of caffeine as an ergogenic aid in untrained to moderately trained individuals The purpose of this study was to evaluate the potential ergogenic benefit of caffeine in the performance of a 1,500-meter swim . Caffeine ( 6 mg.kg-1 ) or placebo was administered 2 - 1/2 hrs prior to the swim trial in a double-blind crossover design . Caffeine result ed in a significantly lower perceived exertion for 100-m warm-up swims . Subjects swam significantly ( p < 0.05 ) faster with caffeine ( 20:58.8 + /- 0:36.4 , mean + /- SEM ) than without ( 21:21.8 + /- 0:38 ) . Plasma potassium was significantly lower prior to the swim with caffeine , and blood glucose was higher after that swim . Caffeine provides an ergogenic benefit for a 1,500-meter swim , an event that is completed in less than 25 min . Lower plasma potassium concentration prior to exercise and higher blood glucose following the trial suggest that electrolyte balance and glucose availability may be important aspects of the ergogenic effects of caffeine The purpose of this study was to investigate if caffeine ingestion improves 5-km time-trial performance in well-trained and recreational runners . Using a double-blind placebo-controlled design , 15 well-trained and 15 recreational runners completed two r and omized 5-km time-trials , after ingestion of either 5mgkg(-1 ) of caffeine or a placebo . Caffeine ingestion significantly improved 5-km running performance in both the well-trained and recreational runners . In comparison to the placebo trial , the caffeine trial result ed in 1.1 % ( 90 % CI 0.4 - 1.6 ) and 1.0 % ( 0.2 - 2 % ) faster times for the well-trained and recreational runners . Reliability testing of the recreational runners indicated a test-retest error of measurement of 1.4 % . We conclude that caffeine ingestion is likely to produce small but significant gains in 5-km running performance for both well-trained and recreational runners Background : Ergogenic effects of caffeine ( CAF ) ingestion have been observed in different cycling exercise modes , and have been associated with alterations in ratings of perceived exertion ( RPE ) . However , there has been little investigation of maximal oxygen uptake ( VO2MAX ) test outcomes . Aim : This study aim ed to verify whether CAF may reduce RPE , thereby improving maximal incremental test ( MIT ) outcomes such as VO2MAX , time to exhaustion and peak power output ( WPEAK ) . Methods : Nine healthy individuals performed three MITs ( 25 W/min until exhaustion ) in a r and om , counterbalanced fashion after ingestion of CAF , placebo perceived as caffeine ( PLA ) , and no supplementation ( baseline control ) . VO2 was measured throughout the test , while RPE was rated according to overall and leg effort sensations . The power output corresponding to submaximal ( RPE = 14 according to the 6–20 Borg scale ) and maximal RPE was recorded for both overall ( O-RPE14 and O-RPEMAX ) and leg RPE ( L-RPE14 and L-RPEMAX ) . Results : VO2MAX did not change significantly between MITs ; however , CAF and PLA increased time to exhaustion ( ↑ ∼18.7 % and ∼17.1 % , respectively ; p < .05 ) and WPEAK ( ↑ ∼13.0 % and ∼11.8 % , respectively ; p < .05 ) when compared with control . When compared with control , CAF ingestion reduced submaximal and maximal overall and leg RPEs , the effect being greater in maximal ( likely beneficial in O-RPEMAX and L-RPEMAX ) than submaximal RPE ( possibly beneficial in O-RPE14 and L-RPE14 ) . Similar results were found when participants ingested PLA . Conclusions : Compared with control , CAF and PLA improved MIT performance outcomes such as time to exhaustion and WPEAK , without altering VO2MAX values . CAF effects were attributed to placebo Multiple studies corroborate the ergogenic properties of caffeine ( CAF ) for endurance performance , yet fewer investigations document the efficacy of acute caffeine intake for intense , short-term exercise . The aim of the study was to determine the ergogenic potential of caffeine during testing of muscular strength and endurance . Twenty-two resistance-trained men ingested CAF ( 6 mg/kg ) or placebo ( PL ) 1 h pre-exercise in a r and omized , double-blind crossover design . They refrained from caffeine intake and strenuous exercise 48 and 24 h , respectively , pre-visit . Initially , resting heart rate and blood pressure were obtained followed by one-repetition maximum ( 1-RM ) testing on the barbell bench press and leg press . Upon determination of 1-RM , participants completed repetitions to failure at 60%1-RM . Heart rate , blood pressure , and rating of perceived exertion ( RPE ) were measured after the final repetition . Compared to PL , there was no effect ( P > 0.05 ) of caffeine on muscular strength , as 1-RM bench press ( 116.4 ± 23.6 kg vs. 114.9 ± 22.8 kg ) and leg press ( 410.6 ± 92.4 kg vs. 394.8 ± 95.4 kg ) were similar . Total weight lifted during the 60 % 1-RM trial was 11 and 12 % higher for the bench press and leg press with caffeine compared to placebo , yet did not reach significance . RPE was similar at the end of resistance exercise with CAF vs. PL . Acute caffeine intake does not significantly alter muscular strength or endurance during intense bench press or leg press exercise , yet the practical importance of the increased muscular endurance remains to be explored There is limited research on the physiological effects of caffeine ( CAF ) ingestion on exercise performance during acute hypoxia . The aim of the present study was therefore to test the effect of placebo ( PLA ) and CAF ( 4.5 mg/kg ) on double poling ( DP ) performance during acute hypoxia . Thirteen male subelite cross-country skiers ( V̇o2max 72.6 ± 5.68 ml·kg(-1)·min(-1 ) ) were included . Performance was assessed as 1 ) an 8-km cross-country DP time-trial ( C-PT ) , and 2 ) time until task failure at a set workload equal to ∼90 % of DP V̇o2max . Testing was carried out in a hypobaric chamber , at 800 mbar ( Pio2 : ∼125 mmHg ) corresponding to ∼2,000 m above sea level in a r and omized double-blinded , placebo-controlled , cross-over design . CAF improved time to task failure from 6.10 ± 1.40 to 7.22 ± 1.30 min ( P < 0.05 ) and velocity the first 4 km ( P < 0.05 ) but not overall time usage for the 8-km C-PT . During submaximal exercise subjects reported lower pain in arms and rate of perceived exertion ( RPE ) following CAF ingestion . Throughout C-PTs similar RPE and pain was shown between treatments . However , higher heart rate was observed during the CAF 8 km ( 187 ± 7 vs. 185 ± 7 ; P < 0.05 ) and 90 % C-PT ( 185 ± 7 vs. 181 ± 9 ) associated with increased ventilation , blood lactate , glucose , adrenaline , decreased pH , and bicarbonate . The present study demonstrates for the first time that CAF ingestion improves DP time to task failure although not consistently time trial performance during acute exposure to altitude . Mechanisms underpinning improvements seem related to reduced pain RPE and increased heart rate during CAF C-PTs Abstract Stimulus substitution models posit that placebo responses are due to pairings of conditional and unconditional stimuli . Expectancy theory maintains that conditioning trials produce placebo response expectancies , rather than placebo responses , and that the expectancies elicit the responses . We tested these opposing models by providing some participants with information intended to impede the formation of placebo expectancies during conditioning trials and by assessing placebo expectancies . Although conditioning trials significantly enhanced placebo responding , this effect was eliminated by adding expectancies to the regression equation , indicating that the effect of pairing trials on placebo response was mediated completely by expectancy . Verbal information reversed the effect of conditioning trials on both placebo expectancies and placebo responses , and the magnitude of the placebo effect increased significantly over 10 extinction trials . These data disconfirm a stimulus substitution explanation and provide strong support for an expectancy interpretation of the conditioned placebo enhancement produced by these methods Hendrix , CR , Housh , TJ , Mielke , M , Zuniga , JM , Camic , CL , Johnson , GO , Schmidt , RJ , and Housh , DJ . Acute effects of a caffeine-containing supplement on bench press and leg extension strength and time to exhaustion during cycle ergometry . J Strength Cond Res 24(3 ) : 859 - 865 , 2010-The purpose of the present study was to examine the acute effects of a caffeine-containing supplement ( SUPP ) on 1 repetition maximum ( 1RM ) bench press and leg extension strength , as well as time to exhaustion ( TTE ) , during cycle ergometry at a power output that corresponded to 80 % of & OV0312;o2peak . The study used a double-blinded , placebo-controlled , crossover design . Twenty-one untrained men ( mean ± SD age = 23.0 ± 2.6 yr ) were r and omly assigned to take either the SUPP or placebo ( PLAC ) first . The SUPP contained 400 mg of caffeine , 66.7 mg of capsicum extract , 10 mg of bioperine , and 40 mg of niacin , and the PLAC was microcrystalline cellulose . Sixty minutes after taking either the SUPP or PLAC , the subjects were tested for 1RM bench press and leg extension strength , as well as TTE . After 1 week of rest , the subjects ingested the opposite substance ( SUPP or PLAC ) and were retested for 1RM bench press and leg extension strength , as well as TTE . The results indicated that the SUPP had no effect on 1RM bench press strength , 1RM leg extension strength , or TTE at 80 % & OV0312;o2peak . These findings did not support the use of the caffeine-containing SUPP in the present study as an ergogenic aid in untrained individuals The primary aim of this study was to determine the repeatability of caffeine 's ergogenic effects on cycling performance . It was hypothesized that improvements in performance would be similar when caffeine was ingested on 2 separate days . Nine endurance-trained men and women ( mean age and maximal oxygen uptake , 27.4 ± 5.9 years and 57.5 ± 3.9 mL kg⁻¹ min⁻¹ ) initially completed 2 familiarization trials . During 3 subsequent sessions separated by at least 48 hours , the subjects completed a 10-km cycling time trial preceded by ingestion of a drink containing caffeine ( 5 mg/kg ) or placebo . Treatments were ingested using a r and omized , single-blind , crossover design , and the subjects were deceived as to the specific content of all drinks . During exercise , heart rate , rating of perceived exertion , and time were recorded every 1.6 km . Repeated- measures analysis of variance was used to compare the differences in variables across distance and treatment . In both caffeine trials , caffeine increased ( P = .02 ) cycling performance by 1.6 % and 1.9 % vs placebo ( 16.98 ± 0.96 and 16.92 ± 0.97 minutes with caffeine vs 17.25 ± 0.96 minutes in placebo ) , and 7 of 9 subjects revealed improved performance . The mean performance improvement in the caffeine trials was similar ( P = .35 ; -0.27 and -0.32 minutes , respectively ) across days . Heart rate during exercise was higher ( P b .001 ) with caffeine vs placebo , although the rating of perceived exertion was similar ( P = .65 ) . Data reveal that caffeine 's ergogenic effects on cycling performance are repeatable across days , yet some individuals did not exhibit improved performance with caffeine PURPOSE To compare the acute effect of caffeine ingestion on performance in young judo athletes . METHOD In a r and omized double-blind design , eighteen judo athletes ( 16.1 ± 1.4 yrs . ) were evaluated on three nonconsecutive days . On the first day , the special judo fitness test ( SJFT ) was used as a control session . On the second day , the sample was r and omly divided into two equal groups . One group received 4 mg.kg-1 of caffeine ( capsule ) and the other group received a placebo . After resting for 60 min , the sample performed the SJFT . On the final day of testing , the same procedure was performed but the substance ingested was exchanged between the groups . RESULTS Heart rate ( HR ) and rating of perceived exertion ( RPE ) were recorded throughout the applications of the SJFTs . Caffeine ingestion did not induce changes in HR , but reduced the RPE compared with the placebo session ( 7.0 ± 1.1 vs 8.2 ± 2.0 ; p < .05 ) , increased the number of throws applied ( 29.0 ± 2.6 vs 22.1 ± 3.4 ; p < .01 ) and reduced the SJFT index ( 12.2 ± 0.5 vs. 15.7 ± 0.9 ; p < .001 ) . CONCLUSION 4 mg.kg-1 did not alter HR but improved performance on SJFT in young judo athletes and reduced the RPE The ergogenic effect of caffeine on endurance exercise is commonly accepted . We aim ed to eluci date realistically the effect of caffeine on triathlon event performance using a field study design , while allowing investigation into potential mechanisms at play . A double-blind , r and omized , crossover field trial was conducted . Twenty-six triathletes ( 14 males and 12 females ; mean ± SD : age = 37.8 ± 10.6 years , habitual caffeine intake = 413 ± 505 mg/day , percentage body fat = 14.5 ± 7.2 % , and training/week = 12.8 ± 4.5 hr ) participated in this study . Microencapsulated caffeine ( 6 mg/kg body weight ) was supplemented 60 min pretrial . Performance data included time to completion , rating of perceived exertion , and profile of mood states . Blood sample s taken before , during , and postrace were analyzed for cortisol , testosterone , and full blood count . Capillary blood lactate concentrations were assessed prerace , during transitions , and 3 , 6 , 9 , 12 , and 15 min after triathlons . Caffeine supplementation result ed in a 3.7 % reduction in swim time ( 33.5 ± 7.0 vs. 34.8 ± 8.1 min , p < .05 ) and a 1.3 % reduction in time to completion ( 149.6 ± 19.8 vs. 151.5 ± 18.6 min , p < .05 ) for the whole group . Gender differences and individual responses are also presented . Caffeine did not alter the rating of perceived exertion significantly , but better performance after caffeine supplementation suggests a central effect result ing in greater overall exercise intensity at the same rating of perceived exertion . Caffeine supplementation was associated with higher postexercise cortisol levels ( 665 ± 200 vs. 543 ± 169 nmol/L , p < .0001 ) and facilitated greater peak blood lactate accumulation ( analysis of variance main effect , p < .05 ) . We recommend that triathlon athletes with relatively low habitual caffeine intake may ingest 6 mg/kg body weight caffeine , 45 - 60 min before the start of Olympic-distance triathlon to improve their performance Abstract Glaister , M , Pattison , JR , Muniz-Pumares , D , Patterson , SD , and Foley , P. Effects of dietary nitrate , caffeine , and their combination on 20-km cycling time trial performance . J Strength Cond Res 29(1 ) : 165–174 , 2015—The aim of this study was to examine the acute supplementation effects of dietary nitrate , caffeine , and their combination on 20-km cycling time trial performance . Using a r and omized , counterbalanced , double-blind Latin-square design , 14 competitive female cyclists ( age : 31 ± 7 years ; height : 1.69 ± 0.07 m ; body mass : 61.6 ± 6.0 kg ) completed four 20-km time trials on a racing bicycle fitted to a turbo trainer . Approximately 2.5 hours before each trial , subjects consumed a 70-ml dose of concentrated beetroot juice containing either 0.45 g of dietary nitrate or with the nitrate content removed ( placebo ) . One hour before each trial , subjects consumed a capsule containing either 5 mg·kg−1 of caffeine or maltodextrin ( placebo ) . There was a significant effect of supplementation on power output ( p = 0.001 ) , with post hoc tests revealing higher power outputs in caffeine ( 205 ± 21 W ) vs. nitrate ( 194 ± 22 W ) and placebo ( 194 ± 25 W ) trials only . Caffeine-induced improvements in power output corresponded with significantly higher measures of heart rate ( caffeine : 166 ± 12 b·min−1 vs. placebo : 159 ± 15 b·min−1 ; p = 0.02 ) , blood lactate ( caffeine : 6.54 ± 2.40 mmol·L−1 vs. placebo : 4.50 ± 2.11 mmol·L−1 ; p < 0.001 ) , and respiratory exchange ratio ( caffeine : 0.95 ± 0.04 vs. placebo : 0.91 ± 0.05 ; p = 0.03 ) . There were no effects ( p ≥ 0.05 ) of supplementation on cycling cadence , rating of perceived exertion , , or integrated electromyographic activity . The results of this study support the well-established beneficial effects of caffeine supplementation on endurance performance . In contrast , acute supplementation with dietary nitrate seems to have no effect on endurance performance and adds nothing to the benefits afforded by caffeine supplementation Purpose We investigated associations between athletes ’ use of sport supplements and their responsiveness to placebo and nocebo interventions . Methods Participants ( n = 627 ) reported their intention to use , and actual use of , sport supplements . They then completed a 5 × 20 m repeat sprint protocol in the baseline condition , before being r and omized to one of three treatments . Participants in the positive-belief treatment were administered an inert capsule described as a potent supplement which would improve sprint performance . Participants in the negative-belief treatment were administered an inert capsule described as a potent supplement which would negatively affect sprint performance . Participants in the control treatment received neither instruction nor capsule . Twenty minutes after baseline trials , all participants completed the same repeat sprint protocol in the experimental condition . Results Compared with controls , no mean differences in performance were observed between baseline and experimental conditions for the positive-belief treatment ( −0.07 % ± 0.27 % , d = 0.02 ) , but mean differences were observed for the negative-belief treatment ( −0.92 % ± 0.31 % , d = 0.32 ) , suggesting a moderate nocebo effect . In the positive-belief treatment , however , a relationship between intention to use supplements and performance was observed . Performance worsened by −1.10 % ± 0.30 % compared with baseline for participants not intending to use supplements , worsened by −0.64 % ± 0.43 % among those undecided about supplement use , but improved by 0.19 % ± 0.24 % among those participants intending to use supplements . Conclusions Information about a harmful supplement worsened repeat sprint performance ( a mean nocebo effect ) , whereas information about a beneficial supplement did not improve performance ( no mean placebo effect was observed ) . However , participants ' intention to use sport supplements influenced the direction and magnitude of subsequent placebo responses , with participants intending to use supplements more likely to respond to the positive intervention Abstract The efficacy of caffeine ingestion in enhancing aerobic performance is well established . However , despite suggestions that caffeine may enhance resistance exercise performance , research is equivocal on the effect of acute caffeine ingestion on resistance exercise performance . It has also been suggested that dampened perception of perceived exertion and pain perception might be an explanation for any possible enhancement of resistance exercise performance due to caffeine ingestion . Therefore , the aim of this study was to examine the acute effect of caffeine ingestion on repetitions to failure , rating of perceived exertion ( RPE ) and muscle pain perception during resistance exercise to failure . Eleven resistance trained individuals ( 9 males , 2 females , mean age±SD=26.4±6.4 years ) , took part in this double-blind , r and omised cross-over experimental study whereby they ingested a caffeinated ( 5 mg kg−1 ) or placebo solution 60 minutes before completing a bout of resistance exercise . Experimental conditions were separated by at least 48 hours . Resistance exercise sessions consisted of bench press , deadlift , prone row and back squat exercise to failure at an intensity of 60 % 1 repetition maximum . Results indicated that participants completed significantly greater repetitions to failure , irrespective of exercise , in the presence of caffeine ( p=0.0001 ) . Mean±S.D of repetitions to failure was 19.6±3.7 and 18.5±4.1 in caffeine and placebo conditions , respectively . There were no differences in peak heart rate or peak blood lactate values across conditions ( both p > 0.05 ) . RPE was significantly lower in the caffeine compared to the placebo condition ( p=0.03 ) and was significantly higher during lower body exercises compared to upper body exercises irrespective of substance ingested ( p=0.0001 ) . For muscle pain perception , a significant condition by exercise interaction ( p=0.027 ) revealed that muscle pain perception was lower in the caffeine condition , irrespective of exercise . With caffeine , pain perception was significantly higher in the deadlift and back squat compared to the bench press . However , with placebo , pain perception was significantly higher for the deadlift and back squat compared to the prone row only . Therefore , acute caffeine ingestion not only enhances resistance exercise performance to failure but also reduces perception of exertion and muscle pain Abstract This study investigated the effects of two different doses of caffeine on endurance cycle time trial performance in male athletes . Using a r and omised , placebo-controlled , double-blind crossover study design , sixteen well-trained and familiarised male cyclists ( Mean ± s : Age = 32.6 ± 8.3 years ; Body mass = 78.5 ± 6.0 kg ; Height = 180.9 ± 5.5 cm [Vdot]O2peak = 60.4 ± 4.1 ml · kg−1 · min−1 ) completed three experimental trials , following training and dietary st and ardisation . Participants ingested either a placebo , or 3 or 6 mg · kg−1 body mass of caffeine 90 min prior to completing a set amount of work equivalent to 75 % of peak sustainable power output for 60 min . Exercise performance was significantly ( P < 0.05 ) improved with both caffeine treatments as compared to placebo ( 4.2 % with 3 mg · kg−1 body mass and 2.9 % with 6 mg · kg−1 body mass ) . The difference between the two caffeine doses was not statistically significant ( P = 0.24 ) . Caffeine ingestion at either dose result ed in significantly higher heart rate values than the placebo conditions ( P < 0.05 ) , but no statistically significant treatment effects in ratings of perceived exertion ( RPE ) were observed ( P = 0.39 ) . A caffeine dose of 3 mg · kg−1 body mass appears to improve cycling performance in well-trained and familiarised athletes . Doubling the dose to 6 mg · kg−1 body mass does not confer any additional improvements in performance Research ers have long been investigating strategies that can increase athletes ' ability to oxidize fatty acids and spare carbohydrate , thus potentially improving endurance capacity . Green-tea extract ( epigallocatechin-3-gallate ; EGCG ) has been shown to improve endurance capacity in mice . If a green-tea extract can stimulate fat oxidation and as a result spare glycogen stores , then athletes may benefit through improved endurance performance . Eight male cyclists completed a study incorporating a 3-way crossover , r and omized , placebo-controlled , double-blinded , diet-controlled research design . All participants received 3 different treatments ( placebo 270 mg , EGCG 270 mg , and placebo 270 mg + caffeine 3 mg/kg ) over a 6-day period and 1 hr before exercise testing . Each participant completed 3 exercise trials consisting of 60 min of cycling at 60 % maximum oxygen uptake ( VO2(max ) ) immediately followed by a self-paced 40-km cycling time trial . The study found little benefit in consuming green-tea extract on fat oxidation or cycling performance , unlike caffeine , which did benefit cycling performance . The physiological responses observed during submaximal cycling after caffeine ingestion were similar to those reported previously , including an increase in heart rate ( EGCG 147 + /- 17 , caffeine 146 + /- 19 , and placebo 144 + /- 15 beats/min ) , glucose at the 40-min exercise time point ( placebo 5.0 + /- 0.8 , EGCG 5.4 + /- 1.0 , and caffeine 5.8 + /- 1.0 mmol/L ) , and resting plasma free fatty acids and no change in the amount of carbohydrate and fat being oxidized . Therefore , it was concluded that green-tea extract offers no additional benefit to cyclists over and above those achieved by using caffeine Abstract Although caffeine is a widely used ergogenic re source , some information regarding its effects on resistance exercises is still lacking . The objective of the present study was to verify the acute effect of the ingestion of two different doses of caffeine on performance during a session of resistance exercises and to analyze the perception of the subjects in relation to the intake of caffeine . Following a double-blind , r and omised , cross-over , controlled , and non-placebo design , 14 trained and healthy men ( 24.7 ± 6.8 years ; 79.8 ± 9.8 kg ; 177.3 ± 8.5 cm ) performed a training session in chest-press , shoulder-press , and biceps curl exercises ( 3 sets until exhaustion ; 70 % 1RM ; 3 min rest interval ; 2 s for each concentric and eccentric phase ) on three non-consecutive days after ingestion of 3 mg.kg−1 caffeine ( CAF3 ) , 6 mg.kg−1 caffeine ( CAF6 ) , or no substance ( CON ) . Subjects were informed that one of the caffeine doses would be placebo . The total number of repetitions performed in CON ( 93.6 ± 22.4 ) was significantly lower than in CAF3 ( 108.0 ± 19.9 , P = 0.02 ) and in CAF6 ( 109.3 ± 19.8 , P = 0.03 ) and there were no differences between caffeine doses . Eight subjects noticed that caffeine was in CAF3 and six in CAF6 and there were no differences in the number of repetitions between sessions in which the subjects perceived and did not perceive caffeine . In conclusion , caffeine doses of 3 or 6 mg.kg−1 similarly increased performance in resistance upper limb exercises , independent of the subject 's perception of substance ingestion Bertolaccini , AL , da Silva , AA , Teixeira , EL , Schoenfeld , BJ , and de Salles Painelli , V. Does the expectancy on the static stretching effect interfere with strength-endurance performance ? J Strength Cond Res XX(X ) : 000 - 000 , 2019-Static stretching ( SS ) may interfere with strength performance . Such interference , however , may be partially attributed to the subjects ' or research er 's expectancy about the SS effects . We aim ed to examine whether the manipulation of subjects ' expectancy of SS on force production could influence strength-endurance during unilateral knee extension exercise . Eighteen strength-trained men were r and omly divided into positively biased ( PB ; N = 09 ) or negatively biased ( N = 09 ) groups on the possible effects of SS on performance . Subjects ' total number of repetitions and total volume of exercise were assessed during strength-endurance tests ( 4 sets performed to failure at 70 % of 1 repetition maximum ) performed under 2 different conditions on separate days : Control-no stretching ( CON ) ; or SS . Static stretching consisted of 3 sets of 3 stretching exercises , lasting 30 seconds each . Data were analyzed using mixed models . Neither the total number of repetitions nor the total volume was significantly different between the CON and SS conditions , nor for type of bias ( all p > 0.05 ) . However , the number of repetitions in the last set of exercise was greater during SS compared with CON for the PB group ( p = 0.01 ) . Although previous negative or positive information about SS did not interfere with the total number of repetitions and total volume of exercise , previous positive information about SS improved performance in the last set of exercise . Expectancy therefore may have played a partial role influencing strength-endurance in previous studies Abstract The goal of this r and omized , double-blind , cross-over study was to assess the acute effects of caffeine ingestion on muscular strength and power , muscular endurance , rate of perceived exertion ( RPE ) , and pain perception ( PP ) in resistance-trained men . Seventeen volunteers ( mean ± SD : age = 26 ± 6 years , stature = 182 ± 9 cm , body mass = 84 ± 9 kg , resistance training experience = 7 ± 3 years ) consumed placebo or 6 mg kg−1 of anhydrous caffeine 1 h before testing . Muscular power was assessed with seated medicine ball throw and vertical jump exercises , muscular strength with one-repetition maximum ( 1RM ) barbell back squat and bench press exercises , and muscular endurance with repetitions of back squat and bench press exercises ( load corresponding to 60 % of 1RM ) to momentary muscular failure . RPE and PP were assessed immediately after the completion of the back squat and bench press exercises . Compared to placebo , caffeine intake enhanced 1RM back squat performance ( + 2.8 % ; effect size [ ES ] = 0.19 ; p = .016 ) , which was accompanied by a reduced RPE ( + 7 % ; ES = 0.53 ; p = .037 ) , and seated medicine ball throw performance ( + 4.3 % , ES = 0.32 ; p = .009 ) . Improvements in 1RM bench press were not noted although there were significant ( p = .029 ) decreases in PP related to this exercise when participants ingested caffeine . The results point to an acute benefit of caffeine intake in enhancing lower-body strength , likely due to a decrease in RPE ; upper- , but not lower-body power ; and no effects on muscular endurance , in resistance-trained men . Individuals competing in events in which strength and power are important performance-related factors may consider taking 6 mg kg−1 of caffeine pre-training/competition for performance enhancement Background A patient ’s response to treatment may be influenced by the expectations that the patient has before initiating treatment . In the context of clinical trials , the influence of participant expectancy may blur the distinction between real and sham treatments , reducing statistical power to detect specific treatment effects . There is therefore a need for a tool that prospect ively predicts expectancy effects on treatment outcomes across a wide range of treatment modalities . Purpose To help assess expectancy effects , we created the Stanford Expectations of Treatment Scale ( SETS ) : an instrument for measuring positive and negative treatment expectancies . Internal reliability of the instrument was tested in Study 1 . Criterion validity of the instrument ( convergent , discriminant , and predictive ) was assessed in Studies 2 and 3 . Methods The instrument was developed using 200 participants in Study 1 . Reliability and validity assessment s were made with an additional 423 participants in Studies 2 and 3 . Results The final six-item SETS contains two subscales : positive expectancy ( α = 0.81–0.88 ) and negative expectancy ( α = 0.81–0.86 ) . The subscales predict a significant amount of outcome variance ( between 12 % and 18 % ) in patients receiving surgical and pain interventions . The SETS is simple to administer , score , and interpret . Conclusion The SETS may be used in clinical trials to improve statistical sensitivity for detecting treatment differences or in clinical setting s to identify patients with poor treatment expectancies |
1,619 | 27,518,547 | Subgroup analyses revealed that the prevalence and severity of depression are greatest in primary Sjogren ’s syndrome patients .
Conclusion Depression and anxiety are more prevalent in DED patients than in controls .
Among patients with DED , those suffering from primary Sjogren 's syndrome have higher prevalence and severity of depression | Aim To evaluate the association of dry eye disease ( DED ) with depression and anxiety . | Aim To investigate the association between dry eye symptoms and depression in an adult population . Methods In this population -based cross-sectional study , a r and om sample of 1957 subjects from the Beijing Eye Study was examined for dry eye disease ( DED ) in 2006 . All patients completed an interviewer-assisted question naire on dry eye symptoms and underwent measurement of tear break-up time ( TBUT ) , slit-lamp evaluation of corneal staining and meibomian gl and dysfunction ( MGD ) , and the Schirmer test . In 2011 , 1456 subjects from this sample were evaluated for depression using a depression scale . The association between depression symptoms and dry eye clinical tests was evaluated . Results Definite depression was more prevalent in patients with DED than in subjects without DED ( 13.7±0.4 % vs 8.6±0.3 % , p=0.02 ) . The depression score was correlated with dry eye symptoms ( correlation coefficient r=0.07 ; p=0.013 ) but not with TBUT ( p=0.18 ) , the Schirmer test ( p=0.37 ) , corneal staining ( p=0.30 ) and MGD evaluation ( p=0.93 ) . In multivariate regression analysis , the risk of definite depression remained significantly associated with dry eye symptoms ( p=0.028 ) after adjusting for lower cognitive status ( p=0.01 ) , rural region of habitation ( p=0.023 ) and lower body weight ( p=0.05 ) . Conclusions In an older population from Beijing , depression was associated with DED and in particular with dry eye symptoms OBJECTIVE To investigate the significant determinants of health-related quality of life ( HRQOL ) and the association of the EULAR Sjögren 's syndrome patient reported index ( ESSPRI ) with clinical parameters including HRQOL in Korean patients with primary Sjögren 's syndrome ( pSS ) compared with non-SS sicca patients . METHODS We prospect ively analysed 104 pSS and 42 non-SS sicca patients . Clinical data including Short Form 36 ( SF-36 ) scores , self- assessment s for symptoms and ESSPRI were cross-sectionally collected . RESULTS Although most self- assessment s and HRQOL statuses were comparable , different association patterns between HRQOL and symptoms were observed in pSS and non-SS sicca patients . pSS patients with low HRQOL had significantly higher ESSPRI scores [ P = 7.6 × 10(-6 ) for physical component summary ( PCS ) subgroups and P = 0.0015 for mental component summary ( MCS ) subgroups ] and ESSPRI scores showed a significant association with all SF-36 scales in pSS patients ( all P ≤ 0.0020 ) . Moreover , in multivariate linear regression analyses , ESSPRI ( P = 0.035 ) and depression ( P = 4.1 × 10(-14 ) ) were significantly correlated with the PCS and the MCS , respectively . However , in the non-SS sicca group , xerostomia inventory ( XI ) scores were higher in the low PCS subgroup ( P = 0.031 ) and this correlated with five SF-36 scales ( all P ≤ 0.046 ) . XI scores ( P = 0.0039 ) and anxiety ( P = 7.9 × 10(-10 ) ) were the main determinants of the PCS and MCS , respectively . CONCLUSION HRQOL levels were differentially associated with clinical facets in pSS and non-SS sicca patients , although the groups had similar clinical symptoms and HRQOL reduction . Because depression and ESSPRI are major determinants of HRQOL in Korean pSS patients , ESSPRI is suggested to be disease-specific for pSS Objective . Although multiple diseases associated with primary Sjögren ’s syndrome ( pSS ) have been reported , reliable data regarding the prevalence of specific medical comorbidities among patients with pSS remain sparse . We investigated the prevalence and risk for a broad spectrum of medical conditions among patients with pSS in Taiwan . Methods . A total of 1974 patients with pSS were eligible for inclusion in the study group . We r and omly selected 9870 enrollees matched with the study subjects , using the Taiwan National Health Insurance Research Data set for 2006 and 2007 , inclusive . Conditional logistic regression analyses conditioned on sex , age , monthly income , and level of urbanization of the patient ’s community were used to calculate the odds ratios ( OR ) of various comorbid conditions . Results . Pearson chi-square tests revealed that patients with pSS had significantly higher prevalence of hyperlipidemia , cardiac arrhythmias , headaches , migraines , fibromyalgia ( FM ) , asthma , pulmonary circulation disorders , hypothyroidism , liver disease , peptic ulcers , hepatitis B , deficiency anemias , depression , and psychoses . Conditional regression analyses showed that , compared to patients without the condition , patients with pSS were more likely to have hyperlipidemia ( OR 1.42 ) , cardiac arrhythmias ( OR 1.32 ) , headaches ( OR 1.47 ) , migraines ( OR 1.86 ) , FM ( OR 1.71 ) , asthma ( OR 1.54 ) , pulmonary circulation disorders ( OR 1.42 ) , hypothyroidism ( OR 2.37 ) , liver disease ( OR 1.89 ) , peptic ulcers ( OR 1.88 ) , hepatitis B ( OR 2.34 ) , deficiency anemias ( OR 1.33 ) , depression ( OR 2.57 ) , and psychoses ( OR 2.15 ) . Conclusion . The prevalence of several comorbidities was increased among the patients with pSS . Our study provides epidemiological data for comorbidities among pSS patients in an ethnic Chinese population OBJECTIVE Corneal and ocular wavefront aberrations were recorded together with clinical examination results and patient-reported vision-related quality -of-life evaluation results to define the relevance of dynamic optical analysis of the eye in dry eye disease ( DED ) . DESIGN Prospect i ve and comparative clinical study . PARTICIPANTS Forty DED patients and 40 age- and gender-matched control subjects . METHODS Serial measurements of ocular and corneal higher-order aberrations ( HOAs ) after blink were performed for 10 seconds using the KR-1 aberrometer ( Topcon , Clichy , France ) . Vision-related health-targeted quality of life was evaluated using the Ocular Surface Disease Index ( OSDI ) question naire . The clinical examination included tear film assessment ( tear film break-up time and Schirmer I test ) , ocular surface damage assessment with the Oxford and van Bijsterveld indexes , and Meibomian dysfunction grading . Tear osmolarity also was measured . MAIN OUTCOME MEASURES The time course of HOAs and modulation transfer function ( MTF ) was compared between groups and was analyzed in comparison with the OSDI and clinical data in DED patients . RESULTS The root mean square of ocular and corneal total HOAs , particularly third-order aberrations , significantly increased over the 10-second period in DED patients , whereas no change occurred in controls . Analysis of MTF revealed progressive degradation of ocular optical quality result ing from loss of contrast at intermediate and high spatial frequencies in DED patients compared with controls . The progression index for corneal HOAs was correlated with the subjective index of patient-reported visual outcomes and with objective clinical findings of tear film and ocular surface damage . CONCLUSIONS Objective measurement of the time course of HOAs may constitute a new single instrument to evaluate and manage patients with DED because it reliably reflects the completeness of the disease PURPOSE A population -based cross-sectional study to investigate the association between depression and dry eye disease ( DED ) in a community-dwelling elderly population . METHODS The subjects were 657 Korean elders ≥ 65 years of age r and omly selected from an official household registration data base in Yongin , Korea . DED symptoms were assessed using the six-item Dry Eye Question naire . DED signs were evaluated using the Schirmer test , fluorescein stain score , tear film break-up time ( BUT ) . Depression was assessed using the Korean version of the Short Geriatric Depression Scale ( SGDS-K ) . The association between DED and depression was evaluated using logistic linear analyses . RESULTS The SGDS-K score correlated with the number of positive responses in the Dry Eye Question naire ( r = 0.229 , P < 0.001 ) , but not with tear film break-up time ( r = 0.041 , P = 0.139 ) or Schirmer test score ( r = 0.048 , P = 0.642 ) . In the binary logistic regression model , female sex ( P = 0.014 ) , residence in urban areas ( P < 0.001 ) , depression ( P < 0.001 ) , and Schirmer score of ≤ 5 mm ( P = 0.035 ) were associated with the risk of DED . Depression was associated with the risk of DED ( P < 0.001 ) in the patients with Schirmer score > 5 mm but not in those with Schirmer score ≤ 5 mm ( P = 0.290 ) . CONCLUSIONS Depression was associated with DED symptoms in subjects with normal or mildly reduced tear production OBJECTIVE To compare pain , fatigue , and sicca symptoms ; quality of life ; and psychological status between patients with primary Sjögren 's syndrome ( SS ) and those with sicca symptoms but no autoimmune features ( sicca asthenia polyalgia syndrome [ SAPS ] ) , and to determine whether a psychological pattern can be detected in patients with SAPS , which could suggest psychological distress as the cause . METHODS This cross-sectional , prospect i ve study included 111 patients with primary SS according to the American-European Consensus Group criteria and 65 SAPS patients with no focus on lip biopsy and no anti-SSA/SSB antibodies . Pain , fatigue , and sicca symptoms were assessed using visual analog scales ; quality of life was assessed using the Short Form 36 ( SF-36 ) ; and psychological distress by the Symptom Checklist-90-Revised ( SCL-90-R ) question naire . RESULTS No difference was observed between primary SS and SAPS patients for pain , fatigue , sicca symptoms , quality of life , and psychological status . Fatigue and pain , but not dryness , were correlated with both quality of life and psychological distress in both groups . For primary SS patients , physical and mental composite scores on the SF-36 correlated well with global severity index ( GSI ) scores of the SCL-90-R ( r = -0.29 , P = 0.006 and r = -0.61 , P < 0.0001 , respectively ) . CONCLUSION Patients with primary SS and SAPS do not differ in quality of life or psychological status . Although both diseases probably have a different origin , they may require the same psychological support or psychiatric care . The strong correlation between the composite physical and mental scores of the SF-36 and the GSI scores of the SCL-90-R in primary SS patients emphasizes the importance of the psychological dimension in results of the SF-36 |
1,620 | 22,248,019 | Overall , published studies report positive correlations between multiple EC-derived molecules and the diagnosis of sepsis , supporting the critical role of EC activation in sepsis .
Conclusions Multiple endothelial-derived molecules are positively correlated with the presence of sepsis in humans , and variably correlated to other clinical ly-important outcomes . | Introduction A strong biologic rationale exists for targeting markers of endothelial cell ( EC ) activation as clinical ly informative biomarkers to improve diagnosis , prognostic evaluation or risk-stratification of patients with sepsis .
Methods The objective was to review the literature on the use of markers of EC activation as prognostic biomarkers in sepsis . | In this prospect i ve study of 45 patients , we tested the hypothesis that markedly elevated levels of plasma von Willebr and antigen ( vWf-Ag ) a marker of endothelial cell injury , might predict the development of acute lung injury in patients with nonpulmonary sepsis syndrome . Acute lung injury was quantified on a four-point scoring system . At the time of entry into the study , none of the 45 patients had evidence of lung injury . Subsequently , 15 patients developed lung injury and 30 patients did not develop lung injury . The mean plasma vWf-Ag level was markedly elevated in the 15 patients who developed lung injury compared with the 30 patients who did not develop lung injury ( 588 + /- 204 vs. 338 + /- 196 , percentage of control , P less than 0.01 ) . Furthermore , a plasma vWf-Ag level greater than or equal to 450 was 87 % sensitive and 77 % specific for predicting the development of acute lung injury in the setting of nonpulmonary sepsis . In addition , the combination of a plasma vWf-Ag greater than 450 and nonpulmonary organ failure at the time of entry into the study had a positive predictive value of 80 % for acute lung injury . Also , a plasma vWf-Ag level greater than 450 had a positive predictive value of 80 % for identifying nonsurvivors . Thus , in patients with nonpulmonary sepsis , an elevated level of plasma vWf-Ag is a useful , early biochemical marker of endothelial injury and it has both predictive and prognostic value Introduction The endothelial specific angiopoietin (Ang)-Tie2 lig and -receptor system has been identified as a non-redundant mediator of endothelial activation in experimental sepsis . Binding of circulating Ang-1 to the Tie2 receptor protects the vasculature from inflammation and leakage , whereas binding of Ang-2 antagonises Tie2 signalling and disrupts endothelial barrier function . Here , we examine whether circulating Ang-1 and /or Ang-2 independently predict mortality in a cohort of critically ill medical patients . Methods Circulating vascular endothelial growth factor ( VEGF ) , Ang-1 and Ang-2 were prospect ively measured in sera from 29 healthy controls and 43 medical ICU patients by immunoradiometric assay ( IRMA ) and ELISA , respectively . Survival after 30 days was the primary outcome studied . Results Median serum Ang-2 concentrations were increasingly higher across the following groups : healthy controls , patients without sepsis , patients with sepsis and patients with septic shock . In contrast , Ang-1 and VEGF concentrations were significantly lower in all patient groups compared with healthy controls . Ang-2 correlated with partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen ( FiO2 ) , tissue hypoxia , Sequential Organ Failure Assessment ( SOFA ) and Physiology and Chronic Health Evaluation II ( APACHE II ) score . Multivariate Cox regression analyses confirmed a strong independent prognostic impact of high Ang-2 as a novel marker of 30-day survival . Conclusions A marked imbalance of the Ang-Tie system in favour of Ang-2 is present in critically ill medical patients . Our findings highlight the independent prognostic impact of circulating Ang-2 in critical illness . Ang-2 may be used as a readily available powerful predictor of outcome and may open new perspectives to individualise treatment in the ICU Abstract Angiogenesis is a key component of the repair mechanisms triggered by tissue injury . Vascular endothelial growth factor ( VEGF ) is an important mediator of angiogenesis , as it acts directly and specifically on endothelial cells . VEGF produced locally in regenerating tissue may spill over into the systemic circulation , and measuring levels of circulating VEGF may allow monitoring of angiogenesis . To determine whether circulating VEGF is increased after severe injury , we measured concentrations of VEGF in serial serum sample s of 23 mechanical burn patients , 55 patients with multiple trauma and 56 healthy normal controls , using a newly established ELISA assay . In burn patients , serum VEGF was increased on day 1 ( 369.4 ± 88.0 pg/ml ) and on day 3 ( 452.0 ± 65.3 pg/ml ) , reached highest levels on day 14 ( 1809.5 ± 239.7 pg/ml ) and was still elevated on day 21 post-burn ( 1339.8 ± 208.7 pg/ml ) ( mean ± SEM , p<0.01 ) , when compared with healthy controls ( 82.2 ± 10.8 pg/ml ( mean ± SEM ) ) . Likewise , in trauma patients , serum VEGF showed a trend towards elevated values on the day of admission ( 186.9 ± 43.9 pg/ml ) and on day 3 after injury ( 193.2 ± 62.1 pg/ml ) . Thereafter , serum VEGF increased further ( day 7 , 507.0 ± 114.7 pg/ml ) , peaked on day 14 ( 742.4 ± 151.8 pg/ml ) and was still elevated on day 21 after injury ( 693.1 ± 218.6 pg/ml ( mean ± SEM , p<0.01 ) ) . No significant correlation was observed between peak serum VEGF and initial severity of mechanical ( Injury Severity Score ) or burn injury ( percentage of body surface burned ) . However , in both burn and trauma patients , the subgroup of patients with uncomplicated healing showed significantly higher increases of serum VEGF than the subgroup who developed severe complications during the post-traumatic course , such as sepsis , adult respiratory distress syndrome or multiple organ failure ( p<0.05 ) . Thus , markedly enhanced levels of serum VEGF are present one to three weeks after trauma or burn injury . Further , occurrence of severe complications during the post-traumatic period is associated with lesser increases of serum VEGF Objective : To measure plasma levels of angiopoietin-1 ( Ang-1 ) , angiopoietin-2 ( Ang-2 ) , and vascular endothelial growth factor ( VEGF ) early after trauma and to determine their clinical significance . Background : Angiopoietins and VEGF play a central role in the physiology and pathophysiology of endothelial cells . Ang-2 has recently been shown to have pathogenetic significance in sepsis and acute lung injury . Little is known about the role of angiopoietins and VEGF early after trauma . Methods : Blood specimens from consecutive major trauma patients were obtained immediately upon arrival in the emergency department and plasma sample s assayed for Ang-1 , Ang-2 , VEGF , markers of endothelial activation , protein C pathway , fibrinolytic system , and complement . Base deficit was used as a measure of tissue hypoperfusion . Data were collected prospect ively . Results : Blood sample s were obtained from 208 adult trauma patients within 30 minutes after injury before any significant fluid resuscitation . Plasma levels of Ang-2 , but not Ang-1 and VEGF were increased and correlated independently with severity of injury and tissue hypoperfusion . Furthermore , plasma levels of Ang-2 correlated with markers of endothelial activation , coagulation abnormalities , and activation of the complement cascade and were associated with worse clinical outcome . Conclusions : Ang-2 is released early after trauma with the degree proportional to both injury severity and systemic hypoperfusion . High levels of Ang-2 were associated with an activated endothelium , coagulation abnormalities , complement activation , and worse clinical outcome . These data indicate that Ang-2 is a marker and possibly a direct mediator of endothelial activation and dysfunction after severe trauma Introduction Previous reports suggest that endothelial activation is an important process in sepsis pathogenesis . We investigated the association between biomarkers of endothelial cell activation and sepsis severity , organ dysfunction sequential organ failure assessment ( SOFA ) score , and death . Methods This is a prospect i ve , observational study including adult patients ( age 18 years or older ) presenting with clinical suspicion of infection to the emergency department ( ED ) of an urban , academic medical center between February 2005 and November 2008 . Blood was sample d during the ED visit and biomarkers of endothelial cell activation , namely soluble fms-like tyrosine kinase-1 ( sFlt-1 ) , plasminogen activator inhibitors -1 ( PAI-1 ) , sE-selectin , soluble intercellular adhesion molecule ( sICAM-1 ) , and soluble vascular cell adhesion molecule ( sVCAM-1 ) , were assayed . The association between biomarkers and the outcomes of sepsis severity , organ dysfunction , and in-hospital mortality were analyzed . Results A total of 221 patients were included : sepsis without organ dysfunction was present in 32 % , severe sepsis without shock in 30 % , septic shock in 32 % , and 6 % were non-infected control ED patients . There was a relationship between all target biomarkers ( sFlt-1 , PAI-1 , sE-selectin , sICAM-1 , and sVCAM-1 ) and sepsis severity , P < 0.05 . We found a significant inter-correlation between all biomarkers , including the strongest correlations between sFlt-1 and sE-selectin ( r = 0.55 , P < 0.001 ) , and between sFlt-1 and PAI-1 ( 0.56 , P < 0.001 ) . Among the endothelial cell activation biomarkers , sFlt-1 had the strongest association with SOFA score ( r = 0.66 , P < 0.001 ) , the highest area under the receiver operator characteristic curve for severe sepsis of 0.82 , and for mortality of 0.91 . Conclusions Markers of endothelial cell activation are associated with sepsis severity , organ dysfunction and mortality . An improved underst and ing of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis OBJECTIVE Soluble adhesion molecules are regarded to be markers of inflammation , endothelial activation , or damage . The influence of age on plasma concentrations of circulating adhesion molecules should be serially studied in critically ill intensive care patients . DESIGN Prospect i ve and descriptive study over 5 days . SETTING Clinical investigation in a surgical intensive care unit of a university hospital . PATIENTS Thirty critically ill patients ( Acute Physiology and Chronic Health Evaluation [ APACHE ] II score of > 15 points ) , with sepsis secondary to postoperative complications , were included in this study . Fifteen consecutive patients aged < 50 yrs and 15 consecutive patients aged > 70 yrs were prospect ively studied . INTERVENTIONS All patients were treated by the st and ard protocol s of our intensive care unit , which did not differ between the groups . The patients received continuous analgesia-sedation and mechanical ventilation . Intensivists caring for the patients were not involved in the study and were blinded to data analysis . MEASUREMENTS AND MAIN RESULTS Hemodynamic parameters were extensively monitored in all patients . From arterial blood sample s , plasma concentrations of soluble adhesion molecules ( endothelial leukocyte adhesion molecule-1 , intercellular adhesion molecule-1 , vascular cell adhesion molecule-1 , granule membrane protein-140 ) were measured on the day of admission ( i.e. , baseline values ) and during the following 5 days . Three of the younger patients and six of the elderly patients died during the study period ( p < .05 ) . Oxygen delivery and consumption , and the other hemodynamic data , were without group differences throughout the study . Plasma concentrations of all adhesion molecules were beyond normal at baseline in both groups . These concentrations increased further during the first 2 to 3 days in both groups , with a significantly higher increase in the elderly patients ( endothelial leukocyte adhesion molecule-1 to 179 + /- 32 ng/mL ; intercellular adhesion molecule-1 to 1695 + /- 158 ng/mL ; vascular cell adhesion molecule-1 to 1395 + /- 212 ng/mL ; and granule membrane protein-140 to 888 + /- 119 ng/mL ) . In the younger patients , concentrations of soluble adhesion molecules decreased later in the study and almost reached baseline values on day 5 . In the elderly patients , these concentrations remained significantly higher until the end of the study . CONCLUSIONS The higher plasma concentrations of the measured adhesion molecules in elderly critically ill patients indicate that elderly patients are more prone than younger patients to a more pronounced activation or even damage of the endothelium . Further work needs to be done to determine the prognostic importance and to define the role of soluble adhesion molecules , particularly in the elderly critically ill patient ObjectiveS epsis and systemic inflammatory response syndrome ( SIRS ) result in the release in plasma of inflammatory cytokines and soluble forms of adhesion molecules in relation to endothelial activation . This study was design ed to compare cerebrospinal fluid ( CSF ) concentrations of adhesion molecules in meningitis and SIRS without neurological infection and to evaluate in meningitis whether they originate from passive diffusion through damaged blood – CSF barrier or from local production . Design Prospect i ve observational study . Setting University hospital medical intensive care unit . Patients Nineteen patients with meningitis and 41 patients with sepsis or SIRS without cerebrospinal infection consecutively admitted to the critical care unit over an 18-month period . Interventions Soluble forms of adhesion molecules ( ICAM-1 , VCAM-1 , E-selectin ) and cytokines ( interleukin (IL)-1β and TNF−α ) were measured in paired CSF and blood sample s. Results Serum concentrations of soluble adhesion molecules and cytokines were increased in the two groups , without significant differences . The CSF concentrations were elevated in both cases , whereas patients with meningitis demonstrated significantly higher CSF concentrations of soluble ICAM-1 , VCAM-1 , E-selectin , and TNF-α ( p<0.001 ) , with higher corresponding CSF/serum ratios . Correlations between CSF and serum concentrations were found only in meningitis . These correlations were strong for soluble ICAM-1 ( r2=0.7 , p<0.001 ) and E-selectin ( r2=0.9 , p<0.001 ) , but weaker for VCAM-1 . VCAM-1 CSF/serum ratios were increased , in comparison with ICAM-1 and E-selectin CSF/serum ratios , despite similar molecular weights . Serum and CSF levels of cytokines and adhesion molecules were not predictive of death for the whole population , except concentrations of ICAM-1 significantly increased in non-surviving patients ( p<0.05 ) . Conclusions The CSF soluble adhesion molecules are increased in sepsis , SIRS and meningitis . In meningitis , the correlation between CSF and serum concentrations of adhesion molecules and the presence of a discrepancy of CSF/serum ratios for molecules of the same molecular weight may suggest intrathecal shedding in addition to diffusion through blood – CSF barrier The findings of this study suggest that systemic inflammation results in ADAMTS13 deficiency , and thereby activates hemostasis . In a prospect i ve , longitudinal study , we investigated the association between decreased ADAMTS13 activity and impaired hemostasis , as well as organ dysfunctions in patients with systemic inflammation due to extracorporeal cardiopulmonary circuit or with severe sepsis . Similar to negative acute phase proteins , ADAMTS13 activity declined stepwise according to the extent of inflammatory responses . A marked imbalance between ADAMTS13 activity and VWF antigen level was associated with the appearance of ultra-large VWF multimers in plasma , with organ dysfunction and lethality . Our data support the view that systemic inflammation results in an ADAMTS13 deficiency which activates hemostasis Introduction Despite recent advances in the management of septic shock , mortality rates are still unacceptably high . Early identification of the high-mortality risk group for early intervention remains an issue under exploration . Vascular endothelial growth factor ( VEGF ) , soluble vascular endothelial growth factor receptor-1 ( sVEGFR1 ) and urokinase plasminogen activator ( uPA ) have diverse effects in the pathogenesis of sepsis , which involve pro-inflammation , anti-inflammation , endothelial cell repair , and vascular permeability change . Their roles in predicting mortality and organ dysfunction remain to be clarified . Methods Pneumonia-related septic shock patients from medical intensive care units were enrolled for this prospect i ve observational study . We also included 20 patients with pneumonia without organ dysfunction for comparison . Plasma levels of VEGF and sVEGFR1 and uPA activity within 24 hours of shock onset were measured . We compared plasma levels of these biomarkers with APACHE II scores between subgroups of patients , and evaluated their predictive value for 28-day mortality and organ dysfunction . Results A total of 101 patients , including 81 with pneumonia-related septic shock and 20 with pneumonia without organ dysfunction , were enrolled . Non-survivors of septic shock had significantly higher plasma sVEGFR1 levels ( 659.3 ± 1022.8 vs. 221.1 ± 268.9 pg/mL , respectively , P < 0.001 ) and uPA activity ( 47.2 ± 40.6 vs. 27.6 ± 17.2 units , respectively , P = 0.001 ) when compared with those of the survivors . Kaplan-Meier survival analysis demonstrated significantly higher mortality in patients with higher levels of sVEGFR1 ( P < 0.001 ) and uPA activity ( P = 0.031 ) . In Cox regression analysis , plasma sVEGFR1 level was independently associated with , and best predicted , the 28-day mortality of septic shock ( HR : 1.55 , 95 % CI : 1.05 - 2.30 ) . Plasma sVEGFR1 level and uPA activity had good correlation with renal dysfunction , metabolic acidosis , and hematologic dysfunction ; their levels significantly increased when the number of organ dysfunctions increased . In multivariate analysis , plasma sVEGFR1 level ( HR : 2.82 , 95 % CI : 1.17 - 6.81 ) and uPA activity ( HR : 2.75 , 95 % CI : 1.06 - 7.13 ) were independent predictors of the presence of concomitant multi-organ dysfunction . The predictive value of VEGF for mortality and organ dysfunction was limited in pneumonia-related septic shock patients . Conclusions High plasma sVEGFR1 level in the early stage of pneumonia-related septic shock independently predicted 28-day mortality and multi-organ dysfunction Background Several biological markers of lung injury are predictors of morbidity and mortality in patients with acute lung injury ( ALI ) . The low tidal volume lung-protective ventilation strategy is associated with a significant decrease in plasma biomarker levels compared to the high tidal volume ventilation strategy . The primary objective of this study was to test whether the institution of lung-protective positive pressure ventilation in spontaneously ventilating patients with ALI exacerbates pre-existing lung injury by using measurements of biomarkers of lung injury before and after intubation . Material s and methods A prospect i ve observational cohort study was conducted in the intensive care unit of a tertiary care university hospital . Twenty-five intubated , mechanically ventilated patients with ALI were enrolled . Physiologic data and serum sample s were collected within 6 hours before intubation and at two different time points within the first 24 hours after intubation to measure the concentration of interleukin (IL)-6 , IL-8 , intercellular adhesion molecule 1 ( ICAM-1 ) , and von Willebr and factor ( vWF ) . The differences in biomarker levels before and after intubation were analysed using repeated measures analysis of variance and a paired t test with correction for multiple comparisons . Results Before endotracheal intubation , all of the biological markers ( IL-8 , IL-6 , ICAM-1 , and vWF ) were elevated in the spontaneously breathing patients with ALI . After intubation and the institution of positive pressure ventilation ( tidal volume 7 to 8 ml/kg per ideal body weight ) , none of the biological markers was significantly increased at either an early ( 3 ± 2 hours ) or later ( 21 ± 5 hours ) time point . However , the levels of IL-8 were significantly decreased at the later time point ( 21 ± 5 hours ) after intubation . During the 24-hour period after intubation , the PaO2/FiO2 ( partial pressure of arterial oxygen/fraction of the inspired oxygen ) ratio significantly increased and the plateau airway pressure significantly decreased . Conclusion Levels of IL-8 , IL-6 , vWF , and ICAM-1 are elevated in spontaneously ventilating patients with ALI prior to endotracheal intubation . The institution of a lung-protective ventilation strategy with positive pressure ventilation does not further increase the levels of biological markers of lung injury . The results suggest that the institution of a lung-protective positive pressure ventilation strategy does not worsen the pre-existing lung injury in most patients with ALI AIM The aim of this study was to investigate whether the plasma levels of the circulating adhesion molecules sICAM-1 and sE-selectin could serve as early predictors of developing sepsis and its severity . METHODS Twenty-four patients admitted to an intensive care unit with a high risk of developing septic complications were enrolled in this study . Patients were divided into three groups : group I , with infection without systemic sepsis , n = 8 ; group II , surviving patients with severe sepsis and multi-organ failure ( MOF ) , n = 8 ; and group III , nonsurviving patients with severe sepsis and MOF , n = 8 . Classification of patients was performed according to the clinical criteria defined by the Sepsis Consensus Conference in 1992 . Blood sample s were taken at 7 a.m. starting from the day of admission until the 7th day after diagnosis of sepsis . Plasma levels of sICAM-1 and sE-selectin were determined in all sample s taken between the 3rd pre-septic day and the 7th day after the diagnosis of sepsis was made . RESULTS In group I , both sICAM-1 ( 354.21 + /- 128.60 ng/ml , 86 sample s ) and sE-selectin ( 30.41 + /- 7.20 ng/ml , 86 sample s ) levels remained within the reference range over the whole period of observation . The sICAM-1 levels of group II ( between 550.82 + /- 275.67 ng/ml and 445.08 + /- 243.63 ng/ml ) tended to show values above the reference range without being significant . Mean sICAM-1 levels in group II did not differ from those of group I. From the 2nd pre-septic day onwards the sICAM-1 levels of group III increased , but not significantly . Significant differences in sICAM-1 levels between group I and group III were observed , with peaks at the sample s of the 2nd preseptic day and after the 3rd day of sepsis , respectively ( P < 0.05 ) . The sE-selectin levels in group II were elevated from the 3rd preseptic day onwards , with a peak value on the 2nd day of sepsis ( P < 0.05 ) . Afterwards , levels decreased to initial values despite ongoing sepsis . Mean values of sE-selectin levels of group I and II were significantly different with the onset of sepsis ( P < 0.05 ) . Plasma levels of sE-selectin in group III were significantly elevated ( 66.30 + /- 9.00 ng/ml on the 3rd pre-septic day ) , reaching their maximal values of 106.67 + /- 21.66 ng/ml at the end of the observation period . Significant differences between sE-selectin levels of groups I and III existed from the 3rd pre-septic day onwards , and between group II and III on the 7th and 8th day of sepsis . CONCLUSION Our results show that sICAM-1 is a relatively non-specific indicator for sepsis . In contrast , sE-selectin seems to be a good and early predictor of the beginning of severe sepsis with MOF . Furthermore , sE-selectin levels seem to have a prognostic value for the severity , possible course , and outcome of developing sepsis The vascular growth factor angiopoietin 2 ( Ang-2 ) is known to promote inflammation and endothelial dysfunction , but its prognostic capacity and relationship to outcomes in human sepsis are unknown . This is a prospect i ve observational cohort study of 66 patients newly admitted to a tertiary care medical intensive care unit ( ICU ) , which included ICU patients with no sepsis ( n = 20 ) as well as those with sepsis ( n = 10 ) , severe sepsis ( n = 12 ) , and septic shock ( n = 24 ) . Clinical data were collected until hospital discharge , and Ang-2 and IL-6 levels were determined on specimens obtained after ICU admission . Serum Ang-2 correlated with IL-6 and severity-of-illness scores . In the septic cohort , circulating Ang-2 levels were significantly higher ( P = 0.01 ) in those who died ( 24.9 ng/mL ; interquartile range , 21.5 - 38.0 ng/mL ) compared with those who survived ( 13.5 ng/mL ; interquartile range , 8.1 - 21.6 ng/mL ) . Elevated circulating serum Ang-2 levels are associated with increased hospital mortality in patients with sepsis Objective To determine the incidence , cost , and outcome of severe sepsis in the United States . Design Observational cohort study . Setting All nonfederal hospitals ( n = 847 ) in seven U.S. states . Patients All patients ( n = 192,980 ) meeting criteria for severe sepsis based on the International Classification of Diseases , Ninth Revision , Clinical Modification . Interventions None . Measurements and Main Results We linked all 1995 state hospital discharge records ( n = 6,621,559 ) from seven large states with population and hospital data from the U.S. Census , the Centers for Disease Control , the Health Care Financing Administration , and the American Hospital Association . We defined severe sepsis as documented infection and acute organ dysfunction using criteria based on the International Classification of Diseases , Ninth Revision , Clinical Modification . We vali date d these criteria against prospect i ve clinical and physiologic criteria in a subset of five hospitals . We generated national age- and gender-adjusted estimates of incidence , cost , and outcome . We identified 192,980 cases , yielding national estimates of 751,000 cases ( 3.0 cases per 1,000 population and 2.26 cases per 100 hospital discharges ) , of whom 383,000 ( 51.1 % ) received intensive care and an additional 130,000 ( 17.3 % ) were ventilated in an intermediate care unit or cared for in a coronary care unit . Incidence increased > 100-fold with age ( 0.2/1,000 in children to 26.2/1,000 in those > 85 yrs old ) . Mortality was 28.6 % , or 215,000 deaths nationally , and also increased with age , from 10 % in children to 38.4 % in those > 85 yrs old . Women had lower age-specific incidence and mortality , but the difference in mortality was explained by differences in underlying disease and the site of infection . The average costs per case were $ 22,100 , with annual total costs of $ 16.7 billion nationally . Costs were higher in infants , nonsurvivors , intensive care unit patients , surgical patients , and patients with more organ failure . The incidence was projected to increase by 1.5 % per annum . Conclusions Severe sepsis is a common , expensive , and frequently fatal condition , with as many deaths annually as those from acute myocardial infa rct ion . It is especially common in the elderly and is likely to increase substantially as the U.S. population ages Objective To investigate the relationship between the soluble derivatives of endothelial adhesion molecules liberated by activated vascular endothelium and the development of the systemic inflammatory response syndrome and organ dysfunction in septic patients . Design Prospect i ve cohort study with controls . Setting University hospital intensive care unit . Patients Healthy volunteers ( controls , n = 85 ) , patients with the systemic inflammatory response syndrome ( n = 21 ) , patients with systemic inflammatory response syndrome and organ dysfunction ( n = 14 ) , and miscellaneous , severely ill patients ( n = 5 ) . Interventions Plasma sample s were collected from consecutive patients who satisfied the criteria for inclusion in the groups listed above . Measurements and Main Results The plasma was assayed by enzyme-linked immunosorbent assay ( ELISA ) for each of the three soluble adhesion molecules : sE-selectin , vascular cell adhesion molecule-1 , and intercellular adhesion molecule-1 . There were low basal amounts of these adhesion molecules in the healthy volunteers , while plasma concentrations of all three adhesion molecules were increased in the sepsis groups . The median soluble E-selectin concentration was higher in those patients with organ dysfunction compared with the concentrations in patients with uncomplicated sepsis ( p < .01 at first and p < .001 when comparing peak values attained ) . No patient survived when the amount of soluble E-selectin was > 30 units/mL. Conclusions Concentrations of circulating vascular endothelial adhesion molecules , especially soluble E-selectin , are increased in patients with systemic inflammatory response syndrome and these concentrations are more increased in patients with organ dysfunction . High plasma concentrations of soluble E-selectin were closely associated with multiple-organ dysfunction and death . Measurement of adhesion molecules , especially soluble E-selectin , might be used to advantage in the management of patients with sepsis . ( Crit Care Med 1994 ; 22:651–657 OBJECTIVE To explore the effects of fluid resuscitation on adhesion molecule and hemodynamics in patients with severe sepsis . METHODS Thirty-eight patients with severe sepsis were r and omly divided into 2 groups : rapid fluid resuscitation group and general treatment group . Before and after fluid resuscitation , heart rate ( HR ) , mean arterial pressure ( MAP ) , central venous pressure ( CVP ) , lactic acid content , plasma P- selection and intercellular adhesion molecule-1 ( ICAM-1 ) contents were determined . RESULTS There were no statistically significant differences in sex , age , resuscitation time and acute physiology and chronic health evaluation II ( APACHE II ) score between the two groups . Compared with general treatment group , more liquid volume but less aramine dosage were used ( both P<0.05 ) , MAP and CVP were increased after fluid resuscitation in rapid fluid resuscitation group ( all P<0.05 ) . The expression of P- selection , HR , contents of ICAM-1 and lactic acid were decreased ( all P<0.05 ) , and all of those were better than those of before fluid resuscitation . CONCLUSION Early rapid fluid resuscitation can improve hemodynamics and decrease the expression of adhesion molecule to retard the development of sepsis This study investigated the relationship of the hepatosplanchnic production and uptake of inflammatory mediators , hepatosplanchnic perfusion , and outcome during major abdominal surgery to evaluate the hypothesis that regional production of inflammatory mediators precedes the development of hepatic dysfunction . This retrospective analysis of data and blood sample s collected during a r and omized controlled clinical trial included high-risk surgical patients undergoing major abdominal surgery in a 24-bed university-afilliated intensive care unit . Patients were divided into a subgroup that developed hepatic dysfunction ( HD+ ) postoperatively and a subgroup without hepatic dysfunction ( HD− ) . Hepatic vein and arterial plasma levels of IL-6 , IL-8 , s-E-selectin , s-ICAM-1 , and the TNF-receptors 55 and 75 were measured , and the flux was calculated by multiplying the difference in hepatic vein minus arterial levels of the mediators by the hepatosplanchnic flow . Systemic ( thermodilution ) and total hepatosplanchnic blood flow ( using indocyanine green [ICG]-dilution method ) and gastric intramucosal pH ( pHi ) were assessed preoperatively , 4 , 24 , and 36 h postoperatively . Of a total of 26 patients , 6 patients developed hepatic dysfunction after their abdominal surgery ( mean 6 days postoperatively ) . The number of sepsis-related deaths and postoperative days on the ventilator were significantly higher in this group . A higher production of IL-8 , TNF-receptor-75 and 55 in the hepatosplanchnic area in the HD+ subgroups was found , which preceded the development of organ dysfunction ( P = 0.04 , P = 0.02 , and P = 0.02 , respectively ) . Moreover , the uptake of s-ICAM-1 was significantly increased in this subgroup . Furthermore , total hepatosplanchnic blood flow was significantly higher and pHi was significantly lower in the HD+ group , whereas global hemodynamic data were similar in the two subgroups . In conclusion , the development of postoperative organ dysfunction is preceded by an increased regional inflammatory response , indicated by an increased soluble TNF-receptor shedding and IL-8 production from the hepatosplanchnic area together with an increased uptake of s-ICAM-1 . Moreover , an increased total hepatosplanchnic blood flow with intramucosal acidosis was associated with this regional inflammatory response INTRODUCTION For systematic elucidation of serial changes in neutrophil-endothelial activation markers as well as to investigate the correlationship among the inflammation markers , disseminated intravascular coagulation ( DIC ) , and multiple organ dysfunction syndrome ( MODS ) in patients with sepsis , we made this prospect i ve study . MATERIAL S AND METHODS Forty-five patients with sepsis , severe sepsis , and septic shock were subdivided into two groups , 27 with DIC and 18 without DIC . Eight normal healthy volunteers served as control subjects . Serial levels of soluble L- , P- , and E-selectins , intercellular adhesion molecule-1 ( sICAM-1 ) , vascular cell adhesion molecule-1 ( sVCAM-1 ) , thrombomodulin ( sTM ) , and neutrophil elastase were measured within 12 h after the diagnosis of sepsis ( day 0 ) and on days 1 - 4 after the diagnosis . The numbers of systemic inflammatory response syndrome ( SIRS ) criteria that patients met and the DIC score were determined simultaneously . RESULTS Acute Physiology and Chronic Health Evaluation ( APACHE ) II score was identical between the two groups . In the DIC patients , higher DIC scores , lower platelet counts , and more maximum numbers of SIRS criteria being met were observed compared with the non-DIC patients . The incidence of MODS and the number of the dysfunctioning organs were higher in the patients with DIC than those without DIC , and the DIC patients had poor outcome . Soluble L-selectin ( sL-selectin ) levels in both groups tended to be lower than those in the control subjects . All other parameters both in the two groups were continuously higher than those in the control subjects during study period . The levels of soluble E-selectin ( sE-selectin ) , sICAM-1 , sVCAM-1 , neutrophil elastase , and sTM were more elevated in the DIC patients than those in the non-DIC patients . There were no differences in the sP-selectin levels between the two groups ; however , more increased sP-selectin levels per platelet were found in the DIC patients compared with the non-DIC patients . Maximum DIC scores in the DIC group positively correlated with the peak levels of neutrophil elastase and sTM and the number of the dysfunctioning organs . CONCLUSIONS We found close relations among the neutrophil-endothelial cell interactions , DIC , and MODS in patients with sepsis , severe sepsis , and septic shock . The results indirectly confirm the concept that DIC can produce organ dysfunction and that DIC reflects an inflammatory disorder of the microvasculature Endothelial activation and damage are common endpoints of a complex process that may result in multiple organ dysfunction syndrome ( MODS ) . The influence of continuous intravenous heparinization on plasma levels of circulating adhesion molecules was studied in 28 trauma patients ( injury severity score between 15 and 25 points ) and 28 sepsis patients secondary to abdominal surgery . According to a prospect i ve , r and omized sequence the patients received either unfractionated heparin ( aim : activated partial thromboplastin time ( aPTT ) approximately 2 x normal ) ( trauma-heparin ( n = 14 ) ; sepsis-heparin ( n = 14 ) ) or not ( trauma ( n = 14 ) ; sepsis ( n = 14 ) ) . Plasma levels of circulating soluble endothelial leukocyte adhesion molecule-1 ( sELAM-1 ) , vascular cell adhesion molecule-1 ( sVCAM-1 ) , intercellular adhesion molecule-1 ( slCAM-1 ) , and granule membrane protein-140 ( sGMP-140 ) were serially measured from arterial blood sample s for 5 days . Approximately 600 U/h of heparin were given to increase aPTT to approximately 60 s. Plasma levels of all adhesion molecules increased in all groups . This increase was significantly ( p < .05 ) highest in both sepsis groups ( sepsis : sELAM-1 : from 50+/-11 to 84+/-19 ng/mL ; slCAM-1 : 410+/-68 to 700+/-95 ng/mL ) , but did not differ significantly between the treated and nontreated patients ( sepsis-heparin : sELAM-1 : from 60+/-131 to 88+/-20 ng/mL ; slCAM-1 : from 398+/-99 to 686+/-119 ng/mL ) . Trauma patients showed a less pronounced increase in all adhesion molecules without differences between the two subgroups . Only sGMP-140 increased significantly ( p < .05 ) more in the trauma ( from 102+/-20 to 169+/-16 ng/mL ) than in the trauma-heparin group ( from 109+/-19 to 132+/-17 ng/mL ) . It is summarized that continuous heparinization with approximately 600 U/h did not attenuate the rise in circulating adhesion molecules in sepsis and trauma patients . The study findings suggest that heparin in this dose regimen may be unlikely to influence endothelial inflammation or endothelial function in critically ill patients Objective : Coagulation activation is an integral part of sepsis pathogenesis . Experimental data suggest that endothelial exposure to hypoxia activates coagulation . We aim ed to test the hypothesis that the quantity of exposure to global tissue hypoxia is associated with the degree of coagulation activation during early sepsis resuscitation . Design : Prospect i ve , multicenter cohort study . Setting : Emergency department and intensive care unit of three academic hospitals . Patients : Inclusion criteria were age older than 17 , acute infection with two or more signs of systemic inflammation , hypotension despite fluid challenge ( or lactate > 4 mM ) , and continuous central venous oxygen saturation ( Scvo2 ) monitoring for quantitative resuscitation . Exclusion criteria were anticoagulant or blood product administration . Measurements and Main Results : We recorded central venous oxygen saturation continuously for 0 to 6 hrs of resuscitation and calculated the area under the curve for central venous oxygen saturation < 70 % . We defined hypoxia exposure as exceeding the median area under the curve for the entire cohort . At 0 , 6 , and 24 hrs , we measured conventional coagulation biomarkers plus thrombin – antithrombin complex , plasmin – antiplasmin complex , tissue plasminogen activator , plasminogen activator inhibitor-1 , protein C , antithrombin , and endothelial markers ( E-selectin , intracellular adhesion molecule-1 , thrombomodulin ) . We compared changes during 0 to 6 hrs and 0 to 24 hrs in biomarkers between hypoxia exposure and nonexposure groups . We enrolled 40 patients ( 60 % requiring vasopressors ; 30 % mortality ) . We found that exposure to hypoxia alone was not associated with a significant degree of coagulation activation . However , in secondary analyses we found that exposure to arterial hypotension induced E-selectin and thrombin – antithrombin complex , whereas concomitant exposure to both hypotension and hypoxia was associated with amplification of E-selectin and thrombomodulin , and a reduction in protein C. Conclusion : In this sample of patients undergoing quantitative resuscitation for sepsis , we found that exposure to global tissue hypoxia ( as quantified by low central venous oxygen saturation ) was not associated with major coagulation activation . Further investigation to eluci date the clinical factors that trigger or intensify the procoagulant response to sepsis is warranted Objective : Endothelial damage and detachment of endothelial cells are known to occur in septic patients . Thus , recruitment of circulating endothelial progenitor cells ( cEPCs ) to these lesions might have a beneficial effect on the clinical course in septic patients . Therefore , we were interested in whether EPCs , detected by flow cytometry , are increasingly mobilized during sepsis and if this mobilization is associated with clinical outcome . Design : Prospect i ve , nonr and omized study . Setting : Intensive care unit of a university hospital . Patients : Patients with ( n = 32 ) and without ( n = 15 ) sepsis and healthy volunteers ( n = 15 ) . Interventions : Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation , and cEPCs were characterized by three-color fluorescence flow cytometry using antibodies against CD133 , CD34 , and vascular endothelial growth factor receptor-2 . Serum concentrations of vascular endothelial growth factor , granulocyte macrophage-colony stimulating factor , and erythropoietin were determined by enzyme-linked immunosorbent assay . Severity of sepsis was assessed according to Acute Physiology and Chronic Health Evaluation II scoring . Measurements and Main Results : In septic patients , the number of cEPCs was significantly higher than in nonseptic intensive care unit patients ( p < .05 ) and healthy controls ( p < .02 ) . Nonsurvivors ( n = 8) , defined as death within 28 days after onset of sepsis , had significantly lower numbers of cEPCs than survivors ( n = 24 ) ( p < .0001 ) . The number of cEPCs was correlated with survival in septic patients . Serum vascular endothelial growth factor concentrations were significantly higher in septic patients compared with nonseptic intensive care unit patients and healthy controls ( p < .01 ) and correlated with the cEPC numbers ( p < .0001 ) . Similar findings were observed for granulocyte macrophage-colony stimulating factor and erythropoietin . Conclusions : Our data suggest that cEPC enumeration in peripheral blood of septic patients might be a valuable marker to assess the clinical outcome in these patients Objective The time course of circulating adhesion molecules was monitored in traumatized and sepsis patients . Design Prospect i ve , descriptive . Setting A surgical intensive care unit of a university hospital . Patients A total of 30 consecutive critically ill patients suffering either from trauma ( n=15 ) or postoperative sepsis ( n=15 ) . Interventions All patients were on continuous analgo-sedation and mechanical ventilation . Measurements and results From arterial blood sample s , plasma levels of soluble adhesion molecules [ endothelial leukocyte adhesion molecules ( sELAM-1 ) , intercellular adhesion molecule-1 ( sICAM-1 ) ] , and vascular cell adhesion molecule-1 ( sVCAM-1 ) were measured on the day of admission ( trauma patients ) or on the day of diagnosis of sepsis ( = baseline values ) , and during the following 5 days . In the trauma group , sELAM-1 ( 57.9±11.0 ng/ml ) and sVCAM-1 ( 698±93 ng/ml ) were within normal ranges at baseline , whereas they were markedly elevated in the sepsis group ( sELAM-1 : 340±95 ng/ml;sVCAM-1 ; 1,042±449 ng/ml ) . In the sepsis patients , sELAM-1 significantly decreased and sVCAM-1 increased , but remained almost unchanged in the trauma patients . Non-survivors showed markedly elevated plasma levels ofsELAM-1 and sVCAM-1.sICAM-1 was elevated in both groups at baseline and was higher in the sepsis group ( 1,266±261 ng/ml ) than in the trauma group . In the septic patients , sICAM-1 increased further ( 2,022±609 ng/ml ) and remained unchanged in the trauma group . All non-survivors showedsICAM-1 plasma levels of > 800 ng/ml . Conclusion Endothelial damage may result in multiple-organ dysfunction syndrome . Adhesion molecules are considered to be a cornerstone in this process . Trauma patients showed lower plasma levels of circulating adhesion molecules than did sepsis patients indicating more pronounced ( inflammatory related ) endothelial activation or damage in sepsis . Therapeutic modulation of circulating adhesion molecules may be of benefit to the patients outcome and therefore warrants further study OBJECTIVE The endothelial cell produces many bioactive compounds that are presumed to play important roles in the pathogenesis of the adult respiratory distress syndrome ( ARDS ) . We postulated that individuals with sepsis and trauma-two at-risk diagnoses for the development of ARDS -- might demonstrate differences in the degree of endothelial cell activity . DESIGN Prospect i ve cohort study . SETTING Intensive care unit patients in a tertiary , university-affiliated , city hospital . PATIENTS Fifty-five intensive care unit patients ( 19 with sepsis and 36 trauma patients ) . INTERVENTIONS Plasma measurements of three endothelial cell products -- von Willebr and factor antigen , soluble intercellular adhesion molecule-1 ( ICAM-1 ) , and soluble E-selectin-were performed within 8 hrs of patients meeting our inclusion criteria , and at the clinical onset of ARDS . MEASUREMENTS AND MAIN RESULTS Twenty-six percent of the septic patients and 25 % of the trauma patients developed ARDS . The median ( and 25 % to 75 % quartiles ) concentrations of all three mediators measured in the sepsis patients ( von Willebr and factor antigen 399 % [ 375 % to 452 % ] , ICAM-1 573 ng/mL [ 470 to 980 ] , and soluble E-selectin 180 ng/mL [ 81 to 340 ] ) were significantly higher ( p < .001 for each individual analysis ) than in the trauma patients ( von Willebr and factor antigen 256 % [ 217 % to 310 % ] , ICAM-1 148 ng/mL [ 113 to 210 ] , and soluble E-selectin 42 ng/mL [ 31 to 65 ng/ mL ] ) . In addition , neither the ICAM-1 nor soluble E-selectin concentrations measured in the trauma patients were different ( p = .17 and p = .24 , respectively ) from normal controls . In those patients who developed ARDS , the differences in the concentrations of all three endothelial cell mediators between the sepsis and trauma patients persisted ( p = .008 for von Willebr and factor antigen , p = .003 for ICAM-1 , and p = .003 for E-selectin ) . CONCLUSION These findings suggest that differences in endothelial cell activity exist between sepsis and trauma patients who are at risk for the development of ARDS Purpose Endothelial activation has emerged as an early event in the pathogenesis of microcirculatory dysfunction , capillary leakage and multi-organ dysfunction syndrome ( MODS ) . Angiopoietin-2 ( Ang-2 ) , a circulating antagonistic lig and of the endothelial-specific Tie2 receptor , has been identified as a non-redundant gatekeeper of endothelial activation . On the basis of our previous report demonstrating release of Ang-2 in endotoxemia and sepsis , we aim ed to study the utility of Ang-2 to serve as an outcome -specific biomarker in patients requiring renal replacement therapy ( RRT ) in the intensive care unit ( ICU ) . Methods We measured circulating Ang-2 by ELISA in 117 critically ill patients with AKI at inception of RRT in the ICU . Mortality , length of stay and renal recovery were prospect ively assessed during a study period of 28 days after the inception of RRT . Results Circulating Ang-2 levels were significantly higher in AKI patients with RIFLE category-Injury or -Failure , compared to patients with RIFLE category-Risk . Elevated levels of circulating Ang-2 correlated with impaired oxygenation , low mean arterial pressure , vasopressor dose and the sequential organ failure assessment ( SOFA ) score . Ang-2 concentrations were significantly higher in non-survivors than in survivors at day 0 and day 14 after initiation of RRT . Multivariate Cox regression and decision tree analyses confirmed a strong independent prognostic impact of elevated Ang-2 as a predictor of 28-day survival . Conclusions The results from this study indicate that circulating Ang-2 is as a strong and independent predictor of mortality in ICU patients with dialysis-dependent AKI Objective Elevated cytokine levels have been reported after ischemia/reperfusion injury and might cause a systemic inflammatory response syndrome ( SIRS ) after successful cardiopulmonary resuscitation ( CPR ) . It is unknown whether patients with SIRS after CPR exhibit higher levels of soluble adhesion molecules than patients without SIRS and whether SIRS or elevation of adhesion molecules is associated with outcome after CPR . We analyzed the relationships among various CPR-related variables , plasma levels of E- and P-selectin , the occurrence of SIRS after CPR , and the development of sepsis and outcome . Design Prospect i ve , controlled study . Setting Intensive care unit at a university hospital . Patients A total of 25 patients on the second day after successful CPR and 7 non-critically ill control patients . Interventions Blood sampling for determination of plasma levels of soluble ( s ) E- and P-selectin . Measurements and Main Results SIRS was a frequent finding after CPR ( 66 % of all patients ) unrelated to time until return of spontaneous circulation ( SIRS , 17 ± 13 mins ; no SIRS , 19 ± 16 mins;p = .761 ) , epinephrine dose ( SIRS , 4 ± 5 mg ; no SIRS , 5 ± 6 mg;p = .906 ) , or serum lactate level after CPR ( SIRS , 8.6 ± 2.6 mmol/L ; no SIRS , 8.7 ± 4.0 mmol/L;p = .174 ) . sP-selectin levels were higher in patients with SIRS ( 291.7 ± 227.4 ng/mL ) compared with patients without SIRS ( 113.4 ± 88.4 ng/mL;p = .018 ) or with non-critically ill patients ( 116.9 ± 33.4 ng/mL;p = .031 ) . Compared with non-critically ill control patients ( 42.8 ± 19.4 ng/mL ) , sE-selectin levels were higher in patients with ( 96.2 ± 47.3 ng/mL;p = .023 ) and without SIRS ( 99.5 ± 65.7 ng/mL;p = .030 ) . sP-selectin was higher in patients developing sepsis within 1 wk after CPR ( n = 9 ) than in patients without sepsis ( 350.2 ± 233.4 ng/mL vs. 158.5 ± 157.8 ng/mL;p = .022 ) and sE-selectin levels were higher in nonsurvivors ( n = 5 ) than in survivors ( 144.2 ± 62.4 ng/mL vs. 85.7 ± 45.3 ng/mL;p = .025 ) whereas SIRS was unrelated to the development of sepsis ( p = .4 ) and unrelated to survival ( p = .4 ) . Conclusions SIRS is an unspecific finding after CPR with only minor impact on outcome . Determination of sP- and sE-selectin early after CPR might help to identify patients at a high risk for sepsis or for an adverse outcome , respectively BACKGROUND : Vascular endothelial growth factor ( VEGF ) levels have been shown to be elevated in severe sepsis . We investigated the value of VEGF in predicting organ dysfunction and hospital mortality in adult patients with severe sepsis . METHODS : We conducted a prospect i ve observational cohort study in 24 closed multidisciplinary intensive care units ( ICU ) in Finl and . All ICU admission episodes ( 4500 ) were screened for severe sepsis from November 1 , 2004 , to February 28 , 2005 . Patients were eligible if they fulfilled the criteria for severe sepsis . RESULTS : Severe sepsis was found in 470 patients . Laboratory sample s were obtained after informed consent from 250 patients at study entry ( day 0 ) and from 215 patients after 72 h. These sample s were compared with sample s from 30 healthy individuals . The ICU mortality was 13.2 % and hospital mortality 26 % . Median serum VEGF concentrations on day 0 were 423 pg/mL ( interquartile range [ IQR ] 159 and 858 pg/mL ) , and after 72 h were 521 pg/mL ( IQR 182 and 1092 pg/mL ) , which were both higher than in healthy controls ( P = 0.029 and 0.003 , respectively ) . Low VEGF concentrations were associated with more severe renal and hematological dysfunction ( Sequential Organ Failure Assessment scores 3–4 compared with scores 0–2 ) . VEGF concentrations in day 0 and after 72 h were lower in nonsurvivors ( P = 0.01 and < 0.01 , respectively ) than in survivors , but the receiver operating characteristic curve analyses of concentrations of VEGF on day 0 and at 72 h revealed areas under the curve of 0.58 and 0.63 ( 95 % confidence limits 0.48–0.68 and 0.54–0.72 , P = 0.1 and 0.009 , respectively ) . CONCLUSIONS : VEGF concentrations are increased in patients with severe sepsis . Low concentrations are associated with hematological and renal dysfunction . VEGF concentrations were lower in nonsurvivors than in survivors , but did not adequately predict hospital mortality in patients with severe sepsis The sepsis syndrome represents a systemic response to infection and is defined as hypothermia ( temperature less than 96 degrees F ) or hyperthermia ( greater than 101 degrees F ) , tachycardia ( greater than 90 beat/min ) , tachypnea ( greater than 20 breath/min ) , clinical evidence of an infection site and with at least one end-organ demonstrating inadequate perfusion or dysfunction expressed as poor or altered cerebral function , hypoxemia ( PaO2 less than 75 torr ) , elevated plasma lactate , or oliguria ( urine output less than 30 ml/h or 0.5 ml/kg body weight.h without corrective therapy ) . One hundred ninety-one patients with the sepsis syndrome were evaluated prospect ively and comprised the placebo group of a multicenter trial of methylprednisolone in sepsis syndrome and septic shock . Forty-five percent of the patients were found to be bacteremic . Thirty-six percent of the patients were in septic shock ( sepsis syndrome plus a systolic BP less than 90 mm Hg or a decrease from baseline in systolic BP greater than 40 mm Hg ) on study entry . An additional 23 % of the patients developed shock after admission with 70 % doing so within 24 h of study entry . Shock reversal occurred with a 73 % frequency . Twenty-five percent of the patients developed the adult respiratory distress syndrome ( ARDS ) . Mortality for the patients with sepsis syndrome who did not develop shock was 13 % . Mortality for the groups of patients with shock on admission and shock postadmission was 27.5 % and 43.2 % , respectively . Forty-seven percent of the bacteremic patients developed shock after study admission compared to 29.6 % of the nonbacteremic patients ( p less than .05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Inflammatory mediators are released after trauma and may be related to the pathogenesis of sepsis . A prospect i ve combined study of the pattern of release of an inflammatory mediator , interleukin ( IL ) 6 , leucocyte activation ( polymorphonuclear leucocyte ( PMN ) CD11b receptor expression and plasma elastase‐α1 proteinase inhibitor complex ( E – α1PI ) ) and soluble endothelial adhesion molecule expression ( soluble E‐selectin ( sE‐selectin ) and soluble intracellular adhesion molecule 1 ( sICAM‐1 ) ) was performed in patients suffering blunt trauma without adult respiratory distress syndrome ( ARDS ) or multiple organ failure syndrome ( MOFS ) Prior murine and human studies suggest that vascular endothelial growth factor ( VEGF ) contributes to endothelial cell activation and severity of illness in sepsis . Furthermore , circulating levels of soluble VEGF receptor 1 ( sFLT ) levels were found to increase as part of the early response to sepsis in mice . The objective of the study was to evaluate the blood levels of free VEGF-A and sFLT in patients presenting to the emergency department ( ED ) with suspected infection and to assess the relationship of these levels with severity of illness and inflammation . It was a prospect i ve , observational study initiated in the ED of an urban , tertiary care , university hospital . Inclusion criteria were ( 1 ) ED patients aged 18 years or older and ( 2 ) clinical suspicion of infection . Eighty-three patients were enrolled in the study . The major findings were that ( 1 ) the mean VEGF and sFLT levels were increasingly higher across the following groups : noninfected control patients , infected patients without shock , and septic shock patients ; ( 2 ) initial and 24-h VEGF levels had a significant correlation with the presence of septic shock at 24 h ; ( 3 ) initial and 24-h sFLT levels correlated with Acute Physiology Age Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores initially and at 24 h ; and ( 4 ) VEGF and sFLT levels correlated with inflammatory cascade activation . This is the first report of sFLT as a potential new marker of severity in patients with sepsis . Vascular endothelial cell growth factor and its signaling axis are important in the endothelial cell response to sepsis , and further elucidation of these mechanisms may lead to advances in future diagnostic and therapeutic opportunities . ABBREVIATIONS-APACHE-Acute Physiology Age Chronic Health Evaluation ; ED-emergency department ; SOFA-Sepsis-related Organ Failure Assessment ; VEGF-vascular endothelial cell growth BACKGROUND Patients with chronic alcohol abuse constitute approximately 50 % of trauma care patients , and these patients have a two- to fourfold increase in posttraumatic infectious complications . Cytokines such as interleukin-6 ( IL-6 ) and interleukin-10 ( IL-10 ) and the adhesion molecule soluble endothelial selectin ( sE-selectin ) have been found to play an important role in the initial inflammatory response to trauma and the development of early and late multiple organ dysfunction syndrome ( MODS ) . The aim of this study was to compare the immune modulation and clinical relevance between chronic alcoholic and nonalcoholic patients following trauma . METHODS Sixty-three patients ( 37 alcohol abusers , 26 nonalcoholics ) were included in this prospect i ve controlled study . IL-6 , IL-10 , and sE-selectin were determined on admission and on days 2 , 4 , and 7 following admission to the ICU . RESULTS On admission to the ICU but not on the following days of the study period , plasma IL-6 , IL-10 , and sE-selectin were significantly elevated in chronic alcoholic patients compared with nonalcoholics . The incidence of MODS was significantly higher in chronic alcoholic patients ( 89 % vs. 50 % , p < 0.01 ) , whereas the incidence of pneumonia ( 35 % vs. 19 % , p < 0.17 ) and sepsis ( 14 % vs. 0 % , p < 0.07 ) did not reach statistical significance . CONCLUSION The significantly elevated levels of IL-6 , IL-10 , and sE-selectin in chronic alcoholic trauma patients on admission to the ICU could play an important role in the development of MODS in intensive care . In patients with high levels of inflammatory mediators , immune modulatory treatment before the development of MODS may be considered Objectives : a ) To evaluate in septic patients the blood levels of endocan , a circulating proteoglycan , which regulates leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interactions in vitro ; b ) to determine whether endocan could be used as a diagnostic and prognostic marker in sepsis in the intensive care unit ; and c ) to study kinetics of endocan secretion by endothelial cells in vitro after stimulation by soluble mediators involved in sepsis . Design : Prospect i ve observational study . Setting : Intensive care unit of the University Hospitals of Lille , France , and Geneva , Switzerl and . Patients : All patients admitted to the intensive care unit over a 6-month period with clinical evidence of severe sepsis or septic shock . Interventions : None . Measurements and Main Results : In vitro , we showed a sustained endocan secretion by endothelial cells after stimulation by lipopolysaccharide and tumor necrosis factor-&agr;. Circulating levels of endocan measured in 63 patients admitted to the intensive care unit with sepsis were significantly elevated compared with 20 healthy donors and seven patients with systemic inflammatory response syndrome : 2.71 ± 4.88 ng/mL vs. 0.77 ± 0.44 ng/mL vs. 0.68 ± 1.03 ng/mL ( median ± interquartile range , p < .001 ) . Endocan levels were higher in patients with septic shock ( 6.11 ± 12.99 ng/mL , n = 22 ) than in patients with severe sepsis ( 1.97 ± 7.8 ng/mL , n = 12 ) or sepsis ( 1.95 ± 1.63 ng/mL , n = 29 ) . Measurement of endocan at intensive care unit admission revealed higher levels in nonsurvivors ( n = 12 ) than in patients still alive 10 days later ( n = 51 , 6.98 ± 13.8 vs. 2.45 ± 4.09 , p < .01 ) . Conclusions : These results suggest that in septic patients , endocan blood level is related to the severity of illness and the outcome of the patient and may represent a novel endothelial cell dysfunction marker Previous studies found increased circulating levels of biomarkers related to endothelial cell activation in patients with sepsis , particularly in the most severe sepsis stages of sepsis shock . It remains unclear , however , whether this activation is mainly driven by sepsis-specific mechanisms or occurs as a generalized inflammatory response . The objective of this analysis was to compare patterns of biomarkers of endothelial cell activation in patients with hypotension due to sepsis and nonsepsis etiologies . This is a secondary analysis of a prospect i ve , observational cohort study including emergency department patients older than17 years with an episode of hypotension defined as any systolic blood pressure measurement less than 100 mmHg . Etiology of hypotension episodes was classified as sepsis or nonsepsis ( eg , cardiac or hemorrhagic ) . Endothelial activation biomarkers of cell adhesion ( E-selectin , vascular cell adhesion molecule 1 [ VCAM-1 ] , and intercellular adhesion molecule 1 [ ICAM-1 ] ) , coagulation ( plasminogen activator inhibitor 1 [ PAI-1 ] ) , and vascular endothelial growth factor ( VEGF ) signaling ( VEGF , soluble fms-like tyrosine kinase 1 [ sFLT-1 ] ) were assayed . A total of 161 patients were analyzed . Hypotension was classified as sepsis ( n = 69 ) , nonsepsis ( cardiac [ n = 35 ] , hemorrhagic [ n = 12 ] ) , or indeterminate ( n = 45 ) . With the exception of PAI-1 , median plasma levels of all endothelial markers were significantly higher in patients with sepsis compared with nonsepsis etiology ( P < 0.05 for all comparisons ) . Logistic regression analysis , adjusted for age , sex , mean blood pressure level , and mortality , confirmed a significant association of E-selectin ( odds ratio [ OR ] , 3.7 ; 95 % confidence interval [ CI ] , 1.7 - 7.8 , P < 0.001 ) and sFLT-1 ( OR , 2.0 ; CI , 1.1 - 3.8 ; P < 0.03 ) with sepsis etiology . Biomarkers VCAM-1 ( OR , 2.0 ; CI , 0.88 - 4.4 ; P = 0.1 ) , VEGF ( OR , 1.5 ; CI , 0.98 - 2.2 ; P = 0.06 ) , ICAM-1 ( OR , 1.5 ; CI , 0.9 - 2.6 ; P = 0.2 ) , and PAI-1 ( OR , 1.4 ; CI , 0.8 - 2.3 ; P = 0.2 ) did not reach statistical significance . This study found a sepsis-specific activation of endothelium activation markers , particularly E-selectin and sFLT-1 , in emergency department patients with hypotension . ABBREVIATIONS-ED-emergency department ; ICAM-1-soluble intercellular adhesion molecule 1 ; PAI-1-plasminogen activator inhibitor 1 ; sFLT-1-soluble fms-like tyrosine kinase 1 ; VCAM-1-soluble vascular cell adhesion molecule 1 ; VEGF-vascular endothelial growth PURPOSE This prospect i ve clinical study was design ed to compare interleukin 1 receptor antagonist ( IL-1ra ) and E-selectin concentrations in patients with severe acute pancreatitis to those with severe sepsis . MATERIAL S AND METHODS Nine consecutive patients with severe acute pancreatitis and 11 consecutive patients with severe sepsis admitted to a medical/surgical intensive care unit were included in the study . Plasma concentrations of IL-1ra and E-selectin were serially measured daily for 7 days or throughout their stay in the intensive care unit if shorter . RESULTS The concentrations of IL-1ra were significantly higher on admission in patients with severe sepsis compared with the patients with severe pancreatitis ( median levels 10,500 and 2,600 pg/mL , respectively , P = .007 ) . When the data from the first 3 days were analyzed using analysis of variance ( ANOVA ) , the levels of IL-1ra and E-selectin were similar in both groups . The concentrations of IL-1ra and E-selectin correlated to the development of multiorgan dysfunction as assessed by sequential organ failure assessment ( SOFA ) score ( P = .032 and .043 , respectively ) . CONCLUSION This study shows that IL-1ra and E-selectin are released in acute severe pancreatitis , and the levels seem to be comparable to those in patients with severe sepsis . Concentrations of IL-1ra and E-selectin correlate to the development of multiorgan failure as indicated by high SOFA scores during the first week of disease Objective : Angiopoietin (Ang)‐2 is an endothelium‐specific growth factor , regulated by proinflammatory stimuli , that destabilizes vascular endothelium and increases vascular leakage ; consequently , Ang‐2 may contribute to sepsis pathophysiology . We have studied 1 ) serum Ang‐2 levels in critically‐ill patients and investigated potential relationships with inflammatory mediators and indices of disease severity and 2 ) the effect of sepsis‐related inflammatory mediators on Ang‐2 production by lung endothelium in vitro . Design : Prospect i ve clinical study followed by cell culture studies . Setting : General intensive care unit and research laboratory of a university hospital . Subjects : Human and bovine lung microvascular endothelial cells and 61 patients ( 32 men ) . Patients were grouped according to their septic stage as having : no systemic inflammatory response syndrome ( n = 6 ) , systemic inflammatory response syndrome ( n = 8) , sepsis ( n = 16 ) , severe sepsis ( n = 18 ) , and septic shock ( n = 13 ) . Interventions : Cells were exposed to lipopolysaccharide , tumor necrosis factor‐&agr ; , and interleukin‐6 . Measurements and Main Results : Patients ’ serum Ang‐2 levels were significantly increased in severe sepsis as compared with patients with no systemic inflammatory response syndrome or sepsis ( p < .05 by analysis of variance ) . Positive linear relationships were observed with : serum tumor necrosis factor‐&agr ; ( rs = 0.654 , p < .001 ) , serum interleukin‐6 ( rs = 0.464 , p < .001 ) , Acute Physiology and Chronic Health Evaluation II score ( rs = 0.387 , p < .001 ) , and Sequential Organ Failure Assessment score ( rs = 0.428 , p < .001 ) . Multiple regression analysis revealed that serum Ang‐2 is mostly related to serum tumor necrosis factor‐&agr ; and severe sepsis . Treatment of human lung microvascular endothelial cells with all mediators result ed in a concentration‐dependent Ang‐2 reduction . Treatment of bovine lung microvascular endothelial cells with lipopolysaccharide and tumor necrosis factor‐&agr ; increased Ang‐2 release , and interleukin‐6 reduced basal Ang‐2 levels . Conclusions : First , patients ’ serum Ang‐2 levels are increased during severe sepsis and associated with disease severity . The strong relationship of serum Ang‐2 with serum tumor necrosis factor‐&agr ; suggests that the latter may participate in the regulation of Ang‐2 production in sepsis . Second , inflammatory mediators reduce Ang‐2 release from human lung microvascular endothelial cells , implying that this vascular bed may not be the source of increased Ang‐2 in human sepsis |
1,621 | 27,874,942 | Among the non-surgical , non-pharmacological treatment modalities , the breathing training on diaphragm could play an important role in selected patients to manage the symptoms of GERD | OBJECTIVE Gastroesophageal reflux disease ( GERD ) represents one of the most common gastrointestinal disorders , but is still a challenge to cure .
Proton pump inhibitors ( PPIs ) are currently the GERD 's st and ard treatment , although not successful in all patients ; some concerns have been raised regarding their long term consumption .
Recently , some studies showed the benefits of inspiratory muscle training in increasing the lower esophageal sphincter pressure in patients affected by GERD , thereby reducing their symptoms . | OBJECTIVES : The lower esophageal sphincter ( LES ) , surrounded by diaphragmatic muscle , prevents gastroesophageal reflux . When these structures become incompetent , gastric contents may cause gastroesophageal reflux disease ( GERD ) . For treatment , lifestyle interventions are always recommended . We hypothesized that by actively training the crura of the diaphragm as part of the LES using breathing training exercises , GERD can be positively influenced . METHODS : A prospect i ve r and omized controlled study was performed . Patients with non-erosive GERD or healed esophagitis without large hernia and /or previous surgery were included . Patients were r and omized and allocated either to active breathing training program or to a control group . Quality of life ( QoL ) , pH-metry , and on-dem and proton pump inhibitor ( PPI ) usage were assessed at baseline and after 4 weeks of training . For long-term follow-up , all patients were invited to continue active breathing training and were further assessed regarding QoL and PPI usage after 9 months . Paired and unpaired t-test was used for statistical analysis . RESULTS : Nineteen patients with non-erosive GERD or healed esophagitis were r and omized into two groups ( 10 training group and 9 control group ) . There was no difference in baseline patient characteristics between the groups and all patients finished the study . There was a significant decrease in time with a pH<4.0 in the training group ( 9.1±1.3 vs. 4.7±0.9 % ; P<0.05 ) , but there was no change in the control group . QoL scores improved significantly in the training group ( 13.4±1.98 before and 10.8±1.86 after training ; P<0.01 ) , but no changes in QoL were seen in the control group . At long-term follow-up at 9 months , patients who continued breathing exercise ( 11/19 ) showed a significant decrease in QoL scores and PPI usage ( 15.1±2.2 vs. 9.7±1.6 ; 98±34 vs. 25±12 mg/week , respectively ; P<0.05 ) , whereas patients who did not train had no long-term effect . CONCLUSIONS : We show that actively training the diaphragm by breathing exercise can improve GERD as assessed by pH-metry , QoL scores and PPI usage . This non-pharmacological lifestyle intervention could help to reduce the disease burden of GERD Background The risk for acidic reflux is mainly determined by the position of the gastric acid pocket . It was hypothesised that compounds affecting proximal stomach tone might reduce gastro-oesophageal reflux by changing the acid pocket position . Objective To study the effect of azithromycin ( Azi ) on acid pocket position and acid exposure in patients with gastro-oesophageal reflux disease ( GORD ) . Methods Nineteen patients with GORD were included , of whom seven had a large hiatal hernia ( ≥3 cm ) ( L-HH ) and 12 had a small or no hiatal hernia ( S-HH ) . Patients were r and omised to Azi 250 mg/day or placebo during 3 days in a crossover manner . On each study day , reflux episodes were detected using concurrent high-resolution manometry and pH-impedance monitoring after a st and ardised meal . The acid pocket was visualised using scintigraphy , and its position was determined relative to the diaphragm . Results Azi reduced the number of acid reflux events ( placebo 8.0±2.2 vs Azi 5.6±1.8 , p<0.01 ) and postpr and ial acid exposure ( placebo 10.5±3.8 % vs Azi 5.9±2.5 % , p<0.05 ) in all patients without affecting the total number of reflux episodes . Acid reflux occurred mainly when the acid pocket was located above , or at the level of , the diaphragm , rather than below the diaphragm . Treatment with Azi reduced hiatal hernia size and result ed in a more distal position of the acid pocket compared with placebo ( below the diaphragm 39 % vs 29 % , p=0.03 ) . Azi reduced the rate of acid reflux episodes in patients with S-HH ( 38 % to 17 % ) to a greater extent than in patients with L-HH ( 69 % to 62 % , p=0.04 ) . Conclusion Azi reduces acid reflux episodes and oesophageal acid exposure . This effect was associated with a smaller hiatal hernia size and a more distal position of the acid pocket , further indicating the importance of the acid pocket in the pathogenesis of GORD . clinical trial registration http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=1970 NTR1970 The crural diaphragm ( CD ) is an essential component of the esophagogastric junction ( EGJ ) , and inspiratory exercises may modify its function . This study 's goal is to verify if inspiratory muscle training ( IMT ) improves EGJ motility and gastroesophageal reflux ( GER ) . Twelve GER disease [ GERD ; 7 males , 20 - 47 yr , 9 esophagitis , and 3 nonerosive reflex disease ( NERD ) ] and 7 healthy volunteers ( 3 males , 20 - 41 yr ) performed esophageal pH monitoring , manometry , and heart rate variability ( HRV ) studies . A 6-cm sleeve catheter measured average EGJ pressure during resting , peak inspiratory EGJ pressures during sinus arrhythmia maneuver ( SAM ) and inhalations under 17- , 35- , and 70-cmH2O loads ( TH maneuvers ) , and along 1 h after a meal . GERD patients entered a 5-days-a-week IMT program . One author scored heartburn and regurgitation before and after IMT . IMT increased average EGJ pressure ( 19.7 ± 2.4 vs. 29.5 ± 2.1 mmHg ; P < 0.001 ) and inspiratory EGJ pressure during SAM ( 89.6 ± 7.6 vs. 125.6 ± 13.3 mmHg ; P = 0.001 ) and during TH maneuvers . The EGJ-pressure gain across 35- and 70-cmH2O loads was lower for GERD volunteers . The number and cumulative duration of the transient lower esophageal sphincter relaxations decreased after IMT . Proximal progression of GER decreased after IMT but not the distal acid exposure . Low-frequency power increased after IMT and the higher its increment the lower the increment of supine acid exposure . IMT decreased heartburn and regurgitation scores . In conclusion , IMT improved EGJ pressure , reduced GER proximal progression , and reduced GERD symptoms . Some GERD patients have a CD failure , and IMT may prove beneficial as a GERD add-on treatment OBJECTIVES The prevalence of gastroesophageal reflux disease ( GERD ) in patients with laryngopharyngeal disorders is probably greater than realized . STUDY DESIGN Prospect i ve study . METHODS To investigate the incidence of gastroenterological diseases including GERD in patients complaining of nonspecific laryngopharyngeal symptoms , laryngological examinations and gastroenterological evaluation with esophagogastroduodenoscopy were performed in 30 patients who refused to undergo 24-hour pH monitoring . Therapeutic intervention by behavioural and dietary modifications , antireflux medication , and eradication of Helicobacter pylori were assessed for changes in laryngeal findings and relief of symptoms . RESULTS Posterior laryngitis was present in 26 patients and in 19 of them was accompanied by erythema and edema of the interarytenoid region . Gastroenterological diseases such as GERD ( 43 % ) , hiatal hernia ( 43 % ) , and Helicobacter pylori-positive antrum gastritis ( 23 % ) were confirmed in 22 ( 73 % ) cases by esophagogastroduodenoscopy and histological examination of biopsy specimens . Medical antireflux treatment and eradication of Helicobacter pylori result ed in a remarkably therapeutic success rate of 90 % because there was resolution of laryngopharyngeal symptoms and laryngeal findings in 20 of 22 patients with gastroenterological diseases for the mean follow-up period of 8 months . CONCLUSIONS Laryngopharyngeal symptoms can be predictors of gastroesophageal diseases and GERD because the most frequent underlying cause is supposed to be associated with posterior laryngitis . Medical antireflux treatment is effective for relief of symptoms and mucosal healing of posterior laryngitis The treatment of gastroesophageal reflux disease may be clinical or surgical . The clinical consists basically of the use of drugs ; however , there are new techniques to complement this treatment , osteopathic intervention in the diaphragmatic muscle is one these . The objective of the study is to compare pressure values in the examination of esophageal manometry of the lower esophageal sphincter ( LES ) before and immediately after osteopathic intervention in the diaphragm muscle . Thirty-eight patients with gastroesophageal reflux disease - 16 su bmi tted to sham technique and 22 su bmi tted osteopathic technique - were r and omly selected . The average respiratory pressure ( ARP ) and the maximum expiratory pressure ( MEP ) of the LES were measured by manometry before and after osteopathic technique at the point of highest pressure . Statistical analysis was performed using the Student 's t-test and Mann-Whitney , and magnitude of the technique proposed was measured using the Cohen 's index . Statistically significant difference in the osteopathic technique was found in three out of four in relation to the group of patients who performed the sham technique for the following measures of LES pressure : ARP with P= 0.027 . The MEP had no statistical difference ( P= 0.146 ) . The values of Cohen d for the same measures were : ARP with d= 0.80 and MEP d= 0.52 . Osteopathic manipulative technique produces a positive increment in the LES region soon after its performance BACKGROUND Proton pump inhibitors ( PPIs ) are a major breakthrough in the medical management of gastroesophageal reflux disease ( GERD ) . In several patients with non erosive reflux disease symptoms ( NERD ) the response to PPIs is partial or limited and symptoms relief needs the administration of additional medications . AIM The aim of this study was to evaluate the effect of a new medical device , based on an oral fixed combination of hyaluronic acid and chondroitin-sulphate ( HA+CS ) , in a bioadhesive carrier , in adults with symptoms of non erosive gastroesophageal reflux and with a low response to PPIs . PATIENTS AND METHODS Twenty patients who had experienced heartburn and /or acid regurgitation for at least 3 days during a 7 day run-in period , without endoscopic mucosal breaks , were r and omized in a double blind crossover study to receive four daily doses of a fixed oral combination of HA+CS and placebo for 14 days . Relief of cardinal symptoms of GERD was evaluated at the end of each period . RESULTS A significant greater Sum of Symptoms Intensity Difference , compared to placebo , was observed after HA+CS treatment ( -2.7 vs 0.5 - p < 0.01 ) , being both heartburn ( -1.6 vs 0.5 - p < 0.03 ) and acid regurgitation ( -1.1 vs 0.1 - p < 0.03 ) significantly improved by the medical device . A speed of action ≤ 30 min was significantly more frequently reported by patients during HA+CS administration than with placebo ( 60 % vs 30 % - p = 0.05 ) . Total disappearance of symptoms was observed in 50 % of the patients compared to 10 % during placebo administration ( p = 0.01 between group comparison ) . CONCLUSIONS A fixed combination of HA+CS has demonstrated to be effective in gastroesophageal reflux control , with a rapid onset of action |
1,622 | 17,636,687 | Pooling of results indicated no statistically significant difference in the incidence of wound infection , haematoma , dehiscence or re-operations between those allocated to drains and the un-drained wounds .
Blood transfusion was required more frequently in those who received drains .
The need for reinforcement of wound dressings and the occurrence of bruising were more common in the group without drains .
There is insufficient evidence from r and omised trials to support the routine use of closed suction drainage in orthopaedic surgery . | BACKGROUND Closed suction drainage systems are frequently used to drain fluids , particularly blood , from surgical wounds .
The aim of these systems is to reduce the occurrence of wound haematomas and infection .
OBJECTIVES To evaluate the effectiveness of closed suction drainage systems for orthopaedic surgery . | In a prospect i ve , r and omized study , 58 patients with primary cemented hip arthroplasty and 39 patients with primary cemented knee arthroplasty were divided into groups with postoperative closed-suction drainage and without drainage . There was no difference in healing of the wounds , postoperative blood transfusions , complications , or range of motion . Although there was more soaked dressing requiring reinforcements in the groups without drainage , as a result of this study , we no longer use drains in uncomplicated cemented primary hip and knee arthroplasties for osteoarthritis Abstract A prospect i ve evaluation of 98 patients who had undergone a total hip or knee arthroplasty was conducted to assess the effect of postoperative suction drainage . Sixty-six patients undergoing elective total hip arthroplasty and 32 patients undergoing total knee replacement were r and omly allocated to undergo either suction drainage or no drainage of the wound . Statistical analysis of the results showed no difference in wound healing , severity of wound haematoma , postoperative blood transfusion requirement , range of motion and duration of the hospitalization between the two groups . We conclude that the use of closed suction drainage provides no apparent advantage after uncomplicated total hip or knee arthroplasty Purpose of the study Suction drainage in bipolar arthroplasty for hip fracture is st and ard procedure despite the lack of a solid scienfific basis . No study is reported in the literature demonstrating an advantage of systematic drainage . The aim of this work was to search for reasons why this conventional practice should be continued , Material and method es A prospect i ve r and omized stydt in a homogeneous consecutive group of patients hospitalized in our unit for hip fracture were included in the study from January 1995 through January 1999 . Among the 183 patients , 97 were excluded ( hemostasis disorders or anticoagulant treatment , multiple fractures , preoperative anemia with Hg < 9.5 g/dl , postponed operation ) . For the 86 included patients , the posterolateral Moore access was used to implant a sealed intermediary prosthesis . According to r and om selection , drainage was then installed or not . Outcome criteria were number of reoperations , hemoglobin level on DO , D1 , D2 , D5 , and D10 , number of patients requiring transfusion and number of packed red cell units in each group , and finally , temperature as reflecting presence of possible hematome ( DO , D2 , D5 , D10 ) . Results The two groups were similar for age and sex . There were no reoperations for hematoma or superficial infection and only one patient was reoperated for early dislocation in the group without drainage . Twenty-seven patients had transfusions , 14 in the drainage group and 13 in the no drainage group ; mean number of packed red cell units was 2 . Hemoglobin level fell similarly in the two groups in DO ( 2.1 versus 1.9 ) , D2 ( 2.5 versus 2.4 ) , D ( 2.7 versus 2.7 ) , D10 ( 2.4 versus 2.6 ) as did mean temperatures . Discussion We were thus unable to demonstrate any advantage of using suction drainage in bipolar arthroplasty for hip fracture when using more access . This is in agreement with reports in the literature . Exception the simplification of nursing care by not using drains , the cost savings can be considerable in light of the number of patients treated . We recommend that systematic use of suction drainage be discontinued in bipolar arhtroplasty for hip fracture The routine use of surgical drains in total hip arthroplasty remains controversial . They have not been shown to decrease the rate of wound infection significantly and can provide a retro grade route for it . Their use does not reduce the size or incidence of post-operative wound haematomas . This prospect i ve , r and omised study was design ed to evaluate the role of drains in routine total hip arthroplasty . We investigated 552 patients ( 577 hips ) undergoing unilateral or bilateral total hip arthroplasty who had been r and omised to either having a drain for 24 hours or not having a drain . All patients followed st and ardised pre- , intra- , and post-operative regimes and were independently assessed using the Harris hip score before operation and at six , 18 and 36 months follow-up . The rate of superficial and deep infection was 2.9 % and 0.4 % , respectively , in the drained group and 4.8 % and 0.7 % , respectively in the undrained group . One patient in the undrained group had a haematoma which did not require drainage or transfusion . The rate of transfusion after operation in the drained group was significantly higher than for undrained procedures ( p < 0.042 ) . The use of a drain did not influence the post-operative levels of haemoglobin , the revision rates , Harris hip scores , the length of hospital stay or the incidence of thromboembolism . We conclude that drains provide no clear advantage at total hip arthroplasty , represent an additional cost , and expose patients to a higher risk of transfusion We report on a prospect i ve r and omized trial on the effect of wound drains on wound healing following surgery for proximal femoral fractures . One hundred and seventy-seven consecutive patients admitted to Queen 's Medical Centre Nottingham , undergoing AO dynamic hip screw ( DHS ) or hemiarthroplasty were r and omized whether or not to receive wound drainage . Wound healing was assessed in terms of ultrasound examination , the ASEPSIS wound score system and overt infection rates . All patients were followed up at 6 weeks and 6 months . Ultrasound examinations showed that drains were indeed ineffective in preventing haematoma formation , the first time this has been demonstrated objective ly . However , using drains failed to prevent late seroma formation . Patients who received wound drainage showed statistically better wound healing on the ASEPSIS wound scoring system and a reduced infection rate . The ASEPSIS scores on day 2 and 5 postoperatively proved an accurate predictor of poor wound healing . This study conflicts with previous smaller studies which failed to show an effect of wound drainage upon wound healing , and strongly supports the use of wound drains In a r and omized clinical study on 40 intraarticular knee joint drainages the effect of a high vacuum , middle vacuum , low vacuum and suction free drainages were examined . The maximum of the volume that was drained had been in the group of the suction free drainages . Drains with a long period of suction had a minimum of evaluated ultrasonographic effusion in the knee joint . The group with high vacuum was obviously not as long as open as in the other groups . Thrombi in the drainages could be found in every group . This refers to the observation that the finding of adherent thrombi is related to the material the drain is made of . Adherent thrombi decrease the possibility of secretion , not adherent thrombi do not decrease suction volume . Referring to these results it is obvious that not the high-vacuum drainage is the matter of choice for intraarticular drains . The suction-free drainages or drains with reduced vacuum have more advantages in respect to simple , secure and fast implantation and h and ling A prospect i ve study of thirty-eight patients ( seventy-six knees ) who had had a primary bilateral total knee replacement and twelve patients ( twenty-four hips ) who had had a primary bilateral total hip replacement was conducted to assess the effect of postoperative suction drainage on wound-healing . A suction drain was placed on each patient 's right operative wound , while no drains were used on the left . Otherwise , the same operative technique and method of closure were used in all wounds . Statistical analysis of the results showed no difference between the two sides with regard to the incidences of swelling or persistent drainage . Return of active function of the quadriceps and of range of motion of the knee in patients who had had a total knee replacement was also unaffected by the use of suction drains . We concluded that the routine use of suction drains for wounds is unnecessary after uncomplicated total joint arthroplasty One hundred fifteen consecutive patients undergoing TKR were divided into two groups to determine whether blood loss and transfusion in total knee replacement ( TKR ) using adrenaline with saline infiltration would be less than TKR with tourniquet and drain . Group 1 , composed of 60 patients , received 2.5 mg of 1:1000 adrenaline diluted in 500 mL of normal saline , which was infiltrated into the skin , subcutaneous tissues , and capsule before surgical incision . No tourniquets or postoperative drains were used . Group 2 , composed of 55 patients , had a tourniquet and postoperative drain . Thromboprophylaxis with low molecular weight heparin also was used . Pre- and postoperative hemoglobin , blood loss , hematocrit , and transfusion requirements were studied in both groups ; in group 2 , blood loss in the drains also was noted . Average preoperative hemoglobin and hematocrit in the two groups were 13.7 g/dL and 39.3 g/dL , respectively , and 13.5 % and 39 % , respectively . Average intraoperative blood loss was 290 mL in group 1 and 377.7 mL in group 2 ( P<.005 ) . Postoperative blood loss in group 1 was < 50 mL based on dressing soakage and 297.7 mL in group 2 ( P<.005 ) . Average postoperative hemoglobin and hematocrit in the two groups were 10.6 g/dL and 8.4 g/dL , respectively , and 35.4 % and 31.1 % , respectively . Transfusion rates were 3.3 % and 23.6 % , respectively ( P<.005 ) . The average volume transfused was 1.2 U. Adrenaline and saline infiltration is safe and helps reduce intraoperative blood loss . Suction drain use for surgical wounds after primary , uncomplicated TKR is question able The goal of this study is to report our experience with the use of suction drainage for various arthroscopic knee procedures . One hundred and ninety patients who underwent arthroscopic knee procedures participated in the study , and were divided into two groups ( Group 1 : Suction drainage , Group 2 : No suction drainage ) . For every patient , the following parameters were recorded : age , gender , operative time , tourniquet or pump use , the amount of fluid collected in the hemovac drain , presence of meniscal tear , type of the operative procedure , date of the operation , and presence of effusion at the follow-up . Statistical analysis was performed to detect any significant statistical difference between the amount of fluid collected in the hemovac drain and the other mentioned parameters in Group 1 ; and these patients were divided into four subgroups to facilitate the statistical evaluation between the procedures and the amount of fluid collected in the hemovac drain . The partial meniscectomy subgroup had significantly lower amounts of collected fluid when compared to the subtotal meniscectomy subgroup . Drilling of the osteochondral faces led to significantly higher amounts of fluid when compared to non-drilling cases . Use of an infusion pump during surgery and shorter operation time led to lower amounts of fluid to be collected . No case in either main group suffered from effusion at the follow-up . Our investigation demonstrated that in different arthroscopic interventions , variable amounts of fluid can be collected in the hemovac drains . Subtotal meniscal resection , drilling of the osteochondral faces and longer duration of the operation increase the amount of fluid . In cases of partial meniscal resection and /or chondral debridement , limited synovial and plica resection , suction drainage is unnecessary A r and omized , controlled study compared the effects of wound compression with drainage after primary total hip arthroplasty . In 51 patients , an inflatable cuff was placed over the wound underneath a girdle ( System Calmed , Calmed AB , Askim , Sweden ) . Control patients had wound drainage ( n = 54 ) . Preoperative and intraoperative variables did not differ between groups . Total blood loss was calculated using hemoglobin balance ; with compression it was 1510 + /- 656 mL ( mean + /- SD ) and in controls 1695 + /- 712 mL ( P = .13 ) . However , less blood was transfused in the compression group ( P = .05 ) . Wound infection was seen in 2 patients with compression and in 3 controls . Deep venous thrombosis occurred in 3 controls . Wound discharge was more frequent in controls ( 19/54 vs 8/51 ; P = .04 ) . Thus , wound compression had no obvious negative effects and reduced wound discharge and need for transfusion . It may replace drainage after total hip arthroplasty A prospect i ve , r and omized study was performed to assess the effectiveness of postoperative closed suction drainage . One hundred and twelve consecutive procedures involving autologous iliac-crest bone graft were performed , from December 29 , 1992 , to July 1 , 1993 , following a traumatic injury of the spine in 108 patients . Sixty of the sites from which the bone graft had been obtained were drained with a single large Hemovac device . The drains were maintained for two to five days postoperatively . The remaining fifty-two incisions were closed without a drainage device . All patients were evaluated clinical ly for problems with wound-healing . The incisions were considered to be healed when they had been asymptomatic for one year . Of eleven patients who had problems with wound-healing , six had been managed with a drain and five had not . The findings of this study do not support the routine use of drainage at the donor sites of iliac-crest bone grafts We studied the management of postoperative drainage after total knee replacement ( TKR ) . 90 primary total knee joint arthroplasties were prospect ively r and omized into 3 groups : a ) no drain , b ) an autotransfusion system , c ) a st and ard disposable closed suction drainage system . We monitored hemoglobin and hematocrit values , drainage volume and transfusions ( homologous and autologous ) , range of knee motion , knee swelling and hospital stay . Parameters were recorded preoperatively , days 0 - 8 and 4 months postoperatively . No significant differences were seen between the groups in any of the parameters measured . The results show no benefit from using postoperative drainage systems in knee arthroplasties . Savings of SEK 400 ( USD 55 ) per patient would have result ed if drains had not been used at all A prospect i ve trial has been carried out to determine the value of suction drainage in the operation of meniscectomy . One hundred operations were analysed , in half of which drains had been used . The use of the drain could not be shown to result in any sustained advantages . The dem and for analgesics after the operation was reduced but not to a statistically significant level . The size of the early effusion was significantly reduced , but this benefit was lost when the knee was mobilised . The return of power to the quadriceps and of movement to the knee were not hastened . The average volume of fluid drained was 134 millilitres and it has been shown that forty-eight hours is a suitable time for removal of the drain . The use of suction drainage is not advocated for the uncomplicated operation of meniscectomy Forty-four patients undergoing elective hip joint operation were analyzed to assess whether a new slit-suction drainage is less painful than the regular Redon-suction drainage . Main endpoint of the study was the effectiveness to draw off secretion and the pain at the time of removal of the drainage . Other endpoint was the rate of postoperative complications . At the time of removal patients with slit drain rarely complained about pain ( p < 0.01 ) . On contrary , patients with Redon drain always complained about pain . Clotting were seldom shown in slit drains and were frequently shown in Redon drains . Both slit drains and Redon drains were effective to drain secretion . As the new slit drain was more comfortable for patients following hip joint repair slit drain should always be used as suction drainage Abstract . Sixty patients were operated on for primary gonarthrosis by means of a cemented , posterior cruciate preserving total knee and were r and omly allocated to postoperative drainage or nondrainage . The primary criterion was duration of hospital stay . Secondary criteria included serial evaluation of knee pain , knee flexion , knee circumference , calculated blood loss after 7 days , complications , reoperations , and the need for blood transfusions . There was no difference between the two groups in any of the criteria during the entire follow-up . There was a nonsignificant trend to a decreased calculated blood loss in the nondrained group and significantly less transfused blood units in the nondrained group . Lack of drainage does not increase complication risk after total knee prosthesis implantation . We therefore recommend using no routine drainage after this procedure A prospect i ve study of 48 patients ( 96 hips ) who had undergone primary simultaneous bilateral total hip arthroplasty was conducted to assess the effect of postoperative suction drainage on wound healing and infection . A suction drain was placed by r and omization of the drained versus undrained side . The same surgical technique was used in all total hip arthroplasty wounds . Statistical analysis of the results showed significant differences with respect to drainage from the wound , soaked dressings requiring reinforcements , ecchymosis , and erythema about the wound in the group without drainage . There was no specific correlation between the incidence of wound complications and infection after total hip arthroplasty and the use or nonuse of closed-suction drainage . The hip score and range of motion of the hip were unaffected by the use or nonuse of the drains . The cost of 1 set of hemovac drains is $ 135 and the cost for 4 - 5 dressings and bed sheet changes is about $ 50 . Although the hemovac is more expensive , the authors recommend the routine use of suction drains for wounds after primary total hip arthroplasty to reduce drainage , soaked dressings requiring reinforcement , ecchymosis and erythema around the wound , and psychological impact on the patient 's fear of bleeding A r and omized prospect i ve trial of a continuous vacuum system ( VariDyne ) and an intermittent spring type system ( Hemovac ) was conducted in 126 consecutive orthopedic surgical wounds between February 1988 and October 1988 in which postoperative suction drainage was required . Comparison between the two groups showed a statistically significant difference among total drainage removed by the vacuum units and wound drainage into the dressing following drain removal . Hip and knee arthroplasty patients receiving continuous vacuum suction experienced a greater average drainage volume and better wound healing than those receiving the spring-loaded device . Overall , all wounds which utilized continuous vacuum drained less serosanguinous or serous fluid than those wounds utilizing the intermittent system following drain removal . A clear advantage to using a continuous vacuum suction device over an intermittent spring-loaded device is seen with respect to hematoma evacuation , wound drainage , wound healing , and possible complications OBJECTIVE To study the efficacy of closed suction drainage in clean nonemergent surgical fracture fixation or bone grafting on the extremities or pelvis . DESIGN A prospect i ve r and omized trial . SETTING The orthopaedic trauma service of a Level I trauma hospital . PATIENTS Patients were older than age eighteen years and undergoing clean nonemergent surgical fracture fixation or bone grafting procedures on the extremities ( excluding h and s and feet ) or pelvis . INTERVENTION The application of a surgical drain . MAIN OUTCOME MEASUREMENTS Wound drainage , edema , hematoma and erythema , dehiscence , infection , and need for surgery or readmission were followed for six weeks . A univariate analysis with Student 's t test for continuous variables and chi-squared analysis for all categorical data were used , with a p value of < or = 0.05 considered statistically significant . RESULTS A total of 202 patients were r and omized to 102 patients with no drain and 100 patients with a drain . There was no significant difference between the groups with regard to injury severity , systemic disease , age , body weight , physical status , or estimated blood loss . There was no significant difference between the drain and no-drain groups in any of the parameters evaluated . CONCLUSION There is no significant difference between drained and nondrained wounds in clean , nonurgent orthopaedic trauma surgery . It appears that drainage systems can be safely eliminated in this group To evaluate the effectiveness of closed wound drainage in shoulder surgery , 300 patients were enrolled in a prospect i ve r and omized study . Three operations were studied : rotator cuff repair , anterior reconstruction for instability , and arthroplasty . One hundred patients were included in each group . All patients were evaluated for wound hematoma , infection , variation in postoperative rehabilitation caused by wound problems , and length of hospital stay . No statistical difference was found between the patients whose wounds were drained and those whose wounds were not drained . This finding existed within each category . Our data do not support the routine use of closed wound drainage in elective shoulder surgery Background The purpose of this prospect i ve study was to assess the impact of closed suction drainage on transfusion requirements , frequency of dressing changes , and wound healing following posterior spinal fusion in adolescents with idiopathic scoliosis . Methods Thirty patients were r and omly assigned to one of two groups : drain or no drain . Although the group with drains received more postoperative autologous blood transfusions than the group with no drains ( 0.88 vs 0.5 unit ) , the difference was not statistically significant ( P = 0.2131 ) . In the undrained group , 58 % of the patients had moderate to completely saturated dressings on the second postoperative day compared with only 17 % of patients in the drained group . Three of 12 patients in the undrained group demonstrated a wound complication rate compared with no complications in the drained group . Conclusion In conclusion , subcutaneous closed suction drainage can improve immediate postoperative wound care without significantly increasing blood loss and transfusion requirements for patients undergoing surgery for idiopathic scoliosis We prospect ively r and omized 415 total joint replacements for either a closed wound-drainage system or no postoperative drainage . Drainage was not used in 200 total joint replacements , of which 138 were total knee replacements and sixty-two , total hip replacements . Drainage was used in 215 total joint replacements , of which 137 were total knee replacements and seventy-eight , total hip replacements . All patients were evaluated for the presence of excessive postoperative drainage that necessitated cessation of the range-of-motion exercises , the amount of transfused blood ( homologous and autologous ) , and the preoperative and postoperative hemoglobin levels . The range of motion was assessed daily in the patients who had a total knee replacement . No statistical difference was found in the number of patients who had excessive postoperative drainage from a drained or non-drained wound . There was also no statistical difference with respect to the amount of transfused blood and the preoperative and postoperative hemoglobin levels . Furthermore , in the patients who had a total knee replacement , there were no statistical differences between drained and non-drained wounds with respect to the daily range of motion during the first seven days postoperatively . The mean amount of blood transfused was 157 milliliters in the total knee replacements with drains , 160 milliliters in the total knee replacements without drains , 188 milliliters in the total hip replacements with drains , and ninety-three milliliters in the total hip replacements without drains . ( ABSTRACT TRUNCATED AT 250 WORDS The use of closed suction drainage after spinal surgery remains controversial . The purpose of this study was to determine the indications for closed suction drainage after single-level lumbar surgery . Two hundred patients who were scheduled to undergo single-level lumbar surgery without fusion were prospect ively r and omized into two groups . One group had a closed wound suction drain placed deep to the lumbodorsal fascia before routine closure , whereas the second group had no drain placed . Hemostasis was achieved in all patients before the surgeon had knowledge of the r and omization outcome . All drains were removed on the 2nd postoperative day , and the amount of drainage was recorded . After surgery , the patients were evaluated for signs and symptoms of continued wound drainage , hematoma/seroma formation , and /or infection as well as evidence of an acquired neurologic deficit . One hundred three patients had a drain placed before closure and two patients developed postoperative wound infection , both of which were successfully treated with orally administered antibiotics . Of the 97 patients who had no drain placed after the surgical procedure , one patient developed a postoperative wound infection that was treated with surgical incision and drainage , as well as intravenously administered antibiotics . Statistical analysis revealed that the presence or absence of a drain did not affect the postoperative infection rate . No new neurologic deficits occurred in any postoperative patient . The use of drains in single-level lumbar laminectomy without fusion did not affect patient outcome . There was no significant difference in the rate of infection or wound healing and no patient developed a postoperative neurologic deficit Background Little data exist on the effect of routine use of postoperative drainage after arthroscopic anterior cruciate ligament reconstruction , although clinical studies of other procedures have not shown benefit to this practice . Hypothesis Use of a postoperative drain will not result in decreased suprapatellar girth , increased range of motion , and decreased pain compared with nonuse . Study Design Prospect i ve r and omized clinical trial . Methods Twenty-one patients undergoing arthroscopically assisted bone-patellar tendon-bone anterior cruciate ligament reconstruction were r and omly assigned to receive a drain for 24 hours ( 12 patients ) or no drain ( 9 patients ) . Data for comparison of groups were collected daily through postoperative day 7 . Results Pain scores on a visual analog scale demonstrated the same improving trend over time for both treatment and control groups ; however , the treatment group had significantly higher average pain scores , except on day 7 . Differences in suprapatellar girth , flexion , and extension were not found to be statistically significant between groups . Conclusion Use of a drain after arthroscopically assisted anterior cruciate ligament reconstruction provided no benefit in terms of range of motion , effusion , or pain in the early postoperative period We undertook a prospect i ve , r and omised study in order to evaluate the efficacy of clamping the drains after intra-articular injection of saline with 1:500 000 adrenaline compared with post-operative blood salvage in reducing blood loss in 212 total knee arthroplasties . The mean post-operative drained blood volume after drain clamping was 352.1 ml compared to 662.3 ml after blood salvage ( p < 0.0001 ) . Allogenic blood transfusion was needed in one patient in the drain group and for three in the blood salvage group . Drain clamping with intra-articular injection of saline with adrenaline is more effective than post-operative autologous blood transfusion in reducing blood loss during total knee arthroplasty We report on the results of a prospect i ve r and omised controlled trial to evaluate the use of an intra-articular drain following arthroscopically assisted ACL reconstruction using patellar tendon autograft . Forty-nine patients were recruited for the trial and r and omised into receiving or not receiving a drain following surgery . An independent observer who was blinded for the use of the drain assessed the knees for swelling , range of movement ( ROM ) and pain at 2 , 4 and 6 weeks postoperatively . Muscle strength was assessed at 12 weeks following surgery using the KIN COM III isometric dynamometer . We found that the knees that were drained following surgery initially had less swelling and a better ROM . However , at 4 weeks this difference had disappeared . At 3 and 6 months , there was no functional difference between the two groups . We recommend that no drain be used following ACL reconstruction as removal of the drain is uncomfortable and carries theoretical and avoidable risks The purpose of this study was to compare the costs and outcomes of the postoperative autoreinfusion device , the Constavac ™ , with the st and ard suction device , the Hemovac ™ , in which blood drainage is discarded , in patients undergoing total joint arthroplasty of the knee or hip . At the completion of the surgical procedure , a total of 91 subjects were r and omly assigned to one of the two device groups . The findings of this study , which included a limited homogeneous sample , do not support the use of the Constavac ™ device in patients undergoing total joint arthroplasty A prospect i ve study of 120 consecutive total hip replacements showed that deep suction drains produced maximal drainage volumes in the first 24 hours . Their continued presence result ed in minimal further drainage , did not reduce the likelihood of haematoma formation and led in some cases to the spread of skin organisms into the wound Ninety-six patients ( 63 females and 33 males ) who underwent total joint arthroplasty or spinal reconstructive surgery were r and omized to receive either a Solcotrans Plus or a Stryker-CBC ConstaVAC closed-wound drainage system . A binomial test showed that the Stryker-CBC ConstaVAC system was significantly preferred over the Solcotrans Plus system for ease of use , as reported by nurses . However , Solcotrans Plus was more cost-effective because a larger volume of blood shed by a patient could be reinfused while maintaining the st and ards of the American Association of Blood Banks . The difference in the occurrence of side effects between the two systems was not statistically significant Background No scientific study has addressed the effects of the routine use of postoperative drains in the donor site after arthroscopic anterior cruciate ligament reconstruction using hamstring tendons . Hypothesis Patients who have drains placed in their donor sites have less lower extremity edema , more motion , and more comfort in the early postoperative period . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods Thirty-four patients undergoing arthroscopically assisted quadruple hamstring tendon anterior cruciate ligament reconstruction were r and omly assigned to either receive a drain for 24 hours placed at the donor site ( 17 patients ) or have no drain at the donor site ( 17 patients ) . Data were collected on postoperative days 1 , 3 , 5 , and 7 regarding knee flexion , knee extension , thigh circumference , leg circumference , and visual analog scale ( measuring pain ) . Results In the study group versus the control group , there were increased knee flexion measurements on postoperative day 7 ( 84 ° vs 69 ° , P < . 05 ) ; smaller thigh circumference measurements on postoperative day 7 ( 36.8 vs 40.1 cm , P < . 05 ) ; smaller leg circumference measurements on postoperative days 3 ( 33.2 vs 36.4 cm , P < . 05 ) , 5 ( 32.7 vs 36.0 cm , P < . 05 ) , and 7 ( 31.8 vs 35.7 cm , P < . 001 ) ; and a lower visual analog scale score on postoperative days 3 ( 40.38 vs 57.50 , P = . 001 ) , 5 ( 38.46 vs 60.35 , P = . 001 ) , and 7 ( 38.07 vs 61.43 , P = . 001 ) . Conclusion Drain placement at the donor site after anterior cruciate ligament reconstruction gives more comfort to the patient and provides better flexion within the first week We prospect ively r and omised 100 patients undergoing cemented total knee replacement to receive either a single deep closed-suction drain or no drain . The total blood loss was significantly greater in those with a drain ( 568 ml versus 119 ml , p < 0.01 ; 95 % CI 360 to 520 ) although those without lost more blood into the dressings ( 55 ml versus 119 ml , p < 0.01 ; 95 % CI -70 to 10 ) . There was no statistical difference in the postoperative swelling or pain score , or in the incidence of pyrexia , ecchymosis , time at which flexion was regained or the need for manipulation , or in the incidence of infection at a minimum of five years after surgery in the two groups . We have been unable to provide evidence to support the use of a closed-suction drain in cemented knee arthroplasty . It merely interferes with mobilisation and complicates nursing . Reinfusion drains may , however , prove to be beneficial A prospect i ve investigation was design ed to determine the volume and the evolution of bleeding after closure of the surgical wound following knee arthroplasty , as well as the incidence of infection and bacterial contamination in relation with the time that the suction drain was left in place . The drain was removed either 12 , 24 or 48 hours after the operation . The presence of any signs of clinical infection was recorded . The tip of the drain , 1 cm of its subcutaneous portion and a sample from the collecting bottle were studied for bacterial contamination . In the 12-hr group , no microorganisms were isolated in cultures either from the tip , the subcutaneous portion or the bottle of the drain . In the 24-hr group , 87 % of the total postoperative bleeding was collected during the first 12 hours . In two cases , the sample s obtained from the tip and the subcutaneous portion of the drain were positive for Staphylococcus epidermidis . In the 48-hr group , 91 % and 97 % of the total bleeding volume was collected during the first 12 and 24 hours , respectively . In two cases , St. epidermidis was isolated in cultures from the subcutaneous portion of the drain . The clinical evaluation of wound healing was comparable in all three groups The efficacy of closed suction drains following joint arthroplasty operations was prospect ively evaluated in a r and omized manner . All 88 patients allotted to primary knee or hip arthroplasty operations during a 6-month period were included in the study . Drains were used in 32 of 58 patients following total knee arthroplasty and in 18 of 30 total hip arthroplasties . No statistical difference was found in the hemoglobin levels measured following surgery and in the number of patients requiring blood transfusions between the two groups after total hip arthroplasty ( P = .06 ) . The power of the test to detect a difference of 2 g% in hemoglobin levels is 94 % . Two patients from each group had a transient serous discharge for 3 to 4 days following surgery and none had wound infections . Significantly more blood transfusions were needed in patients with drains following total knee arthroplasty compared with patients without drains ( 0.7 unit per patient versus 0.2 unit per patient , P = .005 ) to maintain the same hemoglobin blood levels . Patients with no drains had significantly more transient sterile serous wound discharge than patients with drains ( 38.4 % vs 12.5 % , P = .02 ) . Superficial wound infection necessitating antimicrobial medication developed in one patient with drains and in no patients in the other group . These results suggest that drains may not be needed following total hip arthroplasty . The more common serous wound discharge may be of some concern when drains are not used following total knee arthroplasty Study Design . A prospect i ve r and omized study . Objectives . To study the risk of infection , hematoma , and neurologic deficits following extensive lumbar spine surgery in patients with or without prophylactic closed wound suction drain placement . Summary of Background Data . One r and omized study assessing prophylactic drain placement in one-level lumbar spine surgery suggested that the use of a wound drain is not effective at preventing infection and may actually increase the rate of this complication . Our study was design ed to determine the efficacy of closed wound suction drainage in preventing complications after extensive lumbar spine surgery . Methods . Eighty-three consecutive patients undergoing extensive lumbar spine surgery were prospect ively r and omized to one of two groups . Forty-two patients had a closed wound suction drain placed before wound closure and 41 patients did not have a drain placed . The two groups were then assessed for differences in postoperative infection rate , incidence of hematoma and neurologic deficits , operating room time , estimated blood loss , hemoglobin and hematocrit values , temperature , dressing drainage , and length of hospital stay . Results . No infections , epidural hematomas , or new neurologic deficits were encountered in either group of patients . The only significant finding was a higher temperature in the “ no drain ” group the first day after surgery ( P = 0.0437 ) . Conclusions . Based on the findings in this and other studies , the decision to use or not use a wound drain following lumbar spine surgery should be left to the surgeon ’s discretion We report the use of ultrasound in the assessment of the efficacy of wound drains in preventing wound haematoma . 171 patients with proximal femoral fractures who underwent AO dynamic hip screw or hemiarthroplasty were r and omized as to whether or not they should receive wound drainage . Patients then underwent ultrasound examination on the 5th postoperative day to localize and quantify any wound haematomas . Results show that drains are effective in preventing wound collection s , but only while in situ ; following the removal of drains the size of result ing wound collection s is the same whether the wound has been drained or not ( Student 's t-test ; t = 0.19 , NS ) . This study questions current theories on the mechanisms by which wound drainage is thought to influence wound healing We compared a novel external suction drainage ( ESD ) system with a conventional internal suction drainage ( ISD ) system in patients undergoing primary total hip or knee arthroplasties . Forty-two consecutive patients were studied : 22 who received an ISD system and 20 who received the ESD system . Drainage volume was measured , st and ardized question naires were used to assess patient comfort and response to drain removal , and number of complications were recorded . Significantly less drainage , less pain , and fewer complications occurred in patients treated with the ESD system ( P<.05 for each endpoint ) . Results showed that ESD has advantages over ISD in primary total hip and knee arthroplasties One hundred thirty-six primary total knee arthroplasty patients were r and omized for the use of closed-suction , nonreinfusable wound drains . Blood loss was identical in the drained and undrained groups . Forty percent of undrained wounds compared with 0 % of drained wounds required dressing reinforcement . Sixty-nine percent of undrained wounds compared with 39 % of drained wounds developed ecchymosis , measuring 92 cm2 in the undrained group and 28 cm2 in the drained group . This study concludes that a simple wound drain effectively minimizes the undesirable accumulation of blood in the surrounding soft tissues and the postoperative wound dressing after total knee arthroplasty In a prospect i ve r and omised trial we evaluated the use of a post-operative closed-suction drain in unicompartmental knee replacement ( UKR ) . Seventy-eight patients were divided into two groups : one without a post-operative closed-suction drain ( Group A ) and one with a drain ( Group B ) . Both groups were matched for age , sex and pre-operative haemoglobin . In group A we observed a lower day one post-operative analgesic requirement , smaller knee circumference 3 days post-operatively and less local wound complications . Drain usage in UKR result ed in no significant advantage in post-operative pain , range of motion and hospital stay . Post-operative drainage does , however , increase the cost of the procedure both in labour and equipment expenditure . No deep infections occurred in either group during the follow-up period . We conclude that avoiding post-operative closed-suction drainage in UKR does not influence the outcome OBJECTIVES The purpose of this prospect i ve r and omised study was to examine whether routine drainage in surgery for traumatic hip fractures is useful . BASIC PROCEDURES At the end of surgery for hip fractures , 200 consecutive patients ( 51 men , 149 women ) were r and omised to receive suction drainage or not . The status of wound healing was evaluated , with specific reference to haematoma formation or wound infection . Indices of blood loss were the average blood loss during operation , a decrease in the haemoglobin level , fluid collected by the drain , and blood transfusion . MAIN FINDINGS The severity of wound haematoma and the number of wound infections was not significantly different between the two groups . The average blood loss during operation was 172 ml in the drainage group and 179 ml in the non-drainage group . The volume of drainage fluid was 146 ml . The haemoglobin concentration decreased by 1.4 mg/dl in the drainage group and by 1.3 mg/dl in the non-drainage group ( P = 0.83 ) . During admission , 55 patients in the drainage group received 2.5 units of blood and 50 patients in the non-drainage group received 2.7 units . CONCLUSIONS The severity of wound haematoma does not lead to statistically significant differences in wound infection rate . The routine use of suction drains may not prevent wound infections BACKGROUND The purpose of this study was to determine the utility of closed suction drainage ( CSD ) in elective total hip arthroplasty ( THA ) . PATIENTS AND METHODS We r and omized 104 elective , consecutive THAs to receive drainage ( 53 ) or no drainage ( 51 ) . 60 arthroplasties were cemented and 44 hybrid . RESULTS In the drainage group , 2 hematomas and 2 superficial wound infections occurred ; there were no wound complications in the undrained group ( p = 0.04 ) . Patients receiving drainage had a greater reduction in hematocrit ( 10.4 vs 7.4 ) ( p = 0.03 ) , and longer hospital stay ( 5.1 days vs 4.7 ) ( p = 0.01 ) . At the 3-month follow-up , we found no deep wound infections in either group . INTERPRETATION We no longer use CSD in elective , primary , routine THA There is no firm published evidence to support the use of closed suction drains . Over 20 years ago , large studies by the Public Health Laboratory Service and the National Research Council found that drains were risk factors for wound infection . A prospect i ve r and omised study of the use of closed suction drains after surgery for fractured neck of femur in 70 patients failed to show that drains improved wound healing . Drained cases had more complications |
1,623 | 18,212,524 | Results : Infa rct size was the major determinant of the development of life-threatening edema .
Other associated determinants were early mass effect , involvement of other vascular territories , higher body temperature , internal carotid artery occlusion , and need for mechanical ventilation .
However , predictive values were only moderate .
Conclusions : The size of the ischemic area is the major determinant .
Single predictors lack sufficient predictive value to select c and i date s for surgical decompression before the onset of clinical signs of herniation | Background : We performed a systematic review to identify predictors of the development of life-threatening brain edema in patients with middle cerebral artery infa rct ion . | Background and Purpose — Transcranial color-coded duplex sonography ( TCCS ) allows bedside imaging of intracranial hemodynamics and parenchymal structures . It provides reliable information regarding midline shift ( MLS ) in space-occupying hemispheric stroke . We studied the value of MLS measurement to predict fatal outcome at different time points after stroke onset . Methods — Forty-two patients with acute , severe hemispheric stroke were enrolled . Cranial computed tomography ( CCT ) and extracranial duplex sonography were performed on admission . TCCS was carried out 8±3 , 16±3 , 24±3 , 32±3 , and 40±3 hours after stroke onset . Lesion size was determined from follow-up CCT . Results — Twelve patients died as the result of cerebral herniation ( group 1 ) ; 28 survived ( group 2 ) . Two patients received decompressive hemicraniectomy and were therefore excluded from further evaluation . MLS was significantly higher in group 1 as early as 16 hours after onset of stroke . Specificity and positive predictive values for death caused by cerebral herniation of MLS ≥2.5 , 3.5 , 4.0 , and 5.0 mm after 16 , 24 , 32 , and 40 hours were 1.0 . Conclusions — TCCS helps to estimate outcome as early as 16 hours after stroke onset and thus facilitates identification of patients who are unlikely to survive without decompressive craniectomy . Because of its noninvasive character and bedside suitability , sonographic monitoring of MLS might be a useful tool in management of critically ill patients who can not undergo repeated CCT scans BACKGROUND AND PURPOSE Malignant , space-occupying supratentorial ischemic stroke is characterized by a mortality rate of up to 80 % . Several reports indicate a beneficial effect of hemicraniectomy in this situation . However , whether and when decompressive surgery is indicated in these patients is still a matter of debate . METHODS In an open , prospect i ve trial we performed hemicraniectomy in 63 patients with acute complete middle cerebral artery infa rct ion . Initial clinical presentation was assessed by the Sc and inavian Stroke Scale ( SSS ) and the Glasgow Coma Scale ( GCS ) . All survivors were reexamined 3 months after surgical decompression , with the clinical evaluation grade d according to the Rankin Scale ( RS ) and Barthel Index ( BI ) . We analyzed the influence of early decompressive surgery ( < 24 hours after symptom onset , based on clinical status at admission and initial CT findings ) versus late surgery ( > 24 hours after first reversible signs of herniation ) on mortality , functional outcome , and the length of time of critical care therapy was needed . RESULTS In total , 46 patients ( 73 % ) survived . Despite complete hemispheric infa rct ion , no survivor suffered from complete hemiplegia or was permanently wheelchair bound . In patients with speech-dominant hemispheric infa rct ion ( n=11 ) , only mild to moderate aphasia was present . The mean BI score was 65 , and RS score revealed severe h and icap in 13 % of the patients . In 31 patients with early decompressive surgery , mortality was 16 % and BI score 68.8 . Early hemicraniectomy led to a significant reduction in the length of time critical care therapy was needed ( 7.4 versus 13.3 days , P<0.05 ) . CONCLUSIONS In general , the outcome of patients treated with craniectomy in severe ischemic hemispheric infa rct ion was surprisingly good . In addition , early decompressive surgery may further improve outcome in these patients BACKGROUND AND PURPOSE Early identification of acute stroke patients at risk of fatal brain swelling is necessary to facilitate implementation of aggressive therapies . Initial clinical , laboratory , and CT characteristics that may be used as selection criteria were analyzed to determine predictors of herniation and neurological death . METHODS Data from the placebo arm of the Lubeluzole-International-9 trial were review ed to identify patients with fatal brain edema . Early clinical , laboratory , and radiographic parameters were evaluated in a case-control design . Initial CT scans were analyzed for early ischemic abnormalities by 2 blinded investigators . RESULTS Twenty-three patients died from brain swelling , with minimum baseline National Institutes of Health Stroke Scale ( NIHSS ) scores of 20 ( n=12 ; mean , 23.2+/-1.8 ) with left and 15 ( n=11 ; mean , 17.6+/-2.2 ) with right hemispheric infa rct ions ( P=0 . 0001 ) . A sample of 112 subjects with comparably severe strokes , but who did not die from brain swelling , was selected from the remaining population according to the same NIHSS scores . Among clinical and laboratory characteristics , nausea/vomiting within 24 hours after onset ( odds ratio [ OR ] , 5.1 ; 95 % CI , 1.7 to 15.3 ; P=0.003 ) and 12-hour systolic blood pressure > /=180 mm Hg ( OR , 4.2 ; 95 % CI , 1.4 to 12.9 ; P=0.01 ) were independently associated with fatal brain swelling . Among radiographic factors , only hypodensity of > 50 % of the middle cerebral artery territory on initial CT scan was an independent predictor ( OR , 6.1 ; 95 % CI , 2.3 to 16.6 ; P=0.0004 ) . CONCLUSIONS Patients with baseline NIHSS score > /=20 with left or > /=15 with right hemispheric infa rct ions within 6 hours of symptom onset who also have nausea/vomiting or > 50 % middle cerebral artery territory hypodensity are at high risk for developing fatal brain swelling BACKGROUND AND PURPOSE To predict malignant course in patients with large middle cerebral artery ( MCA ) infa rct ion , we combined PET imaging and neuromonitoring , including microdialysis . METHODS Thirty-four patients with stroke of > 50 % of the MCA territory in early cerebral CT scan were included . Probes for microdialysis and measurement of intracranial pressure and tissue oxygen pressure ( Pto2 ) were placed into the ipsilateral frontal lobe . PET was performed with 11C-flumazenil to assess CBF and irreversible neuronal damage . RESULTS PET measurements within 24 hours after stroke showed larger volumes of ischemic core ( mean , 144.5 versus 62.2 cm3 ) and larger volumes of irreversible neuronal damage ( 157.9 versus 47.0 cm3 ) in patients with malignant course ( ie , edema formation with midline shift ) than in patients with benign course . Mean cerebral blood flow values within the ischemic core were significantly lower and the volume of the ischemic penumbra was smaller in the malignant than in the benign group . In patients with malignant course , cerebral perfusion pressure dropped to < 50 to 60 mm Hg 22 to 72 hours ( mean , 52.0 hours ) after onset of symptoms ; subsequently , Pto2 dropped and glutamate increased , indicating secondary ischemia . Maximal changes in the monitored variables reached significant levels for glutamate , aspartate , GABA , glycerol , lactate-to-pyruvate ratio , hypoxanthine , intracranial pressure , cerebral perfusion pressure , and Pto2 . CONCLUSIONS PET allowed prediction of malignant MCA infa rct ion within the time window suggested for hemicraniectomy . Neuromonitoring helped to classify the clinical courses by characterizing pathophysiological sequelae of malignant edema formation . In contrast to PET , however , it did not predict fatal outcome early enough for successful implementation of invasive therapies BACKGROUND In laboratory animals , cerebral ischaemia is worsened by hyperthermia and improved by hypothermia . Whether these observations apply to human beings with stroke is unknown . We therefore examined the relation between body temperature on admission with acute stroke and various indices of stroke severity and outcome . METHODS In a prospect i ve and consecutive study 390 stroke patients were admitted to hospital within 6 h after stroke ( median 2.4 h ) . We determined body temperature on admission , initial stroke severity , infa rct size , mortality , and outcome in survivors . Stroke severity was measured on admission , weekly , and at discharge on the Sc and inavian Stroke Scale ( SSS ) . Infa rct size was determined by computed tomography . Multiple logistic and linear regression outcome analyses included relevant confounders and potential predictors such as age , gender , stroke severity on admission , body temperature , infections , leucocytosis , diabetes , hypertension , atrial fibrillation , ischaemic heart disease , smoking previous stroke , and comorbidity . FINDINGS Mortality was lower and outcome better in patients with mild hypothermia on admission ; both were worse in patients with hyperthermia . Body temperature was independently related to initial stroke severity ( p < 0.009 ) , infa rct size ( p < 0.0001 ) , mortality ( p < 0.02 ) , and outcome in survivors ( SSS at discharge ) ( p < 0.003 ) . For each 1 degrees C increase in body temperature the relative risk of poor outcome ( death or SSS score on discharge < 30 points ) rose by 2.2 ( 95 % CI 1.4 - 3.5 ) ( p < 0.002 ) . INTERPRETATION We have shown that , in acute human stroke , an association exists between body temperature and initial stroke severity , infa rct size , mortality , and outcome . Only intervention trials of hypothermic treatment can prove whether this relation is causal Analysis of early deaths after stroke is important , since some deaths may be preventable . Previous studies have relied on retrospective and often incomplete clinical data , for comparison with pathological findings . The present study is based on 1073 consecutive stroke patients admitted to an intensive care stroke unit from a well-defined population . There were 212 deaths within the first 30 days , yielding a mortality rate of 20 % . Clinical , radiological , and laboratory data were collected prospect ively according to a st and ardized protocol . Autopsies were performed on 90 of the 212 patients , and CT scanning on a further 27 . Early mortality after stroke exhibits a bimodal distribution . One peak occurs during the first week , and a second during the second and third weeks . The majority of deaths in the first week are due to transtentorial herniation . Of these , deaths due to hemorrhage usually occur within the first three days , whilst deaths due to infa rct ion peak between the third and sixth day post ictus . After the first week , deaths due to relative immobility ( pneumonia , pulmonary embolism and sepsis ) predominate , peaking towards the end of the second week . Cardiac deaths occur throughout the first month , and unfortunately account for many deaths in patients with small functional deficits . Stroke VOL 15 , No 3 , BACKGROUND AND PURPOSE No neuroradiological markers have been characterized that support a timely decision for decompressive surgery in malignant middle cerebral artery ( MCA ) infa rct ion ( mMCAI ) . This case-control study was design ed to analyze whether early cerebral CT ( CCT ) scanning provides reliable information for the prospect i ve selection of stroke patients at risk of developing mMCAI . METHODS Thirty-one pairs ( n=62 ) were formed with cases ( mMCAI ) and controls ( acute but not malignant MCA infa rct ion ) closely matched in terms of age , sex , and stroke etiology . CCT was performed within 18 hours of stroke onset and analyzed by a blinded neuroradiologist according to a defined panel of 12 CCT criteria . RESULTS In terms of predicting mMCAI , the criteria of extended MCA territory hypodensities > 67 % and > 50 % , hemispheric brain swelling , midline shift , and hyperdense MCA sign exhibited high specificity ( 100 % , 93 . 5 % , 100 % , 96.7 % , and 83.9 % , respectively ) but low sensitivity ( 45.2 % , 58.1 % , 12.9 % , 19.4 % , and 70.9 % , respectively ) . Two criteria yielded high sensitivity ( subarachnoid space compressed , 100 % ; cella media compressed , 80.6 % ) but low specificity ( 29 % and 74.2 % , respectively ) . The criterion of attenuated corticomedullary contrast yielded both high specificity ( 96.8 % ) and sensitivity ( 87.1 % ) . The latter remained as the crucial criterion [ Exp(B)=90.8 ; 95 % CI , 5.8 to 1427 . 5 ] in a 2-tailed logistic regression analysis with the strongest correlating parameters ( Spearman correlation factor > /=0.6 or < /=-0.6 ) . CONCLUSIONS The analysis of CCT scans within 18 hours of stroke onset revealed an attenuated corticomedullary contrast as the crucial CCT criterion , which , with both sufficient sensitivity and specificity , predicted mMCAI with 95 % certainty Background and Purpose — Cerebral venous pressure is governed by intracranial pressure , cerebral perfusion pressure , and venous outflow resistance . Therefore , changes in venous flow velocities are to be expected because of changes in intracranial pressure and brain tissue dislocation in patients with ischemic stroke and space-occupying brain edema . Methods — In 21 prospect ively recruited patients with middle cerebral artery stroke and postischemic edema , flow velocities in the basal veins , the vein of Galen , the straight sinus , and the P2 segment of the posterior cerebral artery were recorded every 0.9±0.5 days during the first 5 days after symptom onset with the use of transcranial color-coded duplex sonography . The midline shift of the third ventricle was determined by B-mode imaging . Results — We observed an initial increase of flow velocity in the basal vein ipsilateral to the lesion , followed by a significant decrease within 5 days after symptom onset and with increasing midline shift in patients with brain herniation . In the straight sinus , flow velocity showed a biphasic U-shaped response to increasing dislocation of the third ventricle , with an initial decrease followed by an increase in the course of mass movement ( midline shift 1 to 1.5 cm ) . A steep increase of flow velocity in the vein of Galen took place with a midline shift > 1.5 cm . In the survivors these changes could not be observed . Flow velocity in the P2 segment of the posterior cerebral artery followed a typical course in neither the fatal cases nor the survivors . Conclusions A— Monitoring of flow velocities in the basal cerebral veins and in the straight sinus can provide additional pathophysiological information in patients with space-occupying brain edema after acute stroke PURPOSE To investigate the incidence and prognostic value of local brain swelling , the extent of parenchymal hypodensity , and the hyperdense middle cerebral artery sign as shown by CT within the first 5 hours after the onset of symptoms in patients with angiographically proved middle cerebral artery trunk occlusions . METHODS Fifty-three patients were studied prospect ively with CT 46 to 292 minutes ( median , 120 ; mean , 134 + /- 59 ) after symptom onset and scored clinical ly at admission and 4 weeks later . All patients were treated with recombinant tissue plasminogen activator ( 30 to 100 mg ) . RESULTS Early CT showed parenchymal hypodensity in 43 patients ( 81 % ) , local brain swelling in 20 patients ( 38 % ) , and hyperdensity of the middle cerebral artery trunk in 25 patients ( 47 % ) . Hypodensity covering more than 50 % of the middle cerebral artery territory had an 85 % , local brain swelling a 70 % , and the hyperdense middle cerebral artery sign a 32 % positive predictive value for fatal clinical outcome . Specificity of these findings for fatal outcome was 94 % , 83 % , and 51 % , respectively , and sensitivity was 61 % , 78 % and 44 % , respectively . CONCLUSIONS Early CT in acute middle cerebral artery trunk occlusion is highly predictive for fatal clinical outcome if there is extended hypodensity or local brain swelling despite aggressive therapeutic attempts such as thrombolysis or decompressive surgery BACKGROUND AND PURPOSE We sought to study the prognostic value of early 99mtechnetium-ethyl-cysteinate-dimer single-photon emission CT ( 99mTc-ECD SPECT ) for fatal ischemic brain edema in patients with middle cerebral artery ( MCA ) stroke compared with the prognostic value of CT and of clinical findings . METHODS We prospect ively studied 108 patients clinical ly , with 99mTc-ECD SPECT , and with CT within 6 hours of symptom onset ( Sc and inavian Stroke Scale < 40 points ) appropriate to MCA ischemia . The follow-up consisted of Sc and inavian Stroke Scale and CT on days 1 and 7 , Barthel Index , and Modified Rankin Scale after 3 months . An activity deficit of the complete MCA territory on the SPECT scans and a parenchymal hypoattenuation of the complete MCA territory on CT scans were considered as predictors for a fatal MCA infa rct ion due to mass effect and midbrain herniation . RESULTS In 11 of 108 patients ( 10 % ) , the MCA infa rct ion was the cause of death . The sensitivity of SPECT for fatal outcome was 82 % in both visual and semiquantitative analyses , while specificity was 98 % and 99 % , respectively . The sensitivity and specificity of baseline CT were 36 % and 100 % , respectively ; the sensitivity and specificity of clinical findings ( Sc and inavian Stroke Scale , depressed level of consciousness , gaze deviation ) varied from 36 % to 73 % and from 45 % to 88 % , respectively . In a multivariate logistic regression model , only SPECT findings were found to be independent predictors of malignant MCA infa rct ion/death . CONCLUSIONS We were able to identify patients with fatal MCA infa rct ion with high accuracy by using 99mTc-ECD SPECT within 6 hours of stroke onset . This technique offers great potential to select stroke patients for specific therapies , eg , decompressive hemicraniectomy , soon after onset of symptoms Abstract Objective : To find what the mortality rate of space-occupying ( ‘ malignant ’ ) middle cerebral artery ( MCA ) infa rct ion is under maximum conservative intensive care . To establish whether any early indicators of survival exist . Design : Prospect i ve descriptive study . Setting : Neuro-critical care unit of a university hospital . Patients : Fifty-three patients ( mean age 64 ± 10 years ) with ‘ malignant ’ MCA infa rct ion . Interventions : Maximum conservative intensive care using a st and ardized protocol ( heparin , osmotherapy , tromethamol , mild hyperventilation ) . The start of therapy was within 12 h after the onset of symptoms . Measurements and results : The Glasgow Coma Scale ( GCS ) and Sc and inavian Stroke Scale ( SSS ) were recorded daily . A computed tomography ( CT ) scan was performed on admission , on day 3 and on day 7 . SSS , Barthel Index and Rankin Scale of the surviving patients were recorded after 3 months . On admission , the mean GCS was 13 ± 3 points and mean SSS 18 ± 7 points . All patients had to undergo mechanical ventilation ( 23 ± 26 h after the onset of symptoms ) and were comatose after 28 ± 30 h. Of 53 patients , 37 ( 70 % ) suffered brain death in the intensive care unit ( ICU ) after an average of 90 ± 59 h. After 3 months 42/53 ( 79 % ) patients had died . The Barthel Index of the surviving patients was 54 ± 12 points , the SSS 25 ± 9 points and the Rankin Scale 3 ± 1 points . The deceased patients had a significantly higher body temperature on admission than the surviving patients ( 36.8 ° C vs 36.3 ° C ) . Conclusions : The mortality of patients with ‘ malignant ’ MCA infa rct ion is very high despite maximum conservative intensive care BACKGROUND Although the clinical features of space-occupying ischemic stroke are well known , there are limited prospect i ve data on the clinical course of complete middle cerebral artery territory infa rct ion and on the predisposing factors leading to subsequent herniation and brain death . METHODS The clinical course of patients with complete middle cerebral artery territory infa rct ion , defined by computed tomography and vascular imaging , was evaluated . Initial clinical presentation was assessed by the Sc and inavian Stroke Scale and the Glasgow Coma Scale . Serial computed tomography with measurement of midline and septum pellucidum shift and data on the presence and location of vascular occlusion by angiography or Doppler ultrasound were obtained directly after admission . Time course and outcome were analyzed with regard to the clinical findings on admission and at follow-up . The functional status of surviving patients was assessed using the Barthel Index . RESULTS Fifty-five patients with complete middle cerebral artery territory infa rct ion caused by occlusion of either the distal intracranial carotid artery or the proximal middle cerebral artery trunk were studied . In all patients , embolic infa rct ion was presumed . The mean Sc and inavian Stroke Scale score on admission was 20 , and the time course of deterioration varied between 2 and 5 days . Forty-nine patients required ventilator assistance during the acute stage of disease . Only 12 patients ( 22 % ) survived the infa rct . The cause of death was transtentorial herniation with subsequent brain death in 43 patients . Survivors had a mean Barthel Index score of 60 ( range , 45 to 70 ) . CONCLUSIONS The prognosis of complete middle cerebral artery territory stroke is very poor and can be estimated by early clinical and neuroradiological data within the first few hours after the onset of symptoms . A space-occupying mass effect develops rapidly and predictably over the initial 5 days after presentation . Herniation occurred as an end point in 43 ( 78 % ) of these patients |
1,624 | 25,875,810 | The findings of this study will assist clinicians who seek to utilise suitable and accurate measures to assess upper limb function for a patient with neck pain . | Background Upper limb disability is a common musculoskeletal condition frequently associated with neck pain .
Recent literature has reported the need to utilise vali date d upper limb outcome measures in the assessment and management of patients with neck pain .
However , there is a lack of clear guidance about the suitability of available measures , which may impede utilisation .
This review will identify all available measures of upper limb function developed for use in neck pain patients and evaluate their measurement and practical properties in order to identify those measures that are most appropriate for use in clinical practice and research . | Study Design . Prospect i ve cohort study . Objective . To evaluate whether the DASH is not only a valid and responsive instrument to measure patients with shoulder , arm , and h and complaints , but also to evaluate patients with neck complaints . Summary of Background Data . The DASH has shown to be a valid and responsive question naire to evaluate disability in patients with shoulder , arm , and h and complaints . However , patients with shoulder , arm , or h and complaints frequently report neck complaints as well . Therefore , a valid and responsive question naire design ed for the whole upper extremity , including the neck , would be very useful and practical in upper-extremity research . Methods . Six hundred seventy-nine patients visiting their general practitioner with a new episode of nontraumatic complaints of the neck and upper extremity were evaluated by use of question naires at baseline and at 6-months follow-up . Six (sub)groups were formulated according to the location of complaints , including a subgroup with complaints in the shoulder-arm-h and region only and a group with complaints of the neck only . Disability ( DASH ) , general health [ SF-12 ( physical and mental component ) ] , severity , and persistence of complaints were assessed . Construct validity , floor and ceiling effects , and responsiveness were studied . Results . Correlations between the DASH and the other measures within the 6 (sub)groups at baseline ( construct validity ) , for the change scores at 6-months follow-up ( responsiveness ) , and the responsiveness ratios were classified as acceptable . No floor and ceiling effects were found . Conclusion . The DASH performed well with regard to the a priori hypotheses . This study has shown acceptable validity and responsiveness of the DASH for use in patients with nontraumatic neck complaints in addition to shoulder , arm , and h and complaints . We would caution against using the DASH in patients with neck complaints only , since fewer of the hypotheses could be confirmed in this subgroup Study Design . An observational prospect i ve cohort study in general practice . Objectives . To describe the clinical course and to identify predictors of recovery , changes in pain intensity , and changes in functional disability in patients with neck or shoulder symptoms at 3- and 12-month follow-up . Summary of Background Data . Knowledge on the clinical course and predictors of outcome in neck and shoulder symptoms is limited . Such knowledge would facilitate treatment decisions and may help to inform patients about their prognosis . Methods . Four hundred and forty-three patients who consulted their general practitioner with neck or shoulder symptoms participated in the study . Baseline scores of pain and disability , symptom characteristics , sociodemographic and psychological factors , social support , physical activity , general health , and comorbidity were investigated as possible predictors of recovery , changes in pain intensity , and changes in functional disability using multiple regression analyses . Results . The recovery rate was low ; 24 % of the patients reported recovery at 3 months and 32 % reported recovery at 12-month follow-up . Duration of the symptoms before consulting the GP and a history of neck or shoulder symptoms increased the probability of an unfavorable outcome . Furthermore , less vitality and more worrying were consistently associated with poorer outcome after 3 and 12 months . The area under the receiver-operator characteristic curve for the model predicting recovery was 0.8 at 3 months and 0.75 at 12 months . The explained variance of the models on pain and functional disability ranged from 43 to 54 % . Conclusions . The results found in this study indicate that besides clinical characteristics , psychological factors also predict the outcome of neck and shoulder symptoms Objectives For the measurement of patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 % , precision 4.4 % ) . The precise search filter had a sensitivity of 93.1 % and a precision of 9.4 % . Both filters performed very well in the validation sets . Conclusion The use of these search filters will contribute to evidence -based selection of measurement instruments in all medical fields OBJECTIVE To determine the prevalence , interrelation , and impact of musculoskeletal disorders of the upper limb in the general population . METHODS A total of 9,696 r and omly selected adults of working age were surveyed in a 2-stage cross-sectional study involving a screening question naire and a st and ardized physical examination in symptomatic subjects . Age- and sex-specific prevalence rates were estimated for several musculoskeletal disorders and for nonspecific pain in the upper limbs . The overlap and impact on daily activities and healthcare utilization were explored . RESULTS Among 6,038 first-stage responders , 3,152 reported upper limb symptoms and 1,960 were subsequently examined . Of subjects with pain , 44.8 % had 1 or more specific soft-tissue disorders . Site-specific prevalence rates were as follows : shoulder tendinitis 4.5 % among men and 6.1 % among women ; adhesive capsulitis 8.2 % among men and 10.1 % among women ; lateral epicondylitis 1.3 % among men and 1.1 % among women ; de Quervain 's disease 0.5 % among men and 1.3 % among women ; other tenosynovitis of the h and or wrist , 1.1 % among men and 2.2 % among women . Specific disorders tended to cluster ( P < 0.001 ) in individuals , with particular overlap at the shoulder . Compared with subjects with nonspecific pain , those with specific disorders more often reported inability to perform everyday tasks ( P < 0.05 ) , consultation with a doctor ( P < 0.05 ) , and use of prescribed medication ( P < 0.05 ) . CONCLUSION Upper limb pain is common in the general population and is often associated with physical signs suggestive of specific upper-limb disorders . These disorders have a substantial impact on physical function and use of health care Background : Epidemiological research in the field of soft tissue neck and upper limb disorders has been hampered by the lack of an agreed system of diagnostic classification . In 1997 , a United Kingdom workshop agreed consensus definitions for nine of these conditions . From these criteria , an examination schedule was developed and vali date d in a hospital setting . Objective : To investigate the reliability of this schedule in the general population . Methods : Ninety seven adults of working age reporting recent neck or upper limb symptoms were invited to attend for clinical examination consisting of inspection and palpation of the upper limbs , measurement of active and passive ranges of motion , and clinical provocation tests . A doctor and a trained research nurse examined each patient separately , in r and om order and blinded to each other 's findings . Results : Between observer repeatability of the schedule was generally good , with a median κ coefficient of 0.66 ( range 0.21 to 0.93 ) for each of the specific diagnoses considered . Conclusion : As expected , the repeatability of tests is poorer in the general population than in the hospital clinic , but the Southampton examination schedule is sufficiently reproducible for epidemiological research in the general population Study Design . A prospect i ve , multicenter , cross-sectional analysis of data from the National Spine Network data base . Objectives . To compare the relative impact of radicular and axial symptoms associated with disease of the cervical spine on general health as measured by the SF-36 Health Survey , and to compare the impact of these symptoms among patients of varying age and symptom duration . Background . Degenerative disorders of the cervical spine can cause debilitating symptoms of neck and arm pain . Physicians generally treat radiculopathy more aggressively than axial neck pain alone , although it has never been shown that the presence of radiculopathy leads to a greater impairment of physical and mental function . Material s and Methods . SF-36 Health Survey data were collected from all consenting patients seen within the National Spine Network . Patients with symptoms referable to the cervical spine ( as per their physician ) were included ( n = 1,809 ) . SF-36 scores for all eight scales ( bodily pain ( BP ) , vitality ( VT ) , general health ( GH ) , mental health ( MH ) , physical function ( PF ) , role physical ( RP ) , role emotional ( RE ) , and social function ( SF ) , and two summary scales ( Physical Component Summary [ PCS ] and Mental Component Summary [ MCS ] ) were calculated . Age/gender normative scores were subtracted from the scale scores to produce a negative “ impact ” score , which reflected how far below normal health status these patients were . Patients were grouped according to location of symptoms ( axial only , radicular only , or axial and radicular ) , age ( younger than 40 , 40 to 60 , and older than 60 years ) , and symptom duration ( acute : < 6 wk ; subacute : 6 wk–6 mo ; and chronic : > 6 mo ) . SF-36 scores were compared between all groups using analysis of variance and multiple comparisons with Bonferroni adjustment . Results . Patients who presented with both axial and radicular symptoms had the lowest SF-36 scores relative to age and gender norms . These scores were significantly lower than those for patients with only axial or only radicular symptoms across all eight subscales ( P < 0.05–P < 0.0001 ) . Scores for patients with only axial pain were significantly lower than for patients with only radicular pain for VT ( P < 0.04 ) and GH ( P < 0.004 ) . Patients younger than 40 and those between ages 40 to 60 years were significantly more impacted by their symptoms than patients older than 60 years for all eight scales ( P < 0.01 ) . PCS scores were similar for acute , subacute , and chronic groups , whereas MCS scores were significantly worse for patients with chronic pain . Conclusions . Combined neck and arm pain were much more disabling than either symptom alone . Younger patients ( younger than 40 or 40–60 ) were more affected by these symptoms than patients older than 60 years . In addition , as symptom duration increased , a negative impact on mental health was observed , although chronic symptoms did not affect physical health . This study suggests that patients with a significant component of axial pain in conjunction with cervical radiculopathy should be considered the most affected of all patients with cervical spondylosis . Given the evidence that the treatment methods at the disposal of physicians are effective , this study suggests that prompt treatment of these patients may help avoid the harmful effects of chronic symptoms on mental functioning , especially among younger patients who were found to be more impacted by the symptoms |
1,625 | 24,487,151 | Compared with SG , RYGB had significantly better effect in resolving type 2 diabetes mellitus , hypertension , hypercholesterolemia , gastroesophageal reflux disease , and arthritis .
However , RYGB had higher incidence of complications and reoperation , and longer operation time than SG .
RYGB was more effective than SG in the resolution of obesity-related comorbidities , SG was a safer procedure with a reduced rate of complications and reoperation | PURPOSE Roux-en-Y gastric bypass ( RYGB ) and sleeve gastrectomy ( SG ) are 2 of the most widely used bariatric procedures today , in this meta- analysis , both techniques were compared for evaluating the efficacy and safety of the treatment of morbid obesity . | Objective : To present long-term results of a large series of patients su bmi tted to laparoscopic Roux-en-Y gastric bypass ( RYGBP ) for morbid obesity . Background : Reports on long-term results of RYGBP are scarce and focus primarily on weight loss . Our aim is to provide mid- to long-term data of RYGBP , with detailed results on weight loss , evolution of comorbidities and quality of life , also using the BAROS score . Methods : All patients who underwent a primary RYGBP for morbid obesity in our 2 hospitals between 1999 and August 2008 were included . Data were collected prospect ively in a computerized data base , and review ed for the purpose of this study . Results : A total of 379 patients were included in the analysis of long-term results , 282 women , and 97 men , with a mean BMI of 46.3 kg/m2 . After 5 years , 74.9 % of the patients achieved an excess weight loss of at least 50 % , with a mean of 62.7 % and 76.8 % achieved a BMI < 35 kg/m2 . The corresponding figures after 7 years were 64.9 , 58.1 , and 71.9 , respectively . There was a small but significant long-term weight regain . All comorbidities improved markedly in the vast majority of patients , with no significant difference between the 3- and 5-year terms . Quality of life also improved markedly , and more than 95 % of the patients had a good to excellent 5-year overall result according to the BAROS score . Conclusions : Laparoscopic RYGBP for morbid obesity results in good and maintained weight loss up to 7 years in the majority of patients , improves quality of life and markedly improves all the evaluated comorbidities , result ing in good to excellent overall 5-year results in 97 % of the patients according to the BAROS score Background Aim ing to clarify the mechanism of weight loss after the restrictive bariatric procedure of sleeve gastrectomy ( LSG ) , the volumes and pressures of the stomach , of the removed part , and of the remaining sleeve were measured in 20 morbidly obese patients . Methods The technique used consisted of occlusion of the pylorus with a laparoscopic clamp and of the gastroesophageal junction with a special orogastric tube connected to a manometer . Instillation of methylene-blue-colored saline via the tube was continued until the intraluminal pressure increased sharply , or the inflated stomach reached 2,000 cc . After recording of measurements , LSG was performed . Results Mean volume of the entire stomach was 1,553 cc ( 600–2,000 cc ) and that of the sleeve 129 cc ( 90–220 cc ) , i.e. , 10 % ( 4–17 % ) and that of the removed stomach was 795 cc ( 400–1,500 cc ) . The mean basal intragastric pressure of the whole stomach after insufflations of the abdominal cavity with CO2 to 15 mmHg was 19 mmHg ( 11–26 mmHg ) ; after occlusion and filling with saline it was 34 mmHg ( 21–45 mmHg ) . In the sleeved stomach , mean basal pressure was similar 18 mmHg ( 6–28 mmHg ) ; when filled with saline , pressure rose to 43 mmHg ( 32–58 mmHg ) . The removed stomach had a mean pressure of 26 mmHg ( 12–47 mmHg ) . There were no postoperative complications and no mortality . Conclusions The notably higher pressure in the sleeve , reflecting its markedly lesser distensibility compared to that of the whole stomach and of the removed fundus , indicates that this may be an important element in the mechanism of weight loss BACKGROUND The effect of bariatric surgery on iron absorption is only partially known . OBJECTIVE The objective was to study the effects of sleeve gastrectomy ( SG ) and Roux-en-Y gastric bypass ( RYGBP ) on heme- and nonheme-iron absorption and iron status . DESIGN Fifty-eight menstruating women were enrolled in this prospect i ve study [ mean ( ±SD ) age : 35.9 ± 9.1 y ; weight : 101.7 ± 13.5 kg ; BMI ( in kg/m² ) : 39.9 ± 4.4 ] . Anthropometric , body-composition , dietary , and hematologic indexes and heme- and nonheme-iron absorption-using a st and ardized meal containing 3 mg Fe-were determined before and 12 mo after surgery . Forty-three subjects completed the 12-mo follow-up . Iron supplements were strictly controlled . RESULTS Heme-iron absorption was 23.9 % before and 6.2 % 12 mo after surgery ( P < 0.0001 ) . Nonheme-iron absorption decreased from 11.1 % to 4.7 % ( P < 0.0001 ) . No differences were observed by type of surgery . Iron intakes from all sources of supplements were 27.9 ± 6.2 mg/d in the SG group and 63.2 ± 21.1 mg/d in the RYGBP group ( P < 0.001 ) . Serum ferritin and total-body iron decreased more after RYGBP than after SG . CONCLUSIONS Iron ( heme and nonheme ) absorption is markedly reduced after SG and RYGBP . The magnitude of the decrease in heme-iron absorption is greater than that of nonheme iron . The amounts suggested as iron supplements may need to be increased to effectively prevent iron-status impairment Background Bariatric surgery is currently the most effective treatment for morbid obesity . It provides not only substantial weight loss , but also resolution of obesity-related comorbidities . Laparoscopic sleeve gastrectomy ( LSG ) has rapidly been gaining in popularity . However , there are limited data on the reduction of obesity-related comorbidities for LSG compared to laparoscopic Roux-en-Y gastric bypass ( LRYGB ) . The aim of this study was to assess the effectiveness of laparoscopic LSG versus LRYGB for the treatment of obesity-related comorbidities . Methods A total of 558 patients who underwent either LSG or LRYGB for morbid obesity at the Westchester Medical Center between April 2008 and September 2010 were included . Data were collected prospect ively into a computerized data base and review ed for this study . Fisher ’s exact test analyses compared 30-day , 6-month , and 1-year outcomes of obesity-related comorbidities . Results A total of 558 patients were included in the analysis of obesity-related comorbidity resolution ; 200 underwent LSG and 358 underwent LRYGB . After 1 year , 86.2 % of the LSG patients had one or more comorbidities in remission compared to 83.1 % LRYGB patients ( P = 0.688 ) . With the exception of GERD ( −0.09 vs. 50 % ; P < 0.001 ) , similar comorbidity remission rates were observed between LSG and LRYGB for sleep apnea ( 91.2 vs. 82.8 % ; P = 0.338 ) , hyperlipidemia ( 63 vs. 55.8 % ; P = 0.633 ) , hypertension ( 38.8 vs. 52.9 % ; P = 0.062 ) , diabetes ( 58.6 vs. 65.5 % ; P = 0.638 ) , and musculoskeletal disease ( 66.7 vs. 79.4 % ; P = 0.472 ) . Conclusions Laparoscopic sleeve gastrectomy markedly improves most obesity-related comorbidities . Compared to LRYGB , LSG may have equal in reducing sleep apnea , hyperlipidemia , hypertension , diabetes , and musculoskeletal disease . LRYGB appears to be more effective at GERD resolution than LSG Background The long-term efficacy of laparoscopic Roux-en-Y gastric bypass ( RYGB ) in the treatment of morbid obesity has been demonstrated . Laparoscopic sleeve gastrectomy ( SG ) as a single procedure has shown promising short-term results , but the long-term efficacy of SG has not yet been demonstrated . The aim of this study was to determine the preliminary 30-day morbidity and mortality of RYGB and SG in a prospect i ve multicenter r and omized setting . Methods A total of 240 morbidly obese ( BMI = 35–66 kg/m² ) patients evaluated by a multidisciplinary team were r and omized to undergo either RYGB or SG . There were 117 patients in the RYGB group and 121 in the SG group ; two patients had to be excluded after r and omization . Both study groups were comparable regarding age , gender , BMI , and comorbidities . Results There was no 30-day mortality . The median operating time was significantly shorter in the SG group ( 66 min vs. 94 min , p < 0.001 ) . All complications were recorded thoroughly . There were 7 ( 5.8 % ) major complications following SG and 11 ( 9.4 % ) after RYGB ( p = 0.292 ) . Nine ( 7.4 % ) SG patients and 20 ( 17.1 % ) RYGB patients had minor complications ( p = 0.023 ) . The overall morbidity was 13.2 % after SG and 26.5 % after RYGB ( p = 0.010 ) . There were three ( 2.5 % ) early reoperations after SG and four ( 3.3 % ) after RYGB ( p = 0.719 ) . Conclusions At 30-day analysis SG is associated with a shorter operating time and fewer early minor complications compared to RYGB . There were no significant differences in major complications or early reoperations . Long-term follow-up is required to determine the effect on weight loss , resolution of obesity-related comorbidities , and improvement of quality of life Background : Bariatric surgery is currently the most effective treatment in morbidly obese patients , leading to durable weight loss . Objective : In this prospect i ve double blind study , we aim to evaluate and compare the effects of laparoscopic Roux-en-Y gastric bypass ( LRYGBP ) with laparoscopic sleeve gastrectomy ( LSG ) on body weight , appetite , fasting , and postpr and ial ghrelin and peptide-YY ( PYY ) levels . Methods : After r and omization , 16 patients were assigned to LRYGBP and 16 patients to LSG . Patients were reevaluated on the 1st , 3rd , 6th , and 12th postoperative month . Blood sample s were collected after an overnight fast and in 6 patients in each group after a st and ard 420 kcal mixed meal . Results : Body weight and body mass index ( BMI ) decreased markedly ( P < 0.0001 ) and comparably after either procedure . Excess weight loss was greater after LSG at 6 months ( 55.5 % ± 7.6 % vs. 50.2 % ± 6.5 % , P = 0.04 ) and 12 months ( 69.7 % ± 14.6 % vs. 60.5 % ± 10.7 % , [ P = 0.05 ] ) . After LRYGBP fasting ghrelin levels did not change significantly compared with baseline ( P = 0.19 ) and did not decrease significantly after the test meal . On the other h and , LSG was followed by a marked reduction in fasting ghrelin levels ( P < 0.0001 ) and a significant suppression after the meal . Fasting PYY levels increased after either surgical procedure ( P ≤ 0.001 ) . Appetite decreased in both groups but to a greater extend after LSG . Conclusion : PYY levels increased similarly after either procedure . The markedly reduced ghrelin levels in addition to increased PYY levels after LSG , are associated with greater appetite suppression and excess weight loss compared with LRYGBP Introduction Roux-en-Y gastric bypass ( RYGB ) is considered the gold st and ard bariatric procedure with documented safety and effectiveness . Laparoscopic sleeve gastrectomy ( LSG ) is a newer procedure being done with increasing frequency . R and omized comparisons of LSG and other bariatric procedures are limited . We present the results of the first prospect i ve r and omized trial comparing LSG and RYGB in the Polish population . Aim To assess the efficacy and safety of LSG versus RYGB in the treatment of morbid obesity and obesity-related comorbidities . Material and methods Seventy-two morbidly obese patients were r and omized to RYGB ( 36 patients ) or LSG ( 36 patients ) . Both groups were comparable regarding age , gender , body mass index ( BMI ) and comorbidities . The follow-up period was at least 12 months . Baseline and 6 and 12 month outcomes were analyzed including assessment of percent excess weight lost ( % EWL ) , reduction in BMI , morbidity ( minor , major , early and late complications ) , mortality , reoperations , comorbidities and nutritional deficiencies . Results There was no 30-day mortality and no significant difference in major complication rate ( 0 % after RYGB and 8.3 % after LSG , p > 0.05 ) or minor complication rate ( 16.6 % after RYGB and 10.1 % after LSG , p > 0.05 ) . There were no early reoperations after RYGB and 2 after LSG ( 5.5 % ) ( p > 0.05 ) . Weight loss was significant after RYGB and LSG but there was no difference between both groups at 6 and 12 months of follow-up . At 12 months % EWL in RYGB and LSG groups reached 64.2 % and 67.6 % respectively ( p > 0.05 ) . There was no significant difference in the overall prevalence of comorbidities and nutritional deficiencies . Conclusions Both LSG and RYGB produce significant weight loss at 6 and 12 months after surgery . The procedures are equally effective with regard to % EWL , reduction in BMI and amelioration of comorbidities at 6 and 12 months of follow-up . Laparoscopic sleeve gastrectomy and RYGB are comparably safe techniques with no significant differences in minor and major complication rates at 6 and 12 months OBJECTIVES To determine the efficacies of 2 weight-reducing operations on diabetic control and the role of duodenum exclusion . DESIGN Double-blind r and omized controlled trial . SETTING Department of Surgery of the Min-Sheng General Hospital , National Taiwan University . PATIENTS We studied 60 moderately obese patients ( body mass index > 25 and < 35 ) aged > 30 to < 60 years who had poorly controlled type 2 diabetes mellitus ( T2DM ) ( hemoglobin A(1c ) [ HbA(1c ) ] > 7.5 % ) after conventional treatment ( > 6 months ) from September 1 , 2007 , through June 30 , 2008 . Patients and observers were masked during the follow-up , which ended in 2009 , 1 year after final enrollment . INTERVENTIONS Gastric bypass with duodenum exclusion ( n = 30 ) vs sleeve gastrectomy without duodenum exclusion ( n = 30 ) . MAIN OUTCOME MEASURES The primary outcome was remission of T2DM ( fasting glucose < 126 mg/dL and HbA(1c ) < 6.5 % without glycemic therapy ) . Secondary measures included weight and metabolic syndrome . Analysis was by intention to treat . RESULTS Of the 60 patients enrolled , all completed the 12-month follow-up . Remission of T2DM was achieved by 28 ( 93 % ) in the gastric bypass group and 14 ( 47 % ) in the sleeve gastrectomy group ( P = .02 ) . Participants assigned to gastric bypass had lost more weight , achieved a lower waist circumference , and had lower glucose , HbA(1c ) , and blood lipid levels than the sleeve gastrectomy group . No serious complications occurred in either group . CONCLUSIONS Participants r and omized to gastric bypass were more likely to achieve remission of T2DM . Duodenum exclusion plays a role in T2DM treatment and should be assessed . Trial Registration clinical trials.gov Identifier : NCT00540462 ( http://www . clinical trials.gov ) BACKGROUND A paucity of information is available on the comparative body composition changes after bariatric procedures . The present study reports on the body mass index ( BMI ) and body composition changes after 4 procedures by a single group . METHODS At the initial consultation , the weight and body composition of the patients undergoing 4 different bariatric procedures were measured by bioimpedance ( Tanita 310 ) . Follow-up examinations were performed at 1 year and at subsequent visits after surgery . Analysis of variance was used to compare the postprocedure BMI and body composition . Analysis of covariance was used to adjust for baseline differences . RESULTS A total of 101 gastric bypass ( GB ) patients were evaluated at 19.1 + or - 10.6 months , 49 biliopancreatic diversion with the duodenal switch ( BPD/DS ) patients at 27.5 + or - 16.3 months , 41 adjustable gastric b and ( AGB ) patients at 21.4 + or - 9.2 months , and 30 sleeve gastrectomy ( SG ) patients at 16.7 + or - 5.6 months ( P < .0001 ) . No differences were found in patient age or gender among the 4 groups . The mean preoperative BMI was significantly different among the 4 groups ( P < .0001 ) : 61.4 kg/m(2 ) , 53.2 , 46.7 , and 44.3 kg/m(2 ) for the SG , BPD/DS , GB , and AGB group , respectively . The postoperative BMI adjusted for baseline differences was 27.8 ( difference 23.6 + or - 8.3 ) , 32.5 ( difference 15.6 + or - 5.0 ) , 37.2 ( difference 18.2 + or - 8.2 ) , and 39.5 kg/m(2 ) ( difference 7.5 + or - 4.3 ) for the BPD/DS , GB , SG , and AGB groups , respectively ( P < .0001 ) . The percentage of excess weight loss was 84 % , 70 % , 49 % , and 38 % for the BPD/DS , GB , SG , and AGB groups , respectively ( P < .0001 ) . The postoperative percentage of body fat adjusted for baseline differences was 25.7 % ( 23.9 % + or - 7.0 % ) 32.7 % ( 16.1 % + or - 10.5 % ) 37.7 % ( 16.7 % + or - 5.6 % ) , and 42 % ( 6.0 % + or - 6.8 % ) for the BPD/DS , GB , SG , and AGB groups , respectively ( P < .0001 ) . The lean body mass changes were reciprocal . CONCLUSION Although the BPD/DS procedure reduced the BMI the most effectively and promoted fat loss , all the procedures produced weight loss . The AGB procedure result ed in less body fat loss within 21.5 months than SG within 16.7 months . Longer term observation is indicated Background Laparoscopic sleeve gastrectomy ( LSG ) has been gaining acceptance because it has shown good short- and mid-term results as a single procedure for morbid obesity . The aim of this study was to compare short- and mid-term results between laparoscopic Roux-en-Y gastric bypass ( LRYGB ) and LSG . Methods Observational retrospective study from a prospect i ve data base of patients undergoing LRYGB and LSG between 2004 and 2011 , where 249 patients ( mean age 44.7 years ) were included . Patients were followed at 1 , 3 , 6 , 12 , and 18 months , and annually thereafter . Short- and mid-term weight loss , comorbidity improvement or resolution , postoperative complications , re- interventions , and mortality were evaluated . Results One hundred thirty-five LRYGB and 114 LSG were included . Significant statistical differences between LRYGB and LSG were found in operative time ( 153 vs. 93 min . p < 0.001 ) , minor postoperative complications ( 21.5 % vs. 4.4 % , p = 0.005 ) , blood transfusions ( 8.8 % vs. 1.7 % , p = 0.015 ) , and length of hospital stay ( 4 vs. 3 days , p < 0.001 ) . There were no differences regarding major complications and re- interventions . There was no surgery-related mortality . The percentage of excess weight loss up to 4 years was similar in both groups ( 66 ± 13.7 vs. 65 ± 14.9 % ) . Both techniques showed similar results in comorbidities improvement or resolution at 1 year . Conclusions There is a similar short- and mid-term weight loss and 1-year comorbidity improvement or resolution between LRYGB and LSG , although minor complication rate is higher for LRYGB . Results of LSG as a single procedure need to be confirmed after a long-term follow-up Context : Hyperglycemia resolves quickly after bariatric surgery , but the underlying mechanism and the most effective type of surgery remains unclear . Objective : To examine glucose metabolism and β-cell function in patients with type 2 diabetes mellitus ( T2DM ) after two types of bariatric intervention ; Roux-en-Y gastric bypass ( RYGB ) and gastric restrictive ( GR ) surgery . Design : Prospect i ve , nonr and omized , repeated- measures , 4-week , longitudinal clinical trial . Patients : In all , 16 T2DM patients ( 9 males and 7 females , 52±14 years , 47±9 kg m−2 , HbA1c 7.2±1.1 % ) undergoing either RYGB ( N=9 ) or GR ( N=7 ) surgery . Outcome measures : Glucose , insulin secretion , insulin sensitivity at baseline , and 1 and 4 weeks post-surgery , using hyperglycemic clamps and C-peptide modeling kinetics ; glucose , insulin secretion and gut-peptide responses to mixed meal tolerance test ( MMTT ) at baseline and 4 weeks post-surgery . Results : At 1 week post-surgery , both groups experienced a similar weight loss and reduction in fasting glucose ( P<0.01 ) . However , insulin sensitivity increased only after RYGB , ( P<0.05 ) . At 4 weeks post-surgery , weight loss remained similar for both groups , but fasting glucose was normalized only after RYGB ( 95±3 mg 100 ml−1 ) . Insulin sensitivity improved after RYGB ( P<0.01 ) and did not change with GR , whereas the disposition index remained unchanged after RYGB and increased 30 % after GR ( P=0.10 ) . The MMTT elicited a robust increase in insulin secretion , glucagon-like peptide-1 ( GLP-1 ) levels and β-cell sensitivity to glucose only after RYGB ( P<0.05 ) . Conclusion : RYGB provides a more rapid improvement in glucose regulation compared with GR . This improvement is accompanied by enhanced insulin sensitivity and β-cell responsiveness to glucose , in part because of an incretin effect Background Sleeve gastrectomy ( SG ) and Roux-en-Y gastric bypass ( RYGBP ) are associated with similar type 2 diabetes mellitus ( T2DM ) resolution rates for morbidly obese subjects . However , the mechanisms underlying the resolution of T2DM after SG have not been clarified to date . This study aim ed to compare the early changes in gastrointestinal hormones involved in insulin and glucagon secretion in morbidly obese T2DM subjects undergoing SG or RYGBP . Methods This prospect i ve study investigated 12 subjects with T2DM who had undergone SG ( n = 6 ) or RYGBP ( n = 6 ) . Five body mass index ( BMI ) -matched obese non-diabetic subjects and five BMI -matched obese diabetic subjects served as control subjects . Glucose , insulin , glucagon , glucagon-like peptide 1 ( GLP-1 ) , glucose-dependent insulinotropic polypeptide ( GIP ) , and GLP-2 were determined after a st and ardized mixed liquid meal before surgery and 6 weeks afterward . Results After 6 weeks , five of the six subjects in each surgical group presented with T2DM remission , although the area under the curve (AUC)0–120 of glucose was greater than that of the non-diabetic control subjects ( P < 0.01 ) . Postsurgically , the indices of insulin and glucagon secretion were comparable between the two surgical groups . The AUC0–120 of GLP-1 ( P < 0.05 ) and GLP-2 ( P < 0.05 ) was significantly and comparably enlarged after SG and RYGB . The postsurgical GIP response was significantly associated with the glucagon response throughout the meal test ( ρ = 0.747 ; P < 0.01 ) . Conclusions The data show that in a cohort of morbidly obese T2DM subjects , SG and RYGBP are associated with an early improvement in glucose tolerance , similar changes in insulin and glucagon secretion , and a similar GLP-1 , GIP , and GLP-2 response to a st and ardized mixed liquid meal Background This study aims to report glycolipid changes after sleeve gastrectomy ( SG ) or Roux-en-Y gastric bypass ( RYGB ) in the setting of a prospect i ve r and omized clinical trial . Methods One hundred patients were r and omly assigned to RYGB ( n = 45 ) and SG ( n = 55 ) . Fasting glucose , insulin , glycated hemoglobin ( HbA1c% ) , triglycerides , and serum cholesterol ( total , HDL , and LDL ) were evaluated at inclusion and after 1 , 3 , 6 , and 12 months . The index for homeostasis model assessment of insulin resistance ( HOMA-IR ) and β cell function ( HOMA-B ) were assessed . Results Mean postoperative 1- , 3- , 6- , and 12-month excess weight loss was 25.39 , 43.47 , 63.75 , and 80.38 % after RYGB and 25.25 , 51.32 , 64.67 , and 82.97 % after SG , respectively . Mean fasting glucose and fasting serum insulin were similarly and statistically significantly reduced in both RYGB and SG . Mean HOMA-IR improved in both groups , particularly in case of high preoperative values , and mean HOMA-B improved at 1 year after RYGB . HbA1c% dropped from 5.66 % ( SD = 0.61 ) to 5.57 % ( SD = 0.32 ) after RYGB and from 5.64 % ( SD = 0.43 ) to 5.44 % ( SD = 0.43 ) after SG . Total cholesterol was significantly higher at 1 month ( p = 0.04 ) , 3 months ( p = 0.03 ) , and 1 year ( p = 0.005 ) after SG as compared to RYGB . LDL cholesterol decreased significantly after RYGB at 1 month ( p = 0.03 ) , 3 months ( p = 0.0001 ) , and 1 year ( p = 0.0004 ) as compared to SG . HDL cholesterol was increased at 1 year in the RYGB group but not in the SG group . Triglycerides decreased similarly in both groups . Conclusions Short-term glycemic control was comparable after SG and RYGB . An improved lipid profile was noted after RYGB in patients with abnormal preoperative values Laparoscopic Roux-en-Y gastric bypass ( LRYGB ) is one of the most widely used bariatric procedures today , and laparoscopic sleeve gastrectomy ( LSG ) as a single-stage procedure for the treatment of morbid obesity is becoming increasingly popular . In this study , we prospect ively compared both techniques in order to establish whether there is any superiority of one over the other based on morbidity and effectiveness . From January 2008 to December 2008 , 117 obese patients with indication for bariatric surgery were assigned by patient choice after informed consent to either a LRYGB procedure ( n = 75 ) or a LSG procedure ( n = 42 ) . We determined operative time , length of stay , morbidity , co-morbidity outcomes , and excess weight loss at 1 year postoperative . Both groups were comparable in age , sex , body mass index , and co-morbidities . Mean operative time of LSG was 82 min while LRYGB was 98 min ( p < 0.05 ) . Differences in length of stay , major complications , improvement in co-morbidities , and excess weight loss were not significant ( p > 0.05 ) . One year after surgery , average excess weight loss was 86 % in LRYGB and 78.8 % in LSG ( p > 0.05 ) . In the short term , both techniques are comparable regarding safety and effectiveness , so not one procedure is clearly superior to the other Type 2 diabetes ( T2D ) remission after bariatric procedures has been highlighted in many retrospective and some recent prospect i ve studies . However , in the most recent prospect i ve study , more than 50 % of patients did not reach T2D remission at 1 year . Our aim was to identify baseline positive predictors for T2D remission at 1 year after bariatric surgery and to build a preoperative predictive score . We analysed the data concerning 161 obese operated on between June 2007 and December 2010 . Among them , 46 were diabetic and were included in the study —11 laparoscopic adjustable gastric b and ing ( LAGB ) , 26 Roux-en-Y gastric bypass ( RYGB ) and 9 sleeve gastrectomy ( SG ) . We compared anthropometric and metabolic features during 1 year of follow-up . A receiver operating characteristic analysis was performed to predict T2D remission . RYGB and SG were similarly efficient for body weight loss and more efficient than LAGB ; 62.8 % of patients presented with T2DM remission at 1 year , with no significant difference according to the surgical procedure . A 1-year body mass index ( BMI ) < 35 kg m−2 was predictive of T2DM remission whatever the procedure . The preoperative predictive factors of diabetes remission were baseline BMI ≤50 kg m−2 , duration of type 2 diabetes ≤4 years , glycated haemoglobin ≤7.1 % , fasting glucose < 1.14 g/l and absence of insulin therapy . A short duration of diabetes and good preoperative glycaemic control increase the rate of T2DM remission 1 year after surgery . Preoperative metabolic data could be of greater importance than the choice of bariatric procedure The laparoscopic Roux Y gastric bypass ( LRYGB ) and the laparoscopic gastric sleeve resection are frequently used methods for the treatment of morbid obesity . Quality of life , weight loss and improvement of the co-morbidities were examined . Match pair analysis of the prospect ively collected data base of the 47 gastric bypass and 47 gastric sleeve resection patients operated on in our hospital was performed . The quality of life parameters were measured with two st and ard question naires ( SF 36 and Moorehead – Ardelt II ) . The mean preoperative and postoperative BMI was in gastric bypass group 46.1 and 28.1 kg/m2 ( mean follow-up : 15.7 months ) and in gastric sleeve group 50.3 and 33.5 kg/m2 ( mean follow-up : 38.3 months ) . The SF 36 question naire yielded a mean total score of 671 for the bypass and 611 for the sleeve resection patients ( p = 0.06 ) . The Moorehead – Ardelt II test signed a total score of 2.09 for gastric bypass versus 1.70 for gastric sleeve patients ( p = 0.13 ) . Ninety percent of the diabetes was resolved in the bypass and 55 % in the sleeve resection group . Seventy-three percent of the hypertension patients needed no more antihypertensive treatment after gastric bypass and 30 % after sleeve resection . Ninety-two percent of the gastro-oesophageal reflux were resolved in the bypass group and 25 % in the sleeve ( with 33 % progression ) group . Ninety-four percent of the patients were satisfied with the result after gastric bypass and 90 % after sleeve resection . The patients have scored a high level of satisfaction in both study groups . The gastric bypass is associated with a trend toward a better quality of life without reaching statistical significance , pronounced loss of weight and more remarkable positive effects on the co-morbidities comparing with the gastric sleeve resection Gastric bypass ( GBP ) has proved its efficacy 30 years ago in the management of diabetes mellitus ( T2DM ) for severe obese patients . More recently , interesting results have been published after sleeve gastrectomy ( SG ) in the same indication . Between 2005 and 2008 , three bariatric centers have prospect ively collected the data of T2DM patients treated by laparoscopic gastric bypass ( LGBP ) or laparoscopic sleeve gastrectomy ( LSG ) . Effects on hemoglobin A1c ( HbA1c ) , pharmacological treatment and excess weight loss after 1 year of surgery have been analyzed . All patients ( 35 LGBP and 33 LSG ) were treated with oral anti-diabetics ( OAD ) or insulin before surgery ( 32 OAD and three insulin in LGBP group and 27 OAD and six insulin in LSG group ) . The average body mass index ( BMI ) in the LGBP group was 47.9 and 50.6 kg/m² in the LSG group . At 1 year after surgery , the average HbA1c lost was 2,537 in the GBP group and 2,175 in the SG group . T2DM had resolved ( withdrawal of pharmacological treatment ) in 60 % of the LGBP group and 75.8 % of the LSG group . Reduced use of pharmacological therapy was noted in 31.42 % of the LGBP group and 15.15 % of the LSG group . Percentage excess weight loss and BMI lost were 56.35 % and 29.75 % in the LGBP group and 60.11 % and 29.80 % in the LSG group , respectively . During short-term follow-up , the impact on regulation of HbA1c blood level of LGBP or LSG is important . At 1 year after surgery , LSG seems to be as effective as LGBP for the management of T2DM in severely obese patients BACKGROUND Very few studies have compared laparoscopic Roux-en-Y gastric bypass ( LRYGB ) and laparoscopic sleeve gastrectomy ( LSG ) outcomes or analyzed improvement in cardiovascular risk ( CVR ) after bariatric surgery . None of the studies considered the Mediterranean population . Our primary objective was to compare the 10-year estimated CVR reduction achieved by LRYGB and LSG in Spanish subjects with severe obesity . The secondary objectives were to compare the techniques in terms of weight loss and co-morbidity improvement . The study was performed at a university hospital in Barcelona , Spain . METHODS A 12-month prospect i ve cohort study of 140 consecutive patients ( 95 LRYGB and 45 LSG ) compared the 2 surgical intervention groups to study the percentage of excess weight loss , resolution and improvement/resolution of co-morbidities , and effect on CVR using both the Framingham risk score ( FRS ) and the Registre Gironí del Cor ( REGICOR ) model . RESULTS At 12 months , the overall CVR decreased from 6.6 % to 3.4 % using the FRS and from 3.7 % to 1.9 % using the REGICOR score . Neither model found a difference between the 2 surgical intervention groups in decreased postoperative CVR risk , with a FRS of 3.4 % ± 2.2 % for LRYGB versus 3.3 % ± 2.1 % for LSG ( P = .872 ) and a REGICOR score of 1.9 % ± 1.5 % versus 1.8 % ± 1.6 % , respectively ( P = .813 ) . No differences were observed in the percentage of excess weight loss or the resolution of type 2 diabetes mellitus and hypertension . The hypercholesterolemia improvement/resolution rate was lower in the LSG group than in the LRYGB group . CONCLUSION Bariatric surgery reduces the estimated CVR by one half at 1 year after surgery . Except for the less-improved cholesterol metabolism , LSG , a restrictive technique , proved to be equally as effective at 1 year of follow-up as LRYGB Background Deficiencies in micronutrients after bariatric operations are frequent , despite routine supplementation . Main outcome measures were pre- and postoperative frequency of nutrient deficiencies and success rate of their treatment . Methods Between 5/2004 and 12/2006 , 136 patients ( m : f = 0:4 ) with an average body mass index of 45 ( 35–58 ) kg/m2 and age of 53 ( 21–66 ) years were prospect ively analysed . Laparoscopic Roux-Y-gastric bypass ( LRYGB ) was performed in 86 patients and laparoscopic sleeve gastrectomy ( LSG ) was performed in 50 patients . The patients were examined before surgery as well as 3 , 6 , 12 , 24 , 30 , and 36 months postoperatively using a st and ard protocol including laboratory tests . The mean follow-up time was 24.4 ( 12–40 ) months ; the follow-up rate was 100 % . Results Prior to surgery , 57 % of the patients had at least one deficiency , 23 % of whom had vitamin D3 deficiency . Frequent postoperative deficiencies after LSG were zinc , vitamin D3 , folic acid , iron , and vitamin B12 ; after LRYGB , vitamin B12 , vitamin D3 , zinc , and secondary hyperparathyroidism . No vitamin B1 or B6 deficiencies were found . Calcium levels were normal in all patients . Treatment of the deficiencies was mostly successful . Conclusion Preoperatively , 57 % of morbidly obese patients already had a deficiency . Postoperatively , significantly more vitamin B12 and vitamin D deficiencies and hyperparathyroidism were found in patients who had undergone LRYGB . After LSG , folate deficiency was more frequent ( but not significantly so ) . Calcium levels were normal in all patients ; therefore , parathyroid hormone and vitamin D3 levels are more sensitive markers for early detection of disorders of calcium metabolism . Iron deficiency anaemia is most efficiently treated by IV therapy Background Laparoscopic Roux-en-Y gastric bypass ( LRYGB ) is the most common bariatric technique . Laparoscopic sleeve gastrectomy ( LSG ) is a restrictive procedure ; the metabolic and endocrine effects of which remain unknown . We compared the effects of both procedures on glucose metabolism and fasting and meal-stimulated gut hormone levels . Methods Seven patients were r and omised to LRYGB and eight to LSG . All patients were evaluated before and at 3 and 12 months postoperatively . Plasma levels of glucose , insulin , ghrelin , leptin , peptide YY ( PYY ) , GLP-1 and pancreatic polypeptide were measured before and after 10 and 60 min of a st and ard test meal ingestion . Results Age , body mass index and preoperative hormone levels were similar in both groups . A significant reduction of plasma glucose and insulin levels was observed after surgery . Moreover , a normalisation of homeostatic model assessment for insulin resistance value was also seen after both procedures . The fasting and postpr and ial leptin levels were significantly lower in the LRYGB group . LSG was followed by a significant reduction in fasting ghrelin levels . In the LRYGB group , GLP-1 levels increased significantly after the test meal . Conclusions LRYGB and LSG markedly improved glucose homeostasis . Only LSG decreased fasting and postpr and ial ghrelin levels , whereas GLP-1 and PYY levels increased similarly after both procedures Background Few studies have evaluated the impact of hybrid versus purely restrictive bariatric surgery on lipid profile , with the results being contradictory . The effect of laparoscopic sleeve gastrectomy ( LSG ) and laparoscopic Roux-en-Y gastric bypass ( LRYGB ) on lipid profile was compared . Methods A nonr and omized prospect i ve cohort study was conducted on severely obese patients undergoing bariatric surgery . Indication for the type of surgical procedure was based on clinical criteria . Patients on lipid-lowering drugs and those that could not be matched for age , sex , and body mass index were excluded . Finally , 51 patients who underwent LSG and 51 undergoing LRYGB completed this study . Results During the first year post-surgery , no differences in percentage of excess weight loss and triglyceride reduction were found between groups . After LRYGR , low-density lipoprotein ( LDL ) cholesterol concentrations fell significantly ( 125.9 ± 29.3 to 100.3 ± 26.4 mg/dl , p < 0.001 ) , whereas no significant changes were observed in the LSG group ( 118.6 ± 30.7 to 114.6 ± 33.5 mg/dl , p = 0.220 ) . High-density lipoprotein ( HDL ) cholesterol increase was significantly greater after LSG ( 15.4 ± 13.1 mg/dl ) compared with LRYGB ( 9.4 ± 14.0 mg/dl , p = 0.032 ) . Factors independently associated with LDL cholesterol reduction were higher baseline total cholesterol and undergoing LRYGB . A greater increase in HDL cholesterol was associated with LSG , older age , and baseline HDL cholesterol . Conclusions LRYGB produces an overall improvement in lipid profile , with a clear benefit in all lipid fractions . Although LSG does not alter LDL cholesterol levels , its effect on HDL cholesterol is comparable to or greater than that obtained with malabsorptive techniques Background To investigate and compare food tolerance and gastrointestinal quality of life following three bariatric procedures approximately 2 to 4 years post-surgery : adjustable gastric b and ing ( AGB ) , Roux-en-Y gastric bypass ( RYGBP ) , and sleeve gastrectomy ( SG ) . A secondary aim was to test for a relationship between food tolerance and gastrointestinal quality of life . Methods In this prospect i ve cross-sectional study , participants ( including pre-surgery controls ) completed two question naires : a food tolerance question naire ( n = 129 ) and a Gastrointestinal Quality of Life Index ( GIQLI ) ( n = 119 ) . Kruskal – Wallis and Mann – Whitney tests were performed , and significance was adjusted using a post-hoc Bonferroni correction . Spearman 's rank correlation coefficients were calculated to evaluate the relationship between food tolerance and GIQLI scores . Results Food tolerance : the control and SG groups produced the highest median scores ( 24.5 and 24.0 , respectively ) , indicating superior food tolerance . The median score of the AGB group was significantly lower than all other groups ( 15.5 , P < 0.001 ) . Gastrointestinal quality of life : the SG group ranked superior , producing the highest median score ( 120.5 ) , which was significantly greater than the AGB ( 94.0 , P = 0.005 ) and control groups ( 96.0 , P = 0.006 ) . GIQLI scores correlated significantly with food tolerance scores ( r = 0.522 , P < 0.01 ) . The median excess weight loss was similar in the SG and RYGBP groups ( 76.3 % and 76.5 % ) , with the AGB group significantly lower at 38.2 % . Conclusions Food tolerance and gastrointestinal quality of life , 2 to 4 years post-surgery are ostensibly best after SG , followed closely by RYGBP . AGB appears the least effective across these parameters . A significant positive relationship between food tolerance and gastrointestinal quality of life was confirmed BACKGROUND To improve decision making in the treatment of extreme obesity , the risks of bariatric surgical procedures require further characterization . METHODS We performed a prospect i ve , multicenter , observational study of 30-day outcomes in consecutive patients undergoing bariatric surgical procedures at 10 clinical sites in the United States from 2005 through 2007 . A composite end point of 30-day major adverse outcomes ( including death ; venous thromboembolism ; percutaneous , endoscopic , or operative reintervention ; and failure to be discharged from the hospital ) was evaluated among patients undergoing first-time bariatric surgery . RESULTS There were 4776 patients who had a first-time bariatric procedure ( mean age , 44.5 years ; 21.1 % men ; 10.9 % nonwhite ; median body-mass index [ the weight in kilograms divided by the square of the height in meters ] , 46.5 ) . More than half had at least two coexisting conditions . A Roux-en-Y gastric bypass was performed in 3412 patients ( with 87.2 % of the procedures performed laparoscopically ) , and laparoscopic adjustable gastric b and ing was performed in 1198 patients ; 166 patients underwent other procedures and were not included in the analysis . The 30-day rate of death among patients who underwent a Roux-en-Y gastric bypass or laparoscopic adjustable gastric b and ing was 0.3 % ; a total of 4.3 % of patients had at least one major adverse outcome . A history of deep-vein thrombosis or pulmonary embolus , a diagnosis of obstructive sleep apnea , and impaired functional status were each independently associated with an increased risk of the composite end point . Extreme values of body-mass index were significantly associated with an increased risk of the composite end point , whereas age , sex , race , ethnic group , and other coexisting conditions were not . CONCLUSIONS The overall risk of death and other adverse outcomes after bariatric surgery was low and varied considerably according to patient characteristics . In helping patients make appropriate choices , short-term safety should be considered in conjunction with both the long-term effects of bariatric surgery and the risks associated with being extremely obese . ( Clinical Trials.gov number , NCT00433810 . BACKGROUND Laparoscopic sleeve gastrectomy ( LSG ) is gaining acceptance in the bariatric community as a definitive weight loss procedure ; however , longitudinal data remain limited . The objective of this study was to compare weight loss results of LSG with laparoscopic Roux-en-Y gastric bypass ( LRYGB ) up to 5 years postoperatively using anthropometric measurements . METHODS Prospect ively collected bariatric data base at the Naval Medical Center San Diego was retrospectively review ed from 2005 - 2011 . Anthropometric factors , including weight and hip circumference were measured during st and ard yearly follow-up appointments . Surgical outcomes were tested by the Student t test and demographic variables by Fisher 's exact and Wilcoxon rank-sum tests . RESULTS Follow-up was achieved in 147/226 LRYGB versus 130/208 LSG at year 1 , 92/195 versus 81/151 at year 2 , 64/145 versus 50/100 at year 3 , 32/81 versus 18/54 at year 4 , and 12/42 versus 14/15 at year 5 . The excess weight loss ( EWL ) for LRYGB versus LSG was 72 % versus 64.7 % at 1 year ( P = .002 ) , 71.3 % versus 65.5 % at 2 years ( P = .113 ) , and 68.3 % versus 57.4 % at 5 years ( P = .252 ) , respectively . Similarly , the body mass index ( BMI ) decrease was statistically significant at 1 year ( P = .001 ) but not on subsequent annual visits . Mean percent body adiposity index ( BAI ) decrease was 28.4 % for LRYGB versus 26.8 % for LSG at 1 year ( P = .679 ) and 21.8 % versus 29.8 % at 2 years ( P = .134 ) , respectively . Weight loss measured in terms of % EWL and decrease in BMI and BAI did not show significance between LRYGB and LSG 2 years after surgery . CONCLUSION Our study provides similar long-term weight loss between LSG and LRYGB , and therefore , LSG is a viable option as a definitive bariatric procedure |
1,626 | 17,938,702 | CONCLUSIONS Gliadel is an option for selected patients with newly diagnosed malignant glioma where a near gross total resection is possible .
Gliadel is also an option for patients with surgically resectable recurrent malignant glioma | QUESTION What is the safety and efficacy of interstitial chemotherapy with carmustine-loaded polymers ( Gliadel wafers : MGI Pharma , Bloomington , MN , U.S.A. ) in the treatment of newly diagnosed or recurrent malignant glioma ( that is , glioblastoma multiforme , anaplastic astrocytoma , anaplastic oligoastrocytoma , and anaplastic oligodendroglioma ) ?
PERSPECTIVES Malignant glioma is the most common type of primary brain tumour in adults .
In general , efficacy of systemic therapy in this patient population has been disappointing , and novel treatment approaches are needed . | A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea ( BCNU ) wafers ( Gliadel wafers ) prolong survival in patients with recurrent glioblastoma multiforme . A previously completed phase 3 trial , also placebo controlled , in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers . Because of the small number of patients in that trial , a larger phase 3 trial was performed to confirm these results . Two hundred forty patients were r and omized to receive either BCNU or placebo wafers at the time of primary surgical resection ; both groups were treated with external beam radiation postoperatively . The two groups were similar for age , sex , Karnofsky performance status ( KPS ) , and tumor histology . Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group ( log-rank P -value stratified by country = 0.03 ) , with a 29 % reduction in the risk of death in the treatment group . When adjusted for factors affecting survival , the treatment effect remained positive with a risk reduction of 28 % ( P = 0.03 ) . Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group ( P < /= 0.05 ) . Adverse events were comparable for the 2 groups , except for CSF leak ( 5 % in the BCNU wafer-treated group vs. 0.8 % in the placebo-treated group ) and intracranial hypertension ( 9.1 % in the BCNU wafer-treated group vs. 1.7 % in the placebo group ) . This study confirms that local chemotherapy with BCNU wafers is well tolerated and offers a survival benefit to patients with newly diagnosed malignant glioma The results of a multi-institutional phase I trial evaluating the safety of surgically implanted biodegradable 1,3-bis(chloro-ethyl)-1-nitrosourea ( BCNU ) impregnated polymer as theinitial therapy for malignant brain tumors are reported . This is the first study of locally delivered BCNU and st and ard external beam radiation therapy ( XRT ) given concurrently . Twenty-two patients were treated at three hospitals . The entry criteria were : single unilateral tumor focus larger than 1 cm3 ; age over 18 years ; Karnofsky Performance Score ( KPS ) of at least 60 h ; and an intra-operative diagnosis of malignant glioma . Twenty-one of twenty-two patients had glioblastoma multiforme . After surgery , seven or eight BCNU-loaded polyanhydride polymer discs ( 7.7 mg BCNU each ) were placed in the resection cavity . Postoperatively , all patients received st and ard radiation therapy ; none received additional chemotherapy in the first 6 months . Neurotoxicity , systemic toxicity , and survival were assessed . No perioperative mortality was seen . Neurotoxicity was equivalent to that occurring in other series of patients undergoing craniotomy and XRT without local chemotherapy . Systematic ally , no significant bone marrow suppression occurred , and there were no wound infections . Median survival in this group of older patients ( mean age=60 ) was 42 weeks , 8 patients survived 1 year , and 4 patients survived more than 18 months . Interstitial chemotherapy with BCNU-polymer with subsequent radiation therapy appears to be safe as an initial therapy . Several long-term survivors in this group of older patients with predominantly glioblastoma suggests efficacy in some patients . Dose escalation and efficacy trials are planned to further evaluate interstitial chemotherapy for the initial treatment of malignant gliomas OBJECTIVE To find out the effect of carmustine ( bischloroethyl-nitrosourea ) combined with a biodegradable polymer in the treatment of malignant ( Grade s III and IV ) gliomas , applied locally , at the time of the primary operation . METHODS Prospect i ve , r and omized double-blind study of an active treatment group versus a placebo group . Conducted at the Departments of Neurosurgery of the University Hospitals of Helsinki , Tampere , and Turku in Finl and and Trondheim in Norway . The study consisted of 32 patients ( 16 in each treatment group ) enrolled between March 23 , 1992 , and March 19 , 1993 . The study was planned to include 100 patients but had to be terminated prematurely , because the drug that was being used had become unobtainable . The main outcome measures included the survival times of patients after the operations and the application of an active drug or placebo . RESULTS The median time from surgery to death was 58.1 weeks for the active treatment group versus 39.9 weeks for the placebo group ( P = 0.012 ) . For 27 patients with Grade IV tumors , the corresponding times were 39.9 weeks for the placebo group and 53.3 weeks for the active treatment group ( P = 0.008 ) . At the end of the study , six patients were still alive , five of whom belonged to the active treatment group . CONCLUSION Carmustine applied locally in a biodegradable polymer at the time of primary operation , seems to have a favorable effect on the life span of patients with high- grade gliomas PURPOSE This New Approaches to Brain Tumor Therapy CNS Consortium study sought to determine the maximum-tolerated dose ( MTD ) of carmustine ( BCNU ) that can be implanted in biodegradable polymers following resection of recurrent high- grade gliomas and the systemic BCNU exposure with increasing doses of interstitial BCNU . PATIENTS AND METHODS Forty-four adults underwent tumor debulking and polymer placement . Six patients per dose level were studied using polymers with 6.5 % , 10 % , 14.5 % , 20 % , and 28 % BCNU by weight . Toxicities were assessed 1 month after implantation by a safety monitoring committee to determine whether subsequent escalations should occur . Nine additional patients were studied at the MTD to confirm safety . BCNU blood levels were obtained before and after polymer implantation . RESULTS No dose-limiting toxicities were identified at the 6.5 % , 10 % , or 14.5 % dose levels , although difficulties with wound healing , seizures , and brain edema were noted . At the 20 % dose , these effects seemed more prominent , and six additional patients were treated at this dose and tolerated treatment well . Three of four patients receiving the 28 % polymers developed severe brain edema and seizures , and accrual to this cohort was stopped . Nine additional patients received 20 % polymer , confirming this as the MTD . Maximum BCNU plasma concentrations with the 20 % loaded polymers were 27 ng/mL. Overall median survival was 251 days . CONCLUSION The MTD of BCNU delivered in polymer to the surgical cavity is 20 % . This polymer provides five times more BCNU than st and ard commercially available BCNU polymers and results in minimal systemic BCNU exposure . Additional studies are needed to establish the efficacy of high-dose BCNU polymers OBJECTIVE To determine the risks and survival benefit associated with implantation of an absorbable , 1,3-bis(2chloroethyl)-1-nitrosourea-impregnated polymer wafer , we prospect ively studied patients with recurrent glioblastoma multiforme and compared them with a demographically matched cohort group . METHODS Over a 29-month period , 62 patients underwent operations . All had tumor growth despite st and ard treatment , a Karnofsky performance score of > or = 70 , and histopathological confirmation of glioblastoma . Seventeen patients underwent gross total resection with placement of 1,3-bis(2-chloroethyl)-1-nitrosourea wafers ( wafer group ) at a median 44 weeks from diagnosis ( 6 women , 11 men ; median age , 56 years ) . A cohort group of 45 patients undergoing surgery for recurrent glioblastoma during the same time period , but not receiving wafers , was identified . Surgery was performed at a median 47 weeks from diagnosis ( 14 women , 31 men ; median age , 54 years ) . RESULTS Within 6 weeks of surgery , 13 complications were identified in 8 patients in the wafer group . In the cohort group , 6 patients sustained 8 complications . We were unable to identify any survival advantage using Kaplan-Meier analysis . In the wafer group , median survival was 58 weeks from diagnosis and 14 weeks from wafer implantation . In the cohort group , median survival was 97 weeks from diagnosis and 50 weeks from operation . CONCLUSION 1,3-bis(2-chloroethyl)-1-Nitrosourea wafer implantation for recurrent glioblastoma was associated with a higher risk of postoperative complications , particularly those related to infection and wound healing . No clear survival benefit associated with wafer implantation was identified Malignant gliomas have been difficult to treat with chemotherapy . The most effective agent , BCNU ( carmustine ) , has considerable systemic toxicity and a short half-life in serum . To obviate these problems , a method has been developed for the local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers . Implantation of the drug-impregnated polymer at the tumor site allows prolonged local exposure with minimal systemic exposure . In this Phase I-II study , 21 patients with recurrent malignant glioma were treated with BCNU released interstitially by means of a polyanhydride biodegradable polymer implant . Up to eight polymer wafers were placed in the resection cavity intraoperatively , upon completion of tumor debulking . The polymer releases the therapeutic drug for approximately 3 weeks . Three increasing concentrations of BCNU were studied ; the treatment was well tolerated at all three levels . There were no adverse reactions to the BCNU wafer treatment itself . The average survival period after reoperation was 65 weeks for the first dose group , 64 weeks for the second dose group , and 32 weeks for the highest dose group . The overall mean survival time was 48 weeks from reoperation and 94 weeks from the original operation . The overall median survival times were 46 weeks postimplant and 87 weeks from initial surgery . Eighteen ( 86 % ) of 21 patients lived more than 1 year from the time of their initial diagnosis and eight ( 38 % ) of 21 patients lived more than 1 year after intracranial implantation of the polymer . Frequent hematology , blood chemistry , and urinalysis tests did not reveal any systemic effect from this interstitial chemotherapy . Since the therapy is well tolerated and safe , a placebo-controlled clinical trial has been started . The trial will measure the effect of the second treatment dose on survival of patients with recurrent malignant glioma |
1,627 | 24,745,774 | Whilst population s with vascular disease appear to derive a range of psychological benefits from MBSR/MBCT intervention , the effects on physical parameters of disease are not yet established . | OBJECTIVE To determine the effectiveness of mindfulness-based stress reduction ( MBSR ) and mindfulness-based cognitive therapy ( MBCT ) on psychological and physical outcomes for people with vascular disease . | OBJECTIVE The aim was to examine the effects of a Mindfulness-Based Stress Reduction ( MBSR ) intervention on cardiovascular and cortisol activity during acute stress . METHOD Eighty-eight healthy community-dwelling individuals reporting elevated stress levels were r and omly assigned to the MBSR protocol or a waitlist control group . Before and after the intervention period they participated in a laboratory stress protocol consisting of mental arithmetic and speech tasks . Laboratory measurements included continuous cardiovascular parameters ( heart period , heart rate variability , and systolic and diastolic blood pressure [ SBP and DBP ] ) , and salivary cortisol . RESULTS Compared to the control group and controlling for age , sex , body mass index , and beta-blockers , the MBSR group showed larger pre- to postintervention decreases in overall SBP ( F(1 , 58 ) = 4.99 , p = .029 , partial η² = .08 ) and DBP ( F(1 , 58 ) = 11.09 , p = .002 , partial η² = .16 ) . In addition , the MBSR group exhibited smaller SBP and DBP stress-related changes from pre- to postintervention ( F(2 , 116 ) = 4.89 , p = .012 , partial η² = .08 ; F(2 , 116 ) = 6.07 , p = .007 , partial η² = .10 , respectively ) . No effects were obtained on other physiological measures . CONCLUSION MBSR may help reducing blood pressure levels and blood pressure reactivity to stress OBJECTIVE Emotional distress is common in out patients with diabetes , affecting ∼20–40 % of the patients . The aim of this study was to determine the effectiveness of group therapy with Mindfulness-Based Cognitive Therapy ( MBCT ) , relative to usual care , for patients with diabetes with regard to reducing emotional distress and improving health-related quality of life and glycemic control . RESEARCH DESIGN AND METHODS In the present r and omized controlled trial , 139 out patients with diabetes ( type 1 or type 2 ) and low levels of emotional well-being were r and omized to MBCT ( n = 70 ) or a waiting list group ( n = 69 ) . Primary outcomes were perceived stress ( Perceived Stress Scale ) , anxiety and depressive symptoms ( Hospital Anxiety and Depression Scale ) , mood ( Profiles of Mood States ) , and diabetes-specific distress ( Problem Areas In Diabetes ) . Secondary outcomes were health-related quality of life ( 12-Item Short-Form Health Survey ) , and glycemic control ( HbA1c ) . Assessment s were conducted at baseline and at 4 and 8 weeks of follow-up . RESULTS Compared with control , MBCT was more effective in reducing stress ( P < 0.001 , Cohen d = 0.70 ) , depressive symptoms ( P = 0.006 , d = 0.59 ) , and anxiety ( P = 0.019 , d = 0.44 ) . In addition , MBCT was more effective in improving quality of life ( mental : P = 0.003 , d = 0.55 ; physical : P = 0.032 , d = 0.40 ) . We found no significant effect on HbA1c or diabetes-specific distress , although patients with elevated diabetes distress in the MBCT group tended to show a decrease in diabetes distress ( P = 0.07 , d = 0.70 ) compared with the control group . CONCLUSIONS Compared with usual care , MBCT result ed in a reduction of emotional distress and an increase in health-related quality of life in diabetic patients who had lower levels of emotional well-being Objective Mindfulness-based stress reduction ( MBSR ) is an increasingly popular practice demonstrated to alleviate stress and treat certain health conditions . MBSR may reduce elevated blood pressure ( BP ) . Treatment guidelines recommend life-style modifications for BP in the prehypertensive range ( systolic BP [ SBP ] 120–139 mm Hg or diastolic BP [ DBP ] 80–89 mm Hg ) , followed by antihypertensives if BP reaches hypertensive levels . MBSR has not been thoroughly evaluated as a treatment of prehypertension . A r and omized clinical trial of MBSR for high BP was conducted to determine whether BP reductions associated with MBSR exceed those observed for an active control condition consisting of progressive muscle relaxation ( PMR ) training . Methods Fifty-six men ( 43 % ) and women ( 57 % ) averaging ( st and ard deviation ) 50.3 ( 6.5 ) years of age ( 91 % white ) with unmedicated BP in the prehypertensive range were r and omized to 8 weeks of MBSR or PMR delivered in a group format . Treatment sessions were administered by one treatment provider and lasted approximately 2.5 hours each week . Clinic BP was the primary outcome measure . Ambulatory BP was a secondary outcome measure . Results Analyses were based on intent to treat . Patients r and omized to MBSR exhibited a 4.8-mm Hg reduction in clinic SBP , which was larger than the 0.7-mm Hg reduction observed for PMR ( p = .016 ) . Those r and omized to MBSR exhibited a 1.9-mm Hg reduction in DBP compared with a 1.2-mm Hg increase for PMR ( p = .008 ) . MBSR did not result in larger decreases in ambulatory BP than in PMR . Conclusions MBSR result ed in a reduction in clinic SBP and DBP compared with PMR . Trial Registration Clinical Trials.gov identifier : NCT00440596 Hypertension affects a large proportion of urban African-American older adults . While there have been great strides in drug development , many older adults do not have access to such medicines or do not take them . Mindfulness-based stress reduction ( MBSR ) has been shown to decrease blood pressure in some population s. This has not been tested in low-income , urban African-American older adults . Therefore , the primary purpose of this pilot study was to test the feasibility and acceptability of a mindfulness-based program for low income , minority older adults provided in residence . The secondary purpose was to learn if the mindfulness-based program produced differences in blood pressure between the intervention and control groups . Participants were at least 62 years old and residents of a low-income senior residence . All participants were African-American , and one was male . Twenty participants were r and omized to the mindfulness-based intervention or a social support control group of the same duration and dose . Blood pressure was measured with the Omron automatic blood pressure machine at baseline and at the end of the 8-week intervention . A multivariate regression analysis was performed on the difference in scores between baseline and post-intervention blood pressure measurements , controlling for age , education , smoking status , and anti-hypertensive medication use . Effect sizes were calculated to quantify the magnitude of the relationship between participation in the mindfulness-based intervention and the outcome variable , blood pressure . Attendance remained > 80 % in all 8 weeks of both the intervention and the control groups . The average systolic blood pressure decreased for both groups post-intervention . Individuals in the intervention group exhibited a 21.92-mmHg lower systolic blood pressure compared to the social support control group post-intervention and this value was statistically significant ( p = 0.020 ) . The average diastolic blood pressure decreased in the intervention group post-intervention , but increased in the social support group . Individuals in the intervention group exhibited a 16.70-mmHg lower diastolic blood pressure compared to the social support group post-intervention , and this value was statistically significant ( p = 0.003 ) . Older adults are at a time in life when a reflective , stationary intervention , delivered in residence , could be an appealing mechanism to improve blood pressure . Given our preliminary results , larger trials in this hypertensive study population are warranted CONTEXT Psychological distress is linked with impaired glycemic control among diabetics . OBJECTIVE Estimate changes in glycemic control , weight , blood pressure , and stress-related psychological symptoms in patients with type 2 diabetes participating in a st and ard Mindfulness Based Stress Reduction ( MBSR ) program . DESIGN Prospect i ve , observational study . SETTING Academic health center . PATIENTS Adult patients with type 2 diabetes mellitus . INTERVENTIONS Participation in MBSR program for heterogeneous patient population . Diet and exercise regimens held constant . MAIN OUTCOME MEASURES Glycosylated hemoglobin A1c ( HA1c ) , blood pressure , body weight , and Symptom Checklist 90-Revised ( anxiety , depression , somatization , and general psychological distress scores ) . RESULTS Eleven of 14 patients completed the intervention . At 1 month follow-up , HA1c was reduced by 0.48 % ( P = .03 ) , and mean arterial pressure was reduced by 6 mmHg ( P = .009 ) . Body weight did not change . A decrease in measures of depression , anxiety , and general psychological distress was observed OBJECTIVE To determine whether a mindfulness-based stress reduction ( MBSR ) intervention is effective for reducing psychosocial distress ( i.e. , depression , psychosocial stress ) and the progression of nephropathy ( i.e. , albuminuria ) and for improving the subjective health status of patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Patients with type 2 diabetes and microalbuminuria were r and omized to a mindfulness-based intervention ( n = 53 ) or a treatment-as-usual control ( n = 57 ) group . The study is design ed to investigate long-term outcomes over a period of 5 years . We present data up to the first year of follow-up ( FU ) . RESULTS At FU , the MBSR group showed lower levels of depression ( d = 0.71 ) and improved health status ( d = 0.54 ) compared with the control group . No significant differences in albuminuria were found . Per- protocol analysis also showed higher stress reduction in the intervention group ( d = 0.64 ) . CONCLUSIONS MBSR intervention achieved a prolonged reduction in psychosocial distress . The effects on albuminuria will be followed up further Summary : Heart disease is the leading cause of death among Americans each year , yet the misperception still exists that cardiovascular disease is not a serious health problem for women . Evidence indicates that anxiety contributes to the development of heart disease . The primary purpose of this study was to assess the effectiveness of Kabat-Zinn 's mindfulness-based stress reduction program to reduce anxiety in women with heart disease . Anxiety , emotional control , coping styles , and health locus of control were compared in a treatment and control group of women with heart disease . Post-intervention analyses provide initial support for beneficial effects of this program In this study effects of a brief mindfulness-based stress reduction intervention were examined in cardiac patients who had a percutaneous coronary intervention ( PCI ) . One-hundred- and -fourteen patients ( mean age 55 ± 7 years , 18 % women ) were r and omly assigned to a 4-session mindfulness group intervention or a minimal mindfulness self-help control group that received a booklet containing identical information . Compared to self-help , the group intervention showed larger increases in psychological and social quality of life ( p < .05 , partial η2 = .04 and .05 , respectively ) . For symptoms of anxiety and depression , and for perceived stress , this effect was evident only in patients younger than 60 years ( p < .01 , partial η2 = .10 and .15 , respectively ) . These effects were partially or fully mediated by increase in mindfulness . The brief group mindfulness intervention seems beneficial for cardiac PCI patients regarding general psychosocial quality of life , although for specific psychological symptoms , this intervention can be recommended only for nonelderly patients OBJECTIVE Stress has been cited as a causal factor in heart disease . The objective of this study was to examine the effects of an 8-week mindfulness-based stress-reduction program on the resting levels of stress hormones , physical functioning , and submaximal exercise responses in women with heart disease . SUBJECTS R and om selection with the numbers 1 and 2 were used to assign 18 women ( 60 + /-6.3 years old ) with documented histories of heart disease to a treatment group ( n = 9 ) or a control group ( n = 9 ) . Speilberger 's state anxiety scores for the treatment ( M = 37.88 ; st and ard deviation ( SD ) = 10.91 ) and control group ( M = 43.22 ; SD = 12.26 ) were not significantly different prior to the start of the study . However , their scores fell in the upper percentile rank for normal adults in their age category . INTERVENTION The intervention was provided one night each week for 2 hours over a period of 8 weeks . The intervention included didactic , inductive , and experiential modes of learning regarding stress responses and mindfulness skill-development training . DESIGN Pre-post test hormonal measurements and physical function were analyzed using a 2 ( group ) by 2 ( time ) analysis of variance ( ANOVA ) with repeated measures following the 8-week program . Submaximal exercise responses were also compared between the treatment group and the control group following the 8-week program . A 2 ( group ) by 3 ( time ) ANOVA with repeated measures was used to analyze the data . SETTING S/LOCATION Weekly meetings were held on a university medical school campus . Submaximal exercise responses were recorded while participants cycled on a stationary bike in an applied physiology laboratory following the 8-week program . RESULTS There were no significant main effects or interaction for the resting levels of stress hormones or physical functioning . There were no significant interactions for the submaximal exercise responses , however , there were significant main effects between groups for ventilation [ F(2,32 ) = 7.65 , p < .01 , f = 0.8 ] , and between group [ F(1,16 ) = 8.84 , p < .01 , f = 0.8 ] and time [ F(2,32 ) = 10.42 , p < .01 , f = 0.9 ] , for breathing frequency . CONCLUSION While the 8-week stress reduction program for women with heart disease did not show significant interactions between groups for resting levels of stress hormones , physical functioning , or submaximal exercise responses , there was a significant difference in breathing patterns between the 2 groups during exercise following the mindfulness-based stress-reduction program . There was also a trend for change in the intervention group in the resting levels of cortisol and physical function scores that was not seen in the control group . Future studies could use the effect size generated from this pilot study to calculate the number of subjects needed for adequate power to detect significant differences between groups Objective : Patients who suffer from mental fatigue after a stroke or traumatic brain injury ( TBI ) have a drastically reduced capacity for work and for participating in social activities . Since no effective therapy exists , the aim was to implement a novel , non-pharmacological strategy aim ed at improving the condition of these patients . Methods : This study tested a treatment with mindfulness-based stress reduction ( MBSR ) . The results of the programme were evaluated using a self- assessment scale for mental fatigue and neuropsychological tests . Eighteen participants with stroke and 11 with TBI were included . All the subjects were well rehabilitated physically with no gross impairment to cognitive functions other than the symptom mental fatigue . Fifteen participants were r and omized for inclusion in the MBSR programme for 8 weeks , while the other 14 served as controls and received no active treatment . Those who received no active treatment were offered MBSR during the next 8 weeks . Results : Statistically significant improvements were achieved in the primary end-point — the self- assessment for mental fatigue— and in the secondary end-point — neuropsychological tests ; Digit Symbol-Coding and Trail Making Test . Conclusion : The results from the present study show that MBSR may be a promising non-pharmacological treatment for mental fatigue after a stroke or TBI |
1,628 | 21,734,319 | AVGs are capable of generating EE in youth to attain PA guidelines .
Few studies have assessed sustainability of AVG play , which appears to diminish after a short period of time for most players . | BACKGROUND A population level increase in physical activity ( PA ) is critical to reduce obesity in youth .
Video games are highly popular and active video games ( AVGs ) have the potential to play a role in promoting youth PA . | PURPOSE The study evaluated whether targeted changes in factors influencing enjoyment of physical education ( PE ) , physical activity enjoyment , and self-efficacy beliefs about participating in physical activity mediated the effect of the Lifestyle Education for Activity Program ( LEAP ) intervention on participation in physical activity . METHODS High schools ( N=24 ) paired on enrollment size , racial composition , urban or rural location , and class structure were r and omized into control ( N=12 ) or experimental ( N=12 ) groups . Of the 4044 girls enrolled and eligible , 2087 ( 51.6 % ) participated in the measurement component of the study . There were 1038 girls in the control group and 1049 girls in the experimental group . INTERVENTION LEAP was a comprehensive school-based intervention emphasizing changes in instruction and school environment design ed to increase physical activity among black and white adolescent girls . It was organized according to the Coordinated School Health Program and included a PE component with core objectives of promoting enjoyment of PE , physical activity enjoyment , and self-efficacy . RESULTS Latent variable structural equation modeling indicated that : 1 ) the intervention had direct , positive effects on physical activity and factors influencing enjoyment of PE , which subsequently explained the effects of increased physical activity enjoyment and self-efficacy on increased physical activity ; and 2 ) an additional , indirect effect of physical activity enjoyment on physical activity operated by an influence on self-efficacy . CONCLUSIONS Increases in enjoyment partially mediated the positive effect of the LEAP intervention . To our knowledge , we have provided the first experimental evidence from a r and omized controlled trial linking increased enjoyment with increased physical activity among black and white adolescent girls The primary objective of this pilot study was to evaluate the effect of active video games on children 's physical activity levels . Twenty children ( mean ± SD age = 12 ± 1.5 years ; 40 % female ) were r and omised to receive either an active video game up grade package or to a control group ( no intervention ) . Effects on physical activity over the 12-week intervention period were measured using objective ( Actigraph accelerometer ) and subjective ( Physical Activity Question naire for Children [ PAQ-C ] ) measures . An activity log was used to estimate time spent playing active and non-active video games . Children in the intervention group spent less mean time over the total 12-week intervention period playing all video games compared to those in the control group ( 54 versus 98 minutes/day [ difference = -44 minutes/day , 95 % CI [ -92 , 2 ] ] , p = 0.06 ) . Average time spent in all physical activities measured with an accelerometer was higher in the active video game intervention group compared to the control group ( difference at 6 weeks = 194 counts/min , p = 0.04 , and at 12 weeks = 48 counts/min , p = 0.06).This preliminary study suggests that playing active video games on a regular basis may have positive effects on children 's overall physical activity levels . Further research is needed to confirm if playing these games over a longer period of time could also have positive effects on children 's body weight and body mass index . Trial Registration Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists OBJECTIVE We examined the feasibility of Dance Dance Revolution ( DDR ) , a dance video game , in participants ' homes , to increase physical activity ( PA ) and to decrease sedentary screen time ( SST ) . METHODS AND PROCEDURES Sixty children ( 7.5 + /- 0.5 years ) were r and omized in a 2:1 ratio to DDR or to wait-list control ( 10-week delay ) . DDR use was logged , PA was measured objective ly by accelerometry . SST was self-reported at weeks 0 and 10 . At week 28 , after both groups had access to DDR , accelerometry and SST were repeated . RESULTS Mean use of DDR was 89 + /- 82 ( range 0 - 660 min ) min per week ( mpw ) . The DDR group showed increased vigorous PA and a reduction in light PA ; the control group showed no increase in moderate and /or vigorous PA ( MVPA ) although they also had a reduction in light PA . Differences between the groups were not observed . The DDR group also reported a decrease in SST of -1.2 + /- 3.7 h per week ( hpw ) ( P < 0.05 ) , whereas the controls reported an increase of + 3.0 + /- 7.7 hpw ( nonsignificant ) . The difference in SST between the groups was significant , with less SST in the DDR group . Between weeks 10 and 28 , numeric reductions in SST were reported in both groups . In the DDR group , SST at week 28 ( 8.8 + /- 6.0 hpw ) was lower than baseline ( 10.5 + /- 5.5 hpw ; P < 0.03 ) . DISCUSSION This pilot study suggests that DDR reduces SST and may facilitate slight increases in vigorous PA . Further study is needed to better characterize children and context s in which DDR may promote a healthy lifestyle The purpose of this pilot study was to evaluate the effect of a weekly multiplayer class on the motivation of children aged 9 - 12 years to play an interactive dance simulation video game ( IDSVG ) at home over a period of 12 weeks . A sample of 27 children was r and omly assigned to ( 1 ) a home group instructed to play the IDSVG at home ; ( 2 ) a multiplayer group instructed to play the IDSVG at home and to participate in a weekly IDSVG multiplayer class . Participants were asked to play the IDSVG as often as they liked and report the playing time daily on a calendar for a 12-week period . Motivation to play was assessed by the playing duration of IDSVG in minutes and the dropout during the study . Mean age of the 16 children who completed the study was 10.6+/-0.8 years . During the 12-week intervention period , the multiplayer group played approximately twice as many minutes ( 901min ) as the home group ( 376min , p=0.13 ) . Dropout was significantly ( p=0.02 ) lower in the multiplayer group ( 15 % ) than in the home group ( 64 % ) . Our findings suggest that multiplayer classes may increase children 's motivation to play interactive dance simulation video games PURPOSE The primary aim was to determine the energy expenditure ( EE : kcal.kg(-1).h(-1 ) ) in terms of caloric cost and metabolic equivalents of activities commonly performed by children and adolescents . Secondary aims were to determine at what age and pubertal developmental stage values approach those of adults . METHODS In this descriptive study , 295 volunteer youth 8 - 18 yr of age completed 18 common physical activities ( including rest ) while EE was measured continuously with a portable metabolic system . Three sets of activities were assigned in r and om order for each subject . Activities ranged from television viewing and video game play to running and rope skipping . Pubertal development was estimated from a self-report question naire . RESULTS At rest , VO(2 ) and EE were highest in the youngest children and decreased with advancing age and higher pubertal stage in both genders . The age-adjusted and puberty-adjusted energy expenditure values were generally lower than the compendium MET values for sedentary and moderate activities but were more varied for high-intensity activities . However , the ratio of activity EE to REE was comparable in children and adults . CONCLUSIONS Energy expenditure per kilogram of body mass at rest or during exercise is greater in children than adults and varies with pubertal status , thus using the definition of a MET in the compendium of physical activities without adjustment is inadequate for energy estimation in children , until a child reaches Tanner Stage 5 . However , the ratio of activity EE to resting EE in children appears to be similar or slightly less than in the compendium , suggesting that the compendium MET increments used with our adjusted EE values more closely approximate the true EE of activities in children than present adult norms |
1,629 | 20,430,755 | In this study hyperglycaemia in the setting of an acute stroke was transient in the majority of patients | BACKGROUND Non-diabetic patients presenting with an acute stroke often have hyperglycaemia .
In most population s it is unknown whether the hyperglycaemia is transient and due to the acute stress response or whether it represents undiagnosed abnormal glucose metabolism .
AIM To evaluate the prevalence and predictors of persistent hyperglycaemia in non-diabetic patients with an acute stroke . | BACKGROUND AND PURPOSE Hyperglycemia at the time of ischemic stroke is associated with increased mortality and morbidity . Animal studies suggest that infa rct expansion may be responsible . The influence of persisting hyperglycemia after stroke has not previously been examined . We measured the blood glucose profile after acute ischemic stroke and correlated it with infa rct volume changes using T2- and diffusion-weighted MRI . METHODS We recruited 25 subjects within 24 hours of ischemic stroke symptoms . Continuous glucose monitoring was performed with a glucose monitoring device ( CGMS ) , and 4-hour capillary glucose levels ( BGL ) were measured for 72 hours after admission . MRI and clinical assessment s were performed at acute ( median , 15 hours ) , subacute ( median , 5 days ) , and outcome ( median , 85 days ) time points . RESULTS Mean CGMS glucose and mean BGL glucose correlated with infa rct volume change between acute and subacute diffusion-weighted MRI ( r > or=0.60 , P<0.01 ) , acute and outcome MRI ( r=0.56 , P=0.01 ) , outcome National Institutes of Health Stroke Scale ( NIHSS ; r > or=0.53 , P<0.02 ) , and outcome modified Rankin Scale ( mRS ; r > or=0.53 , P=0.02 ) . Acute and final infa rct volume change and outcome NIHSS and mRS were significantly higher in patients with mean CGMS or mean BGL glucose > or=7 mmol/L. Multiple regression analysis indicated that both mean CGMS and BGL glucose levels > or=7 mmol/L were independently associated with increased final infa rct volume change . CONCLUSIONS Persistent hyperglycemia on serial glucose monitoring is an independent determinant of infa rct expansion and is associated with worse functional outcome . There is an urgent need to study normalization of blood glucose after stroke BACKGROUND diabetes mellitus not only increases the risk of ischaemic stroke two- to four-fold but also adversely inXuences prognosis . The prevalence of recognised diabetes mellitus in acute stroke patients is between 8 and 20 % , but between 6 and 42 % of patients may have undiagnosed diabetes mellitus before presentation . Post-stroke hyperglycaemia is frequent and of limited diagnostic value and the oral glucose tolerance test assumes that the patient is clinical ly stable and eating normally . There is a need for a simple and reliable method to predict new diabetes mellitus in acute stroke patients . OBJECTIVES to determine the prevalence of unrecognised diabetes mellitus and impaired glucose tolerance on hospital admission and 12 weeks later in acute stroke patients with post-stroke hyperglycaemia > or = 6.1 mmol/l . To measure the accuracy of hyperglycaemia and elevated glycosylated haemoglobin concentration in predicting the presence of unrecognised diabetes mellitus at 12 weeks . DESIGN acute ( < 24 hours ) stroke patients ( cerebral infa rct ion and primary intracerebral haemorrhage ) with admission hyperglycaemia between 6.0 and 17 mmol/l and without a previous history of insulin-treated diabetes mellitus who were r and omised into the Glucose Insulin in Stroke Trial between October 1997 and May 1999 were studied . The Glucose Insulin in Stroke Trial is a r and omised controlled trial investigating the benefits of maintaining euglycaemia in acute stroke patients with mild to moderate hyperglycaemia . At 12 weeks , survivors underwent a 75 g oral glucose tolerance test . The positive predictive value and negative predictive value of admission plasma glucose > or = 6.1 mmol/l and elevated glycosylated haemoglobin concentration in predicting the presence of diabetes mellitus were used to estimate the prevalence of unrecognised diabetes mellitus in a consecutive series of 582 acute stroke admissions . RESULTS 582 consecutive acute stroke patients were assessed for eligibility for the Glucose Insulin Stroke Trial , of whom 83 ( 14 % ) had recognised diabetes mellitus . One hundred and forty-two patients were r and omised and 62 underwent a 3-month oral glucose tolerance test , of whom 26 ( 42 % ) had normal glucose tolerance , 23 ( 37 % ) had impaired glucose tolerance and 13 ( 21 % ) had diabetes mellitus . Admission plasma glucose > or = 6.1 mmol/l and glycosylated haemoglobin > or = 6.2 % predicted the presence of previously unrecognised diabetes mellitus at 12 weeks with a positive predictive value of 80 % and negative predictive value of 96 % . The estimated prevalence of unrecognised diabetes mellitus in the total series of acute stroke admissions was 16 - 24 % . CONCLUSIONS one-third of all acute stroke patients may have diabetes mellitus . For patients presenting with post-stroke hyperglycaemia , impaired glucose tolerance or diabetes mellitus is present in two-thirds of survivors at 12 weeks . Admission plasma glucose > or = 6.1 mmol/l combined with glycosylated haemoglobin > or = 6.2 % are good predictors of the presence of diabetes mellitus following stroke In a prospect i ve study to correlate admission glucose level with neurologic outcome in stroke , 252 acute stroke patients without prior disability and admitted within 24 hours of onset of ictus were assessed . The stroke was classified into one of three types -- cortical infa rct , lacunar infa rct , or intracerebral hemorrhage -- by clinical , computed tomographic , and necropsy findings . Fifty-one diabetic patients were excluded from the entire cohort to form a nondiabetic category for analysis . We found that admission glucose level showed a significantly higher degree of correlation with mortality and morbidity ( measured as arm function , leg function , and activities of daily living ) when cortical ( n = 118 ) and lacunar ( n = 58 ) infa rcts were pooled compared with when they were assessed separately . For intracerebral hemorrhage ( n = 76 ) , admission glucose level correlated with mortality but not morbidity . This trend persisted despite exclusion of diabetic patients . These results are consistent with previous observations of a correlation between a high admission glucose level and the severity of stroke . The importance of segregating cortical from lacunar infa rcts , two groups with a different natural history and prognosis , in any future analysis is emphasized From August 1987 through December 1989 all consecutive conscious patients younger than 70 years with a recent ( less than 48 h ) brain infa rct ion of the carotid territory were prospect ively included in the study . Blood sample s for fasting blood glucose and glycosylated haemoglobin ( HbA1c ) were taken after a median delay of 23 h of the onset of symptoms . The severity of hemiparesis was assessed on admission , at 1 week , 3 weeks , and 3 months . The functional outcome was assessed at 3 months . Computed cerebral tomography was performed on admission , and later on at 3 weeks or 3 months . The brain infa rct volume was measured from the CTs . The patients were diagnosed to have prestroke normoglycemia ( n = 76 ) and prestroke hyperglycemia ( n = 23 ) on basis of the HbA1c level . The case fatality rate , severity of hemiparesis , functional outcome , and infa rct size did not differ between these 2 groups . On the other h and , fasting blood glucose level of the non-diabetics correlated strongly with the severity of hemiparesis and predicted stroke outcome . A statistically significant correlation was observed between blood glucose values and the volumes of cortical infa rcts in non-diabetics . Because prestroke blood glucose level , in contrast to post-stroke blood glucose level , did not have any predictive value concerning stroke outcome it is concluded that high fasting blood glucose values after stroke reflect a stress response to a more severe ischemic brain lesion BACKGROUND The adrenal glucocorticoid stress response in humans causes catabolism , increasing blood glucose and heart rate , and possibly potentiates ischaemic damage to neurons . These effects could induce secondary brain damage in acute stroke . MATERIAL S AND METHODS This prospect i ve study was based on a single determination of s-cortisol in 172 patients included within 24 h of stroke onset , 50 % within 12 h of stroke onset . All patients were admitted to hospital within 6 h of stroke onset . We investigated the relations of s-cortisol to neurological deficit measured by Sc and inavian Stroke Scale ( SSS ) , lesion volume on CT-scan , blood glucose on admission , pulse rate , blood pressure , body temperature , deteriorating stroke , cytokines and cytokine receptors , and outcome . RESULTS In a multivariate logistic regression analysis , s-cortisol was independently related to death within 7 days of stroke onset , odds ratio ( OR ) Cortisol(+100 nmol/l ) 1.9 ( 95 % CI 1.01 - 3.8 ) ; serum-cortisol was , however , not a predictor of death or dependency within 3 months . S-cortisol correlated to SSS ( rho=-0.45 , p<0.001 ) , body temperature ( rho=0.27 , p<0.001 ) , pulse rate ( rho=0.26 , p<0.001 ) , and lesion volume ( rho=0.33 , p<0.001 ) . S-cortisol was related to the presence of insular damage . CONCLUSION Acute stroke mortality related to increasing serum-cortisol levels . S-cortisol was associated with stroke severity and markers reflecting stroke severity Background Screening for undiagnosed diabetes in patients with acute myocardial infa rct ion is recommended ( ESC and EASD Task Force 2007 ) . Glucose tolerance testing in the peri-infa rct period may not be valid because of confounding , e.g. by the acute stress reaction . The aim was to evaluate undiagnosed diabetes ( DM ) and impaired glucose regulation ( IGR ) in AMI during hospital stay and 3 months after discharge . Material s and methods In 96 consecutively admitted AMI patients ( Heart Center Wuppertal , Germany ) OGTT were performed , of whom in 62 OGTT were also carried out 3 months later . Results Before discharge 32 % of the patients had newly diagnosed diabetes and 47 % patients had prediabetes ( IGR ) . Glucose tolerance was normal in 20 ( 21 % ) patients only . After 3 months , 74 % with newly diagnosed DM at baseline still had disturbed glucose metabolism ( 58 % DM , 16 % IGT ) . No patient with normal OGTT became diabetic after 3 months . In multivariate regression , the odds of having diabetes ( 3 months ) was about sixfold higher when having diabetes before discharge ( OGTT ) . Admission glucose , infa rct ion size CKMAX , and inflammation ( CRP ) were not significantly related to OGTT results . Conclusions This prospect i ve study confirms a high prevalence of undiagnosed DM in patients with AMI . In about 60 % of AMI patients , newly diagnosed DM persisted after 3 months . For the first time we could show that there is no correlation between infa rct ion size and undiagnosed diabetes . Thus , an OGTT performed before discharge may provide a reliable measure of disturbed glucose regulation but needs to be repeated AIMS To assess the cardiovascular disease ( CVD ) risk of people with screen-detected Type 2 diabetes and to estimate the risk reduction achievable through early intensive pharmacological intervention . METHODS In ADDITION-Cambridge , diabetic patients were identified among people aged 40 - 69 years through a stepwise screening procedure including a risk score , r and om and fasting capillary blood glucose , HbA(1c ) and oral glucose tolerance test . In those without prior macrovascular disease , 10-year CVD risk was computed using UK Prospect i ve Diabetes Study ( UKPDS ) and Framingham engines . The absolute risk reduction achievable and its plausible range were predicted using relative risk reductions for individual therapies from published trials and sensitivity analysis . RESULTS Of the 867 individuals with undiagnosed diabetes , 19 % had pre-existing CVD , 97 % were overweight or obese , 86 % had hypertension , 75 % had dyslipidaemia , 20 % had microalbuminuria and 18 % were smokers . Of those with hypertension , 35 % were not prescribed drugs and 42 % were suboptimally treated . Of participants with dyslipidaemia , 68 % were not prescribed medications and 22 % were poorly controlled . Median 10-year CVD risk was 34.0%[interquartile range ( IQR ) 26.2 - 44.6 ] in men and 21.5 % ( IQR 15.7 - 28.7 ) in women using the UKPDS engine ; 38.6 % ( IQR 27.8 - 53.0 ) in men and 24.6 % ( IQR 17.2 - 32.9 ) in women using Framingham equations . In the most conservative scenario ( no additive effect of therapies ) , the absolute risk reduction achievable through multifactorial therapy ranged from 4.9 to 9.5 % ( UKPDS ) and from 5.4 to 10.5 % ( Framingham ) . The corresponding ranges of numbers needed to treat were 11 - 20 and 10 - 19 . CONCLUSIONS People with screen-detected diabetes have an adverse cardiovascular risk profile , which is potentially modifiable through application of existing treatment recommendations BACKGROUND Hyperglycaemia after acute stroke is a common finding that has been associated with an increased risk of death . We sought to determine whether treatment with glucose-potassium-insulin ( GKI ) infusions to maintain euglycaemia immediately after the acute event reduces death at 90 days . METHODS Patients presenting within 24 h of stroke onset and with admission plasma glucose concentration between 6.0 - 17.0 mmol/L were r and omly assigned to receive variable-dose-insulin GKI ( intervention ) or saline ( control ) as a continuous intravenous infusion for 24 h. The purpose of GKI infusion was to maintain capillary glucose at 4 - 7 mmol/L , with no glucose intervention in the control group . The primary outcome was death at 90 days , and the secondary endpoint was avoidance of death or severe disability at 90 days . Additional planned analyses were done to determine any differences in residual disability or neurological and functional recovery . The trial was powered to detect a mortality difference of 6 % ( sample size 2355 ) , with 83 % power , at the 5 % two-sided significance level . This study is registered as an International St and ard R and omised Controlled Trial ( number IS RCT N 31118803 ) FINDINGS The trial was stopped due to slow enrolment after 933 patients were recruited . For the intention-to-treat data , there was no significant reduction in mortality at 90 days ( GKI vs control : odds ratio 1.14 , 95 % CI 0.86 - 1.51 , p=0.37 ) . There were no significant differences for secondary outcomes . In the GKI group , overall mean plasma glucose and mean systolic blood pressure were significantly lower than in the control group ( mean difference in glucose 0.57 mmol/L , p<0.001 ; mean difference in blood pressure 9.0 mmHg , p<0.0001 ) . INTERPRETATION GKI infusions significantly reduced plasma glucose concentrations and blood pressure . Treatment within the trial protocol was not associated with significant clinical benefit , although the study was underpowered and alternative results can not be excluded |
1,630 | 26,543,067 | Evidence is strongest for the use of simulation and competency-based paradigms in teaching procedures , and these approaches should be the mainstay of programmes that train physicians to perform procedures . | IMPORTANCE Optimal approaches to teaching bedside procedures are unknown .
OBJECTIVE To identify effective instructional approaches in procedural training . | Background : Previous studies have described that pediatric offices are ill-prepared for medical emergencies . Pediatric " mock codes " have been utilized to increase the emergency preparedness of inpatient medical units for several decades . These practice drills have been shown to both increase practitioners ' confidence and decrease anxiety during actual resuscitations . Although the use of mock codes is recommended in the outpatient setting , these benefits have yet to be demonstrated for office-based practitioners . Objective : We conducted this study to determine whether mock codes performed in pediatric primary care offices increase practitioner confidence to perform life-saving skills . Methods : Pediatric group practice s participated in a clinical trial of an office-based , 2-step , emergency preparedness training . First , physicians and staffs attended a 1-hour didactic program which included staff education , office emergency protocol s , emergency equipment and medications , and guidelines on instituting a mock code program . Second , each practice participated in a 10 - 15-minute mock code exercise . The drill was conducted by pediatric advanced life support instructors . After the code , a 30-minute feedback session was conducted which review ed office coordination , individual skill performance , and approach to resuscitation . Each participating practice also received an infant manikin and a text complete with several mock codes scenarios written specifically for the pediatric primary care office . Evaluation of the intervention consisted of 2 components . ( 1 ) Pre- and postintervention completion of a self-administered survey assessed participants ' comfort in emergency situations and confidence to perform specific life-saving skills , using an ordinal scale : 1 = " strongly agree " to 5 = " strongly disagree " . ( 2 ) Practice s were contacted by telephone 12 months after the training to determine whether they had implemented improvements in emergency preparedness , including instituting mock codes , preparing a written emergency protocol and purchasing new emergency equipment and medications . Results : Eleven group pediatric practice s participated , which were representative of urban , suburban , and rural offices in southwestern Pennsylvania . Ninety-seven of a total 164 ( 59 % ) physicians and staff members completed both pre- and postintervention surveys . Practitioner participants were analyzed in 2 groups . Group 1 consisted of physicians , nurse practitioners , and physician assistants ; group 2 consisted of registered nurses , licensed practical nurses , and medical assistants . Comparison of pre- versus postintervention surveys in both of these groups revealed significant improvement in reported confidence to perform resuscitation skills that were included in the mock code after the training : airway positioning ( group 1 , 67 % vs. 94 % , P < 0.001 ; group 2 , 55 % vs. 75 % , P = 0.003 ) , airway suctioning , ( group 1 , 64 % vs. 88 % , P = 0.005 ; group 2 , 27 % vs. 51 % , P < 0.001 ) , and bag-mask assisted ventilation ( group 1 , 82 % vs. 91 % , P = 0.003 ; group 2 , 39 % vs. 71 % , P < 0.001 ) . In addition , group 1 reported more confidence in their ability to place an intraossesous line ( 24 % vs. 39 % , P = 0.003 ) and group 2 showed a significant increase in their confidence to administer oxygen ( 65 % vs. 84 % , P < 0.001 ) . As a result of the mock code , 83 % of all participants , both medical and nonmedical staffs , and 96 % of physicians felt less anxious about medical emergencies in the office . Twelve months after the conclusion of the program , 18 % of offices had conducted 1 or more mock codes , 64 % of offices had written an emergency protocol , and 27 % of offices had acquired essential resuscitation medications or equipment . Conclusions : The results of this study support the recommendation that mock codes should be performed in the pediatric primary care setting to improve practitioner confidence and decrease practitioner anxiety Background Benefits of skills lab training are widely accepted , but there is sparse research on its long-term effectiveness . We therefore conducted a prospect i ve , r and omised controlled-trial to investigate whether in a simulated setting students trained according to a " best practice " model ( BPSL ) perform two skills of different complexity ( nasogastral tube insertion , NGT ; intravenous cannulation , IVC ) better than students trained with a traditional " see one , do one " teaching approach ( TRAD ) , at follow-up of 3 or 6 months . Methodology and Principal Findings 94 first-year medical students were r and omly assigned to one of four groups : BPSL training or TRAD teaching with follow-up at 3 ( 3 M ) or 6 ( 6 M ) months . BPSL included structured feedback , practice on manikins , and Peyton ’s " Four-Step-Approach " , while TRAD was only based on the " see one - do one " principle . At follow-up , manikins were used to assess students ’ performance by two independent blinded video-assessors using binary checklists and a single-item global assessment scale . BPSL students scored significantly higher immediately after training ( NGT : BPSL3 M 94.8%±0.2 and BPSL6 M 95.4%±0.3 percentage of maximal score ± SEM ; TRAD3 M 86.1%±0.5 and TRAD6 M 84.7%±0.4 . IVC : BPSL3 M 86.4%±0.5 and BPSL6 M 88.0%±0.5 ; TRAD3 M 73.2%±0.7 and TRAD6 M 72.5%±0.7 ) and lost significantly less of their performance ability at each follow-up ( NGT : BPSL3 M 86.3%±0.3 and TRAD3 M 70.3%±0.6 ; BPSL6 M 89.0%±0.3 and TRAD6 M 65.4%±0.6 ; IVC : BPSL3 M 79.5%±0.5 and TRAD3 M 56.5%±0.5 ; BPSL6 M 73.2%±0.4 and TRAD6 M 51.5%±0.8 ) . In addition , BPSL students were more often rated clinical ly competent at all assessment times . The superiority at assessment after training was higher for the more complex skill ( IVC ) , whereas NGT with its lower complexity profited more with regard to long-term retention . Conclusions This study shows that within a simulated setting BPSL is significantly more effective than TRAD for skills of different complexity assessed immediately after training and at follow-up . The advantages of BPSL training are seen especially in long-term retention BACKGROUND AND OBJECTIVE : Simulation-based medical education ( SBME ) is used to teach residents . However , few studies have evaluated its clinical impact . The goal of this study was to evaluate the impact of an SBME session on pediatric interns ’ clinical procedural success . METHODS : This r and omized trial was conducted at 10 academic medical centers . Interns were surveyed on infant lumbar puncture ( ILP ) and child intravenous line placement ( CIV ) knowledge and watched audiovisual expert modeling of both procedures . Participants were r and omized to SBME mastery learning for ILP or CIV and for 6 succeeding months reported clinical performance for both procedures . ILP success was defined as obtaining a sample on the first attempt with < 1000 red blood cells per high-power field or fluid described as clear . CIV success was defined as placement of a functioning catheter on the first try . Each group served as the control group for the procedure for which they did not receive the intervention . RESULTS : Two-hundred interns participated ( 104 in the ILP group and 96 in the CIV group ) . Together , they reported 409 procedures . ILP success rates were 34 % ( 31 of 91 ) for interns who received ILP mastery learning and 34 % ( 25 of 73 ) for controls ( difference : 0.2 % [ 95 % confidence interval : –0.1 to 0.1 ] ) . The CIV success rate was 54 % ( 62 of 115 ) for interns who received CIV mastery learning compared with 50 % ( 58 of 115 ) for controls ( difference : 3 % [ 95 % confidence interval : –10 to 17 ] ) . CONCLUSIONS : Participation in a single SBME mastery learning session was insufficient to affect pediatric interns ’ subsequent procedural success OBJECTIVE To evaluate the effectiveness of an educational intervention on pediatric residents ' resuscitation fund of knowledge , technical skills , confidence , and overall performance . DESIGN Prospect i ve , nonconcurrent , controlled interventional trial . SETTING Urban pediatric tertiary care hospital . PARTICIPANTS An intervention group ( IG ) of 28 pediatric residents graduating in 1997 , and a control group ( CG ) of 30 pediatric residents graduating in 1996 . INTERVENTIONS Resuscitation course with didactic lectures and skills practice stations , as well as a minimum of 3 practice mock resuscitations with immediate feedback throughout postgraduate year 3 . MAIN OUTCOME MEASURES Fund of knowledge , using the Pediatric Advanced Life Support test and short answer test ; technical skills , using the Airway and Vascular Access Skills Assessment ; experience and confidence , using an anonymous survey ; and overall performance , evaluated using a videotaped mock resuscitation test . RESULTS The IG scored better on the short answer test ( P<.001 ) . A larger number of IG residents were successful in the completion of ancillary airway maneuvers and femoral vascular access ( P = .02 ) , as well as endotracheal intubation ( P = .004 ) and intraosseous access ( P = .002 ) . The IG was more confident in their leadership role ( P = .0001 ) and technical skills ( P = .05 ) . Trends toward improved overall performance were noted for the IG mock resuscitations . Residents in the IG were more likely to assess the airway in fewer than 2 minutes ( P = .02 ) , recognize the threat to life in fewer than 5 minutes ( P = .02 ) , and complete the primary survey in a timely fashion ( P = .05 ) . They required fewer prompts ( P = .04 ) and made fewer mistakes ( P = .07 ) . CONCLUSIONS A structured , formal curriculum can improve the necessary fund of knowledge , skills , confidence , and leadership required for resuscitation Background Unsuccessful or traumatic lumbar punctures ( LPs ) occur commonly and contribute to patient discomfort and to challenges in medical decision making in the pediatric emergency department ( ED ) . Objective We produced an instructional video demonstrating the best practice s in pediatric LP technique . We hypothesized that the performance of LPs would change and the rate of successful LPs would increase after watching the video . Methods This was a prospect i ve study of LPs performed in an urban , academic pediatric ED before and after an educational intervention . Lumbar punctures performed during year 1 constituted the control arm . During year 2 , all medical practitioners working in the ED watched the instructional video , and this constituted the interventional arm . The practitioner performing the LP completed a st and ardized data collection form after each LP procedure , and medical records were review ed . Results Data forms were collected on 668 LPs during the study period , 391 during year 1 and 277 during year 2 . There was neither a significant change in overall LP success rate between the 2 years ( 56.8 % year 1 vs 53.4 % year 2 ) nor a significant difference in median number of LP attempts required per patient ( P = 0.78 ) . Seventy-eight percent of participants who viewed the LP video during year 2 stated that the video helped increase their comfort level with performing LPs . The odds of using the techniques endorsed in the educational video were significantly higher during year 2 compared to year 1 for use of local anesthetic , early stylet removal , and vertical patient position . Conclusions The video increased practitioners ’ comfort level with the performance of pediatric LPs and adherence to evidence -based best practice s. It was not associated with an increased rate of successful LPs BACKGROUND We studied the reasons why patients undergoing thoracenteses performed in our outpatient pulmonary clinic had a higher frequency of iatrogenic pneumothorax compared to that in the concurrent radiology practice in our institution , which utilizes ultrasound guidance . We review ed our practice model and implemented a unique experiential training paradigm in a zero-risk simulation environment to improve efficacy , timeliness , service orientation , and safety . METHODS We retrospectively determined the rate of clinical ly significant pneumothoraces in our practice ( phase I , July 1 , 2001 , to June 30 , 2002 ) . The training system re design included the following : ( 1 ) a design ated group of pulmonologist instructors dedicated to treating pleural disease and reducing the number of iatrogenic complications ; ( 2 ) the use of ultrasound image guidance for all thoracenteses ; and ( 3 ) structured proficiency and competency st and ards for proceduralists . Postintervention ( phase II ) data were prospect ively collected ( January 2005 to December 2006 ) and compared with our baseline data . RESULTS The baseline rate of pneumothorax was 8.6 % ( 5 of 58 patients ) in our pulmonary practice . Following intervention ( phase II ) , the rate of pneumothorax declined to 1.1 % ( p = 0.0034 ) . During phase II , the number of thoracenteses performed increased ( 186 vs 58 per year , respectively ; p < 0.05 ) . The iatrogenic pneumothorax rate was stable in the 2 years following intervention ( 2005 , 0.7 % [ 1 of 137 pneumothoraces ] ; 2006 , 1.3 % [ 3 of 226 pneumothoraces ] ; p > 0.9 ) . Postintervention complications included procedure-related pain ( n = 19 ) , cough ( n = 4 ) , and hypotension ( n = 10 ) . CONCLUSIONS An improvement program that included simulation , ultrasound guidance , competency testing , and performance feedback reduced iatrogenic risk to patients . We recommend application of this process to procedural practice OBJECTIVES Simulation training offers opportunities for unsupervised , self-regulated learning , yet little evidence is available to indicate the efficacy of this approach in the learning of procedural skills . We evaluated the effectiveness of directed self-regulated learning ( DSRL ) and instructor-regulated learning ( IRL ) , respectively , for teaching lumbar puncture ( LP ) using simulation . METHODS We r and omly assigned internal medicine residents in postgraduate year 1 to either DSRL ( ' directed ' to progress from easy to difficult LP simulators during self-regulated learning ) or IRL ( in groups of four led by an instructor ) . All participants practised for up to 50 minutes and completed a pre-test , post-test and delayed ( by 3 months ) retention test on the simulator . Pairs of blinded trained experts independently rated all videotaped performances using a vali date d global rating scale and a modified version of a vali date d checklist . Participants provided measures of LP experience and self-reported confidence . We analysed the pre-post ( n = 42 ) and pre-post-retention performance scores ( n = 23 ) using two separate repeated- measures analyses of variance ( anovas ) and computed Pearson correlation coefficients between participants ' confidence and performance scores . RESULTS Inter-rater agreement was strong for both performance measures ( intra-class correlation coefficient > 0.81 ) . The groups achieved similar pre-test and post-test scores ( p > 0.05 ) and scores in both groups improved significantly from the pre- to the post-test ( p < 0.05 ) . On retention , a significant interaction ( F(2,42 ) = 3.92 , p = 0.03 ) suggests the DSRL group maintained its post-test performance , whereas that in the IRL group dropped significantly ( p < 0.05 ) . Correlations between self-reported confidence and post-test performance were positive and significant for the DSRL group , and negative and non-significant for the IRL group . CONCLUSIONS Both IRL and DSRL led to improved LP performance immediately after practice . Whereas the IRL group 's skills declined after 3 months , the DSRL group 's performance was maintained , suggesting a potential long-term benefit of this training . Participants in the DSRL group also developed a more accurate relationship between confidence and competence following practice . Further research is needed to clarify the mechanisms of self-regulated learning and its role in simulation context Introduction : Our objective was to establish competency and ensure retention in the steps of the lumbar puncture procedure . Methods : This was a prospect i ve cohort study of first- and second-year emergency medicine residents . Residents completed a survey and then viewed a 5-minute PowerPoint ™ slide presentation and a 15-minute video on performing the procedure . They completed a baseline assessment of competency using a lumbar puncture simulator , received feedback on their performance , and practice d the procedure . They self-recorded the number of practice attempts and performed a second procedure for assessment . Within 3 to 6 months , they performed the procedure for a third observation . The assessment s were performed with the same simulator and directly observed by two raters . A previously vali date d critical actions checklist consisting of 23 critical actions was used . Competency was defined as ≥19 critical actions correct ( > 80 % ) . Inter-rater reliability was examined using the intraclass correlation coefficient [ ICC(2,k ) ] . Results : Seventeen first-year residents and nine second-year residents completed the initial training . Sixteen first-year residents and eight second-year residents completed the retention assessment . An additional four second-year residents were trained several months into their second year . Twelve of 17 first-year residents and 10 of 13 second-year residents demonstrated competence on the baseline evaluation . All residents demonstrated competence after practice ( N = 30 ) and at the retention check ( N = 24 ) . The mean ( SD ) number of practice attempts before the post practice assessment was 3.6 ( 1.1 ) for first years and 2.4 ( 2.3 ) for second years . Conclusions : This study demonstrated the achievement and retention of competency in the steps of the lumbar puncture procedure in a task trainer model Objective : To assess the baseline ability of pediatric residents to successfully perform a lumbar puncture ( LP ) and to evaluate the impact of an educational intervention on this skill in both a simulated and clinical environment . Methods : An experimental group of first-year residents and a control group of second-year residents were enrolled in a prospect i ve nonr and omized intervention study . Knowledge and skill at performing LPs were assessed using a written and a simulated LP test . The experimental group was tested at the start of their residency and then received the educational intervention . They were retested 6 months later . The control group did not receive the educational intervention and were tested at the start of their second year . The outcomes of clinical LPs performed by the 2 groups were also recorded . Results : The experimental group showed significant improvement on both the written and the simulated LP test after the educational intervention . When compared with the control group , they performed the simulated LP significantly better as measured by the number of correctly performed steps . Both groups performed a low number of clinical LPs . Conclusions : After an educational intervention , pediatric first-year residents performed a simulated LP better than a group of second-year residents who had greater clinical LP experience . The low number of clinical LPs performed limits our ability to determine the educational intervention 's impact in the clinical setting and reinforces the concern that recent changes to pediatric residencies may negatively impact residents ' procedural experience Introduction : Recently , efforts have been undertaken to enhance the face validity of technical skills training by introducing role-plays and st and ardised patients . Since little is known about the effects of role-playing with respect to the realism of a training situation and students ’ objective performance , we performed a r and omized controlled trial . Methods : 36 medical students participated in videotaped small group skills-lab sessions on the topics of Doppler sonography and gastric tube insertion . One half of the students participated in role-plays and the other half practised without role-playing . Realism of the training situation was analysed by means of post-intervention self-selected student survey evaluations . Technical performance and patient-physician communication were assessed by independent ratings of the videotaped sessions . Results : The physician 's role was regarded to be significantly more realistic when performing role-plays . Assessment of videotaped sessions showed that practising technical skills by performing role-plays result ed in significantly better patient-physician communication whereas students ’ technical performance did not differ between groups . Conclusion : Introducing role-plays enhances the realism of technical skills training and leads to better patient-physician communication . Students do not seem to be overstrained by practising clinical technical skills using role-plays . We conclude that role-playing is a valuable method in practising technical skills Background and objective The aim of the study was to compare the effectiveness of teaching of general anaesthesia induction to medical students using either full-scale simulation or traditional supervised teaching with patients in the operating theatre . Methods Forty-six fourth year students attending their course in anaesthesiology were enrolled . The students were r and omly assigned to two groups . The simulation group received training in the simulator . The traditional training group was supervised by a senior consultant anaesthetist . After the training sessions all students were tested in the simulator setting . The test was assessed using a 40-item evaluation list . Results Thirty-three per cent of students in the traditional group and 87 % of the students in the simulation group passed the test . Statistically significant differences were : request of glycopyrrolate ( P < 0.001 ) , SpO2 monitoring ( P < 0.001 ) , used gloves when placing an intravenous cannula ( P = 0.012 ) , intubation attempt within 30 s ( P < 0.04 ) , anaesthesia gas set at MAC at least 1 ( P < 0.04 ) , instructed anaesthetic nurse to keep SpO2 at least 95 % ( P < 0.05 ) , keep MAP at least 60 mmHg ( P < 0.05 ) , keep heart rate more than 50 beats per minute ( P < 0.002 ) , keep end-tidal pCO2 4–5.5 kPa ( P < 0.002 ) . Conclusion The simulation group performed better in 25 % of the tasks and similarly in the others compared with the traditional teaching group . With the same time and amount of teaching personnel we trained five or six students in the simulator compared with one student in the operating theatre . Further research will reveal whether these promising results with simulation may be applied more generally in anaesthesiology teaching to medical students Background : Infant lumbar puncture ( LP ) is m and ated by the Accreditation Council for Graduate Medical Education for all pediatric trainees . Current training usually involves the apprenticeship model of “ see one , do one , teach one ” where a trainee 's first LP attempt occurs in a high-stakes environment . Simulation training promotes skill development in a safe environment before patient contact . Objective : To demonstrate that deliberate practice simulation-based training after audiovisual training ( AV ) improves infant LP skills compared with a control group receiving AV training only . Design / Methods : This was a r and omized trial of simulation-based training + AV versus AV only for pediatric residents . On enrollment , the subjects ' infant LP skills were evaluated through their performance on a simulator . A question naire and brief quiz were administered to collect information on the subjects ' infant LP experience , knowledge , and confidence . All subjects viewed an educational AV presentation . The intervention group went on to participate in a simulation-based deliberate practice session on the infant LP simulator while the control group did not . Our primary outcome was self-reported clinical success on the first infant LP after training . Secondary outcomes were rates of traumatic clinical LPs , infant LP skills ( measured via observed structured clinical examinations on the simulator 6 months after training ) , and change in participants ' knowledge and confidence . Results : Fifty-one residents reported 32 clinical encounters . Sixteen of 17 subjects ( 94 % ) in the intervention group who performed a clinical infant LP obtained cerebrospinal fluid compared with 7 of 15 subjects ( 47 % ) in the control group ( difference = 47 % ; 95 % CI = 16%–70 % ) . There was no difference between groups at 6 months on observed structured clinical examination performance , knowledge , or confidence . Conclusions : Participation in a simulation-based deliberate practice intervention can improve infant LP skill CONTEXT The optimal learner to simulator ratio for procedural skills training is not known . Research in motor learning suggests observational training in pairs , termed ' dyad training ' , may be as effective as directed self-regulated learning ( DSRL ) . OBJECTIVES This study was conducted to compare the relative effectiveness and efficiency of dyad versus DSRL training of simulation-based lumbar puncture ( LP ) . METHODS We conducted a two-group r and omised equivalence trial . First-year internal medicine residents ( n = 50 ) were r and omly assigned to learn LP either in dyads or as individual learners on a simulator , using a directed self-regulated approach ( i.e. the learning sequence was defined for them , but they defined the pace of learning ) . Participants were videotaped performing a simulated LP on a pre-test , an immediate post-test , and a 6-week delayed retention test . In duplicate , blinded raters independently evaluated all trainee performances using a previously vali date d 5-point global rating scale ( GRS ) and 35-item checklist . RESULTS Our analyses showed no significant differences ( p = 0.69 ) on pre-test , post-test or retention test GRS scores between the dyad ( mean ± st and ard deviation [ SD ] scores by test : 2.39 ± 0.57 , 3.48 ± 0.62 , 3.12 ± 0.85 , respectively ) and DSRL ( mean ± SD scores by test : 2.67 ± 0.50 , 3.34 ± 0.77 , 3.21 ± 0.79 , respectively ) groups . Both groups improved significantly from pre-test to post-test ( p < 0.001 ) and retained that performance following the 6-week delay . Dyad participants experienced significantly greater pre-test to post-test gains than DSRL participants ( p = 0.02 ) . There was no significant difference in total practice time between the groups ( 20.94 minutes for individuals and 24.20 minutes for dyads ; p = 0.175 ) . CONCLUSIONS Our results indicate that learning in pairs is as effective as independent DSRL . Dyad training permits the more efficient use of simulators as two learners use the same re sources as an individual BACKGROUND Procedure services may improve the training of bedside procedures . However , little is known about how procedure services may affect the dem and for and success of procedures performed on general medicine in patients . OBJECTIVE Determine whether a procedure service affects the number and success of 4 bedside procedures ( paracentesis , thoracentesis , lumbar puncture , and central venous catheterization ) attempted on general medicine in patients . DESIGN Prospect i ve cohort study . SETTING Large public teaching hospital . PATIENTS Nineteen hundred and forty-one consecutive admissions to the general medicine service . INTERVENTION A bedside procedure service was offered to physicians from 1 of 3 firms for 4 weeks . This service then crossed over to physicians from the other 2 firms for another 4 weeks . MEASUREMENTS Data on all procedure attempts were collected daily from physicians . We examined whether the number of attempts and the proportion of successful attempts differed based on whether firms were offered the beside procedure service . RESULTS The number of procedure attempts was 48 % higher in firms offered the service ( 90 versus 61 per 1000 admissions ; RR 1.48 , 95 % CI 1.06 - 2.10 ; P = .030 ) . More than 85 % of the observed increase was a result of procedures with therapeutic indications . There were no differences between firms in the proportions of successful attempts or major complications . CONCLUSIONS The availability of a procedure service may increase the overall dem and for bedside procedures . Further studies should refine the indications for and anticipated benefits from these commonly performed invasive procedures OBJECTIVES /HYPOTHESIS Life-support training emphasizes the primacy of airway management . Acquiring these skills requires practice and exposure to events . Otolaryngology residents lack st and ardized training in advanced airway skills . This project aim ed to create such a program by using simulation-based methodology evaluated using specific educationally based tools . STUDY DESIGN Prospect i ve cohort study . METHODS The program consisted of lectures and simulation-based training sessions design ed to impart competency in a set of defined airway skills to otolaryngology residents . Only participating residents who completed the course ( n = 12 ) were evaluated both before and after the course for their fund of knowledge through multiple-choice examinations and for clinical reasoning and technical skills as assessed by a panel of otolaryngologists in simulated difficult airway situations . Self- assessment tools were also incorporated . RESULTS The average multiple choice score was 12 of 27 ( 44 % ) before the course and 15 of 27 ( 55 % ) after the completion of the course ( P = .001 ) . Faculty assessment yielded a cumulative score of 80 % and 91 % pre- and postcourse , respectively ( P = .002 ) . Although all residents reported prior experience in a critical emergency airway situation , only one reported prior training in advanced airway skills . A significant increase in participants ' self-perceived ability to carry out critical airway-related skills was observed . All respondents felt the course was effective . CONCLUSIONS Simulation-based airway training courses can be effectively incorporated into existing educational curricula for otolaryngology residents , and their success can be measured using educationally based tools . With such a course , residents can be expected to demonstrate measurable improvement in clinical knowledge base , technical skills , and self-perceived ability to h and le difficult airway situations Objective : To determine the frequency of cardiopulmonary resuscitation education using high-fidelity patient simulators during pediatric residency training . Design : R and omized controlled trial . Setting : Suburban tertiary care children 's hospital residency training program . Subjects : Twenty-four second year pediatric residents . Interventions : Twenty-four second year pediatric residents were r and omized into two study groups , 12 residents in each . Both groups completed a formal resuscitation training course utilizing lectures , skill stations , and six scenarios on high-fidelity patient stimulators . Group A was retested on three scenarios 4 months after training and group B was similarly retested 8 months after training . Measurements and Main Results : Time intervals from induction of a clinical problem to its definitive management were recorded for each resident . Residents were also asked to complete surveys following each episode of training and testing . The mean time intervals , for group A , to start effective bag mask ventilation and chest compressions in response to apnea and cardiac arrest were 17.75 secs ( ±3.39 secs ) and 23.42 secs ( ±9.33 secs ) , respectively . These were significantly shorter than 32.7 secs ( ±18.6 secs ) and 81.2 secs ( ±74.9 secs ) , for group B , respectively ( p < .05 ) . Residents in group A provided higher survey scores for their level of confidence in using cardiopulmonary resuscitation pharmacology than residents in group B did ( p < .05 ) . The two groups were no different in their response time to defibrillate or to start anti-arrhythmia medications for life-threatening arrhythmias and in their endotracheal intubation skills . Conclusions : Pediatric residents show a significantly slower response time to effectively manage episodes of apnea and cardiac arrest 8 months after their initial resuscitation training , when compared to 4 months after training . These results may indicate that residents require more frequent training than currently recommended BACKGROUND An in-house produced video compact disc ( VCD ) demonstrating nasogastric intubation was introduced to the medical curriculum at Buddhachinaraj Hospital , Clinical Teaching Centre , Phitsanulok in 2005 . OBJECTIVE The present study aim ed to qualitatively evaluate the effect of the VCD on our medical students ' procedural skills . MATERIAL AND METHOD The 6th year medical students were r and omly allocated into two groups ; one group viewed the VCD ( test , n = 30 ) , and the other group did not ( control , n = 31 ) . After 2 months , the authors examined all students by asking them to perform the procedure using a manikin and a checklist . The examiners were blind to the allocations at the time of examination . Unpaired t-tests and Chi-square tests were used Data are expressed as mean and SD . RESULTS Total checklist 's score was 20 . There was no diference in terms of age or gender between the two groups . Thirty of 61 medical students who had watched the VCD got an average score of 15.9 + /-1.86 , while the control group 's average score was 13.2+/-1.94 . Statistical analyses showed that the difference was significant ( p < 0.0001 ) . CONCLUSION The medical students were able to self-improve their procedural skills of nasogastric intubation after viewing the VCD . Application of this method to other basic procedures may be useful BACKGROUND : Pediatric housestaff are required to learn basic procedural skills and demonstrate competence during training . To our knowledge , an evidence d-based procedural skills curriculum does not exist . OBJECTIVE : To create , implement , and evaluate a modular procedural skills curriculum for pediatric residents . METHODS : A r and omized , controlled trial was performed . Thirty-eight interns in the Boston Combined Residency Program who began their training in 2005 were enrolled and r and omly assigned . Modules were created to teach residents bag-mask ventilation , venipuncture , peripheral intravenous catheter ( PIV ) insertion , and lumbar puncture skills . The curriculum was administered to participants in the intervention group during intern orientation . Interns in the control group learned procedural skills by usual methods . Subjects were evaluated by using a structured objective assessment on simulators immediately after the intervention and 7 months later . Success in performing live-patient procedures was self-reported by subjects . The primary outcome was successful performance of the procedure on the initial assessment . Secondary outcomes included checklist and knowledge examination scores , live-patient success , and qualitative assessment of the curriculum . RESULTS : Participants in the intervention group performed PIV placement more successfully than controls ( 79 % vs 35 % ) and scored significantly higher on the checklist for PIV placement ( 81 % vs 61 % ) and lumbar puncture ( 77 % vs 68 % ) at the initial assessment . There were no differences between groups at month 7 , and both groups demonstrated declining skills . There were no statistically significant differences in success on live-patient procedures . Those in the intervention group scored significantly higher on knowledge examinations . CONCLUSIONS : Participants in the intervention group were more successful performing certain simulated procedures than controls when tested immediately after receiving the curriculum but demonstrated declining skills thereafter . Future efforts must emphasize retraining , and residents must have sufficient opportunities to practice skills learned in a formal curriculum STUDY OBJECTIVES We determine skill acquisition and performance by using a battery-operated , intraosseous needle driver in cadavers . METHODS This was a prospect i ve study of the EZ-IO , a battery-operated intraosseous needle driver ( Vidacare Corp ) . Operators received a 5-minute presentation ( with 1 insertion demonstration ) and then performed 3 tibial insertions on a cadaver . Insertion time was measured from skin placement until stylet removal . Another participant recorded the time and determination of " success . " Success required stable bone position and infusion of fluid without extravasation . After testing , operators completed a question naire including ease of use ( 1 to 5 ; 1=very difficult , 5=very easy ) , speed versus central line ( faster , same , slower ) , ease of use versus a central line ( easier , same , harder ) , and willingness to use the device in future cardiac arrest situations ( yes , maybe , no ) . RESULTS Operators included 42 emergency medicine attending physicians , 13 other physicians , 31 emergency medicine residents , and 13 nonphysicians ( emergency medical services , etc ) . None had previous experience with the EZ-IO , and 80 of 99 ( 80.8 % ) had never placed an intraosseous needle . Two hundred eighty-nine of 297 insertions ( 97.3 % ) were successful . Success rates for the first , second , and third insertion were 96.9 % , 94.9 % , and 100 % , respectively . Median insertion time was 6 seconds ( range 3 to 25 seconds ) , with interquartile range 5 to 8 seconds . The mean ease of use rating was 4.8 ( 95 % confidence interval 4.70 to 4.90 ) . All operators subjectively rated the device faster and easier than a central line ; 98 of 99 ( 99 % ) expressed willingness to use the device in a cardiac arrest . CONCLUSION The EZ-IO requires minimal training , is easy to use , and is fast . Skill acquisition is rapid , with a high success rate on the initial insertion after a brief training session and a single demonstration Background : Although skills-lab training is widely used for training undergraduates in technical procedures , the way in which clinical skills are to be used and instructed remains a matter of debate . Purpose : We conducted a r and omized controlled trial to evaluate the learning outcome of two different instructional approaches in the context of acquiring procedural – technical skills . Methods : Volunteer 2nd- and 3rd-year medical students were r and omly assigned to an intervention group receiving instruction according to Peyton 's Four-Step Approach ( IG ; n = 17 ) or to a control group receiving st and ard instruction ( CG ; n = 17 ) . Both groups were taught gastric-tube insertion using a manikin . Following each of the two forms of instruction , participants ’ first independent gastric-tube insertions were video recorded and scored by two independent video assessors using binary checklists and global rating forms . The time required for each instructional approach and for the first independent performance of the skill was measured . Results : A total of 34 students agreed to participate in the trial . There were no statistically significant group differences with regard to age , sex , completed education in a medical profession , or completed medical clerkships . The groups did not differ in terms of correct stepwise performance of the procedure as assessed by a binary checklist ( p < .802 ) . However , ratings based on global rating scales assessing professionalism and accompanying patient-doctor communication proved significantly better in IG ( both ps < .001 ) . The length of the different instructional approaches did not differ significantly between the two groups ( IG : 605 ± 65 s ; CG : 572 ± 79 s ; p < .122 ) , but the time needed for the first independent performance of gastric-tube placement on the manikin was significantly shorter in IG ( IG : 168 ± 30 s ; CG : 242 ± 53 s ; p < .001 ) . Conclusions : Peyton 's Four-Step Approach is superior to st and ard instruction with respect to professionalism and accompanying doctor – patient communication and leads to faster performance when trainees perform the learned skill for the first time |
1,631 | 25,140,980 | We also considered other outcomes and at four or more months follow-up we found no effects on drink-driving ( SMD -0.11 ; 95 % CI -0.31 to 0.09 ) , moderate quality of evidence ; or other alcohol-related risky behaviour ( SMD -0.14 ; 95 % CI -0.30 to 0.02 ) , moderate quality of evidence .Further analyses showed that the type of control comparison ( assessment only versus alternative intervention ) did not predict the outcome in a clear or straightforward way ; and there was no consistent relationship between the duration of the MI intervention ( in minutes ) and effect size .
The results of this review indicate that there are no substantive , meaningful benefits of MI interventions for the prevention of alcohol misuse . | BACKGROUND Globally , harmful use of alcohol results in approximately 2.5 million deaths each year .
About 9 % of these deaths are young people between the ages of 15 and 29 years ( WHO 2011 ) , mainly result ing from motor vehicle accidents , homicides , suicides and drownings .
Hazardous drinking levels for men ( consuming over 40 g/day alcohol on average , that is 5 units ) double the risk of liver disease , raised blood pressure , some cancers and violent death ( because some people who have this average alcohol consumption drink heavily on some days ) .
For women , over 24 g/day average alcohol consumption ( 3 units ) increases the risk for developing liver disease and breast cancer .
Motivational interviewing ( MI ) is a popular technique for addressing excessive drinking in young adults but its effectiveness has not previously been examined in a Cochrane review .
OBJECTIVES The specific objectives were:(1 ) to summarise current evidence about the effects of MI intended to address alcohol and alcohol-related problems in young adults , compared with no intervention or a different intervention , on alcohol consumption and other substantive outcome measures ; ( 2 ) to investigate whether the effects of MI are modified by the length of the intervention . | OBJECTIVE This study examined the effectiveness of three peer-facilitated brief alcohol interventions -small group motivational interviewing , motivationally enhanced peer theater , and an interactive alcohol-education program-with students engaging in high-risk drinking who were referred for alcohol policy violations . METHOD Undergraduate students referred for alcohol policy violations ( N = 695 ) at a large northeastern public university were r and omized to one of the three conditions . Six-month follow-up data were collected on drinking frequency and quantity , negative consequences , use of protective behaviors , and perceptions of peers ' drinking norms . RESULTS There were no statistically significant overall pre-post effects or treatment effects . However , exploratory analyses indicated that decreases in perceived norms and increases in use of protective behavioral strategies were associated with reductions in alcohol use and alcohol-related problems at follow-up ( p < .01 ) . CONCLUSIONS The presence of nonsignificant pre-post or main effects is , in part , consistent with recent research indicating that sanctioned college students may immediately reduce drinking in response to citation and that brief interventions may not contribute to additional behavioral change . The presence of statistically significant correlations between alcohol use and related problems with corrections in norms misperceptions and increased use of protective behaviors at the individual level holds promise for both research and practice . The integration of elements addressing social norms and use of protective behaviors within brief cognitive-behavioral intervention protocol s delivered by trained peer facilitators warrants further study using r and omized clinical trials AIM To establish the efficacy of a brief motivational intervention compared to feedback only when delivered in an emergency department for reducing alcohol use and problems among young adults . DESIGN Two-group r and omized controlled trial with follow-up assessment s at 6 and 12 months . SETTING Level I Trauma Center . PARTICIPANTS A total of 198 18 - 24-year-old patients who were either alcohol positive upon hospital admission or met screening criteria for alcohol problems . INTERVENTION Participants were assigned r and omly to receive a one-session motivational intervention ( MI ) that included personalized feedback , or the personalized feedback report only ( FO ) . All participants received additional telephone contact 1 month and 3 months after baseline . MEASUREMENTS Demographic information , alcohol use , alcohol problems and treatment seeking . FINDINGS Six months after the intervention MI participants drank on fewer days , had fewer heavy drinking days and drank fewer drinks per week in the past month than did FO patients . These effects were maintained at 12 months . Clinical significance evaluation indicated that twice as many MI participants as FO participants reliably reduced their volume of alcohol consumption from baseline to 12 months . Reductions in alcohol-related injuries and moving violations , and increases in alcohol treatment-seeking were observed across both conditions at both follow-ups with no differences between conditions . CONCLUSIONS This study provides new data supporting the potential of the motivational intervention tested to reduce alcohol consumption among high-risk youth AIMS This study aim ed at testing the effectiveness of a brief motivational intervention ( BI ) compared with a minimal intervention ( MI ) for reducing alcohol consumption in adult , alcohol-positive traffic casualties . METHODS Patients were recruited at the emergency room of a trauma hospital and screened for alcohol by a qualitative saliva test ( positive from a blood alcohol concentration of 0.02 g/l ) . Positive patients ( 13.3 % ) who accepted entering the study were r and omly allocated into BI and MI . Baseline assessment was the same for all patients . Blind telephone follow-ups were performed at months 3 , 6 , and 12 , and results were analysed by protocol and by intention-to-treat analysis . RESULTS After 1 year of follow-up , 67 % of the patients had reduced their consumption , the percentage of heavy drinkers had dropped by 47 % , and 62 % of baseline AUDIT-C positive patients ( hazardous drinkers ) had become negative . Binge drinking dropped significantly ( P < 0.05 ) . Results at month 12 were in line with the previous ones . CONCLUSIONS The effectiveness of BI compared with MI has not been verified , but a significant reduction in consumption has been observed in the whole sample , without significant differences by type of intervention . The persistence and dimension of changes suggest a real effect of both interventions , although the lack of a pure control group does not allow definitive conclusions . Traffic casualties are in a teachable moments to benefit from easy and cheap interventions This study tested the efficacy of behavioral treatments for alcohol use disorders ( AUD ) among men who have sex with men ( MSM ) and who are at risk for HIV transmission . HIV-negative MSM with current AUD ( N = 198 ) were recruited , offered treatment focused on reducing drinking and HIV risk , and followed during treatment and 12 months posttreatment . Participants ( n = 89 ) accepted treatment and were r and omized to either 4 sessions of motivational interviewing ( MI ) or 12 sessions of combined MI and coping skills training ( MI + CBT ) . Other participants ( n = 109 ) declined treatment but were followed , forming a non-help-seeking group ( NHS ) . MI yielded significantly better drinking outcomes during the 12-week treatment period than MI + CBT , but posttreatment outcomes were equivalent . NHS participants significantly reduced their drinking as well . Service delivery and treatment research implication s are discussed OBJECTIVES Adolescents in their late teens and early 20s have the highest alcohol consumption in the United States ; binge drinking peaks at age 21 - 25 years . Underage drinking is associated with many negative consequences , including academic problems and risk of intentional and unintentional injuries . This study tested the effectiveness of pediatric emergency department ( PED ) screening and brief intervention to reduce alcohol consumption and associated risks . METHODS A three-group r and omized assignment trial was structured to test differences between intervention ( I ) and st and ard assessed control ( AC ) groups in alcohol consumption and alcohol-related behaviors from baseline to 12 months and to compare the AC group with a minimally assessed control ( MAC ) group to adjust for the effect of assessment reactivity on control group behavior . Patients aged 14 - 21 years were eligible if they screened positive on the Alcohol Use Disorders Identification Test ( AUDIT ) or for binge drinking or high-risk behaviors . The MAC group received a re source h and out , written advice about alcohol-related risks , and a 12-month follow-up appointment . Patients in the AC group were assessed using st and ardized instruments in addition to the MAC protocol . The I group received a peer-conducted motivational intervention , referral to community re sources and treatment if indicated , and a 10-day booster in addition to assessment . Measurements included 30-day self-report of alcohol consumption and alcohol-related behaviors , screens for depression and posttraumatic stress disorder , and self-report of attempts to quit , cut back , or change conditions of use , all repeated at follow-up . Motor vehicle records and medical records were also analyzed for changes from baseline to 1-year follow-up . RESULTS Among 7,807 PED patients screened , 1,202 were eligible ; 853 enrolled ( I , n = 283 ; AC , n = 284 ; MAC , n = 286 ) , with a 12-month follow-up rate of 72 % . At 12 months , more than half of enrollees in Reaching Adolescents for Prevention ( RAP ) attempted to cut back on drinking , and over a third tried to quit . A significantly larger proportion of the I group made efforts to quit drinking and to be careful about situations when drinking compared to AC enrollees , and there was a numerically but not significantly greater likelihood ( p = 0.065 ) among the I group for efforts to cut back on drinking . At 3 months , the likelihood of the I group making attempts to cut back was almost triple that of ACs . For efforts to quit , it was double , and for trying to be careful about situations when drinking , there was a 72 % increase in the odds ratio ( OR ) for the I group . Three-month results for attempts were sustained at 12 months for quit attempts and efforts to be careful . Consumption declined in both groups from baseline to 3 months to 12 months , but there were no significant between-group differences in alcohol-related consequences at 12 months or in alcohol-related risk behaviors . We found a pattern suggestive of assessment reactivity in only one variable at 12 months : the attempt to cut back ( 73.3 % for the I group vs. 64.9 % among the AC group and 54.8 % among the MAC group ) . CONCLUSIONS Brief motivational intervention result ed in significant efforts to change behavior ( quit drinking and be careful about situations while drinking ) but did not alter between-group consumption or consequences By the age of 18 , between 16 and 27 % of adolescents in the U.S. have been arrested for an offense and by the age of 23 this increases to a staggering 25 - 41 % . Most youth that get into legal trouble have a substance abuse problem and many youth report high risk driving behaviors . Adjudication of adolescents for an offense may provide an opportunity to provide a secondary prevention program for such high risk behaviors . In this regard the primary aim of the present study was to test two hypotheses : ( 1 ) that interventions involving group motivational interviewing would decrease future legal charges beyond those achieved by the combination of sanctions and remedial actions otherwise m and ated by the court ; and ( 2 ) that the addition of a trauma room exposure to the group MI intervention would increase the effectiveness of MI in decreasing these future legal charges . Court m and ated youth who have had a high risk driving police charge and /or alcohol related police charge and who are drivers ( n=992 ) were r and omly assigned to one of the three 20h interventions ; enhanced prototypic community service ( CS ) , Motivational Intervention with typical community service ( MI ) , and Motivational Intervention with exposure to a hospital trauma center ( MI-H ) . As hypothesized , the probability of being charged with an offense within the 6 months post-treatment was significantly less for participants in the combined MI groups than those in the CS group . The combined MI groups also had significantly fewer overall number of police charge events than the CS group at 6 months . Mediation analyses revealed that the relationship between MI vs. CS interventions and subsequent police charges was partially accounted for by the youth 's experience of the MI component of the intervention . Despite fewer police charges at 6 months the combined MI group reported ( 1 ) significantly more hazardous drinking and ( 2 ) a greater amount of speeding and distracted driving than the control group over this same 6-month period . Hypothesis 2 , that MI-H would be more effective than MI in reducing police charges , was not supported . This was so despite evidence supporting the hypotheses that ( 1 ) trauma room exposure would increase participants ' emotional arousal during the intervention and ( 2 ) increased arousal would be predictive of fewer police charges . Despite support for the theorized causal pathway , the combination of trauma room exposure and MI did not result in better outcomes than MI combined with traditional community service . Given this discrepancy between empirical supports for the theory in the face of the absence of incremental effectiveness of the MI-H treatment condition , a better underst and ing of the participant 's hospital experience will be necessary if we are to successfully utilize the trauma room exposure to increase the effectiveness of MI interventions for this target group to achieve better outcomes OBJECTIVE To determine whether a brief individual motivational interview ( IMI ) plus a family motivational interview ( Family Check-Up [ FCU ] ) would reduce alcohol use in adolescents treated in an emergency department after an alcohol-related event more effectively than would an IMI only . DESIGN Two-group r and omized design with 3 follow-up time points . SETTING An urban regional level I trauma center . PARTICIPANTS Adolescents aged 13 to 17 years ( N = 125 ) with a positive blood alcohol concentration as tested using blood , breath , or saliva . INTERVENTIONS Either IMI or IMI plus FCU . MAIN OUTCOME MEASURES Drinking frequency ( days per month ) , quantity ( drinks per occasion ) , and frequency of high-volume drinking ( ≥5 drinks per occasion ) . RESULTS Both conditions result ed in a reduction in all drinking outcomes at all follow-up points ( P < .001 for all ) , with the strongest effects at 3 and 6 months . Adding the FCU to the IMI result ed in a somewhat better outcome than did the IMI only on high-volume drinking days at 3-month follow-up ( 14.6 % vs 32.1 % , P = .048 ; odds ratio , 2.76 ; 95 % confidence interval , 0.99 - 7.75 ) . CONCLUSIONS Motivational interventions have a positive effect on drinking outcomes in the short term after an alcohol-related emergency department visit . Adding the FCU to an IMI result ed in somewhat better effects on high-volume drinking at short-term follow-up than did an IMI only . The cost of extra sessions necessary to complete the FCU should be weighed against the potential benefit of reducing high-volume drinking when considering adding the FCU to an IMI for this population OBJECTIVE Motivational interviewing to reduce alcohol and marijuana use among incarcerated adolescents was evaluated . METHOD Adolescents ( N = 162 , 84 % male ; M = 17.10 years old ) were r and omly assigned to receive motivational interviewing or relaxation training , with follow-up assessment 3 months after release . RESULTS Compared with those who received relaxation training , adolescents who received motivational interviewing had lower rates of alcohol and marijuana use at follow-up , with some evidence for moderating effects of depression . At low levels of depression , adolescents who received motivational interviewing had lower rates of use . Adolescents who received relaxation training and who had high levels of depressive symptoms early in incarceration showed less use at follow-up than those low in depressive symptoms who received relaxation training . CONCLUSIONS This brief motivational interviewing intervention during incarceration reduces alcohol and marijuana use after release . In addition , depressive symptoms early in incarceration should be considered in treating these adolescents , but more work is needed to extend follow-up period and account for the impact of depression on outcomes Motivational interviewing ( MI ) is a brief intervention that has been shown to reduce heavy drinking among college students . Because all college studies of MI to date have included a personalized feedback report , it remains unclear which of the components is necessary to produce behavior change . This study evaluated the separate and collective effects of MI and feedback among 122 “ binge ” drinking college students . Participants were r and omized to : 1 ) MI with feedback , 2 ) MI without feedback , 3 ) Mailed feedback only , 4 ) MI with mailed feedback , or 5 ) Assessment only control . At an eight-week follow-up , all groups reduced their consumption , peak BAC , consequences , and dependence symptoms . For females , there were reductions in consequences and dependence symptoms in groups that received feedback , as compared to groups that did not receive feedback . For females , there was an effect of the feedback on consequences and dependence symptoms , but was no overall effect of MI on any outcome measure BACKGROUND AND OBJECTIVES : Emergency department ( ED ) visits present an opportunity to deliver brief interventions ( BIs ) to reduce violence and alcohol misuse among urban adolescents at risk for future injury . Previous analyses demonstrated that a BI result ed in reductions in violence and alcohol consequences up to 6 months . This article describes findings examining the efficacy of BIs on peer violence and alcohol misuse at 12 months . METHODS : Patients ( 14–18 years of age ) at an ED reporting past year alcohol use and aggression were enrolled in the r and omized control trial , which included computerized assessment , r and om assignment to control group or BI delivered by a computer or therapist assisted by a computer . The main outcome measures ( at baseline and 12 months ) included violence ( peer aggression , peer victimization , violence-related consequences ) and alcohol ( alcohol misuse , binge drinking , alcohol-related consequences ) . RESULTS : A total of 3338 adolescents were screened ( 88 % participation ) . Of those , 726 screened positive for violence and alcohol use and were r and omly selected ; 84 % completed 12-month follow-up . In comparison with the control group , the therapist assisted by a computer group showed significant reductions in peer aggression ( P < .01 ) and peer victimization ( P < .05 ) at 12 months . BI and control groups did not differ on alcohol-related variables at 12 months . CONCLUSIONS : Evaluation of the SafERteens intervention 1 year after an ED visit provides support for the efficacy of computer-assisted therapist brief intervention for reducing peer violence This study evaluated the efficacy of two brief personalized feedback interventions ( PFIs ) using identical feedback and motivational interviewing strategies aim ed at reducing alcohol consumption and alcohol-related problems to two control conditions among a sample of high-risk drinking college students . Students ( N = 152 ) were r and omly assigned to a computer-delivered PFI with a video interviewer , a face-to-face PFI with a live interviewer , a comprehensive assessment condition , or a minimal assessment -only condition . At 10 weeks posttreatment , the face-to-face PFI significantly reduced weekly drinking quantity and peak and typical blood alcohol concentration compared with the comprehensive assessment and minimal assessment -only conditions ( d values ranged from 0.32 to 0.61 ) . No significant between-group differences were evidence d for the computer-delivered PFI condition , although effect sizes were comparable to other college drinking studies using computer-delivered interventions ( d values ranged from 0.20 to 0.27 ) . Results provide further support for the use of a face-to-face PFI to help reduce college students ' alcohol consumption and suggest that a video interviewer in the context of a computer-delivered PFI is likely a helpful but not necessarily a complete substitute for a live interviewer Motivational interviewing ( MI ) is an effective treatment for substance use disorders ( SUDs ) that focuses on resolving ambivalence and increasing commitment to positive behavior change . Although MI has a well-developed clinical theory , research findings have been mixed in supporting its view of how change occurs . The primary aim of this pilot study was to test hypothesized MI active ingredients and mechanisms of change in reducing drinking during the initiation of a behavior change episode . Problem drinkers ( N = 89 ) seeking treatment were r and omly assigned to MI , relational MI without directive elements ( spirit-only MI [ SOMI ] ) , or a self-change ( SC ) control condition . Participants were followed during an 8-week treatment period . The first 2 of 4 treatment sessions were videotaped and coded for fidelity , discriminability , and change talk . Overall , conditions demonstrated high fidelity . As predicted , change talk significantly increased in MI relative to the SOMI condition . Drinking was significantly reduced at end treatment , but the reduction was equivalent across conditions . Post hoc analyses found that MI reduced drinking more rapidly than SOMI and SC and that increased change talk mediated the effects of MI relative to SOMI during the week immediately following the first session . Findings are discussed in the context of the pilot nature of the study and the relative absence of experimental tests of mechanisms of behavior change in SUD treatment research to test early nutritional interventions and prospect i ve observational cohorts . RCTs are generally accepted as method ologically the best approach for informing health policy . They can equalise unknown as well as known confounding factors and so can demonstrate causation ; they permit estimation of effect size and so can be used to assess likely OBJECTIVE The current study examined the efficacy of mailed personalized normative feedback ( PNF ) as a brief alcohol intervention for at-risk college drinkers , and investigated discrepancy as a possible mediator of the intervention effect . METHOD Participants consisted of 100 at-risk college drinkers who completed an alcohol-use assessment at baseline , 6-week posttest and 6-month follow-up . Measures included number of drinks consumed per heaviest drinking week , frequency of heavy-drinking episodes , peak blood alcohol concentration and number of alcohol-related problems , all for the last month . Participants were r and omly assigned to either a mailed brief intervention ( MBI ; n = 49 ) or attention-control ( C ; n = 51 ) group . The MBI group received mailed PNF that was based on baseline responses to the drinking measures ; the C group received a psychoeducational brochure about alcohol . RESULTS Mixed-model , repeated measures ANOVAs were used to examine the effects of time , group and gender on discrepancy and the drinking variables . Following the intervention , the MBI group reported significantly higher perceived discrepancy between self and others ' drinking than the C group . The MBI group reported consuming significantly fewer drinks per heaviest drinking week and engaging in heavy episodic drinking less frequently than the C group at the 6-week posttest ; however , these differences were no longer evident at the 6-month follow-up . Hierarchical regression analyses did not provide evidence for the hypothesized mediating effect of discrepancy . CONCLUSIONS Mailed PNF may be a cost- and time-efficient means of developing discrepancy and temporarily reducing heavy alcohol consumption among at-risk college drinkers BACKGROUND The prevention of initiation of tobacco , alcohol and drug use is a major societal challenge , for which the existing research literature is generally disappointing . This study aim ed to test the effectiveness of adaptation of Motivational Interviewing ( MI ) for universal prevention purpose s , i.e. to prevent initiation of new substance use among non-users , and to reduce risks among existing users . METHODS Cluster r and omised trial with 416 students aged 16 - 19 years old recruited in 12 London Further Education colleges without regard to substance use status . Individualised MI was compared with st and ard practice classroom-delivered Drug Awareness intervention , both delivered over the course of one lesson . Prevalence , initiation and cessation rates for the 3 target behaviours of cigarette smoking , alcohol consumption and cannabis use , along with reductions in use and harm indicators after both 3 and 12 months were assessed . RESULTS This adaptation of MI was not demonstrated to be effective in either intention-to-treat or sub-group analyses for any outcome . Unexpected lower levels of cannabis initiation and prevalence were found in the Drug Awareness control condition . CONCLUSIONS This particular adaptation of MI is ineffective as a universal drug prevention intervention and does not merit further study Many college women are at risk for pregnancy , and binge drinking college women are often at risk for alcohol-exposed pregnancy . Brief interventions with sustainable outcomes are needed , particularly for college women who are binge drinking , at risk for pregnancy , and at increased risk of alcohol-exposed pregnancy . Two-hundred-twenty-eight women at a Mid-Atlantic urban university at risk for alcohol-exposed pregnancy enrolled in the r and omized clinical trial , and 207 completed the 4 month follow-up . The BALANCE intervention used Motivational Interviewing plus feedback to target drinking and contraception behaviors . Main outcome measures included ( 1 ) the rate of risk for alcohol-exposed pregnancy , ( 2 ) the rate of risk drinking , and ( 3 ) the rate of pregnancy risk . At 4-month follow-up , the rate of alcohol-exposed pregnancy risk was significantly lower in the intervention ( 20.2 % ) than the control condition ( 34.9 % ) , ( P < .02 ) . Assignment to the intervention condition halved the odds of women remaining at risk for alcohol-exposed pregnancy , while not receiving the intervention doubled the odds of continued alcohol-exposed pregnancy risk ( OR = 2.18 ; 95 % CI = 1.16–4.09 ) . A baseline history of blackouts , continued high blood alcohol drinking days at 1 month , and continued risk for pregnancy at 1 month independently contributed to a multivariate model of continued alcohol-exposed pregnancy risk at 4 month follow-up . BALANCE reduced alcohol-exposed pregnancy risk , with similar outcomes to longer interventions . Because early response predicted sustained alcohol-exposed pregnancy risk reduction , those who fail to achieve initial change could be identified for further intervention . The BALANCE intervention could be adopted into existing student health or university alcohol programs . The risks of unintended pregnancy and alcohol-exposed pregnancy among binge drinking women in college merit greater prevention efforts BACKGROUND Heavy drinking is one of the leading causes of morbidity and mortality in young men . Brief motivational intervention ( BMI ) has shown promising results for young people , but has never been tested in young men in the community who volunteered to receive an intervention . METHODS We evaluated the effectiveness of BMI in reducing alcohol use among heavy episodic users and in maintaining low-risk drinking among nonheavy episodic users . Participants were French-speaking young men attending the m and atory Swiss army conscription process . They were offered the opportunity to receive a 20-minute BMI , and those interested were r and omized into an intervention group ( BMI immediately ) or into a control group ( BMI after the 6-month follow-up assessment , in a waiting list design ) . Analyses were conducted separately for heavy and nonheavy episodic users ( separated using baseline heavy episodic use frequency ) as the hypotheses tested were different between both groups ( primary vs. secondary prevention intervention ) . RESULTS From a pool of 6,085 young men invited to receive BMI , 727 ( 11.9 % ) showed up and 572 were included in the study ( after exclusions related to organizational aspects of the conscription process ) . Among nonheavy episodic users , there was a protective effect of BMI on weekly alcohol use ( p < 0.05 ) . Among heavy episodic users , there were no significant effects of BMI . CONCLUSIONS About 12 % of young men were interested in addressing their drinking within the BMI framework , suggesting that there is some need for easily accessible alcohol intervention . The present intervention did have a preventive effect among low-risk young drinkers in helping them maintain their patterns of alcohol use . An explanation for the lack of effectiveness among heavy episodic users might be that those individuals interested in BMI had patterns of more severe alcohol use , thereby making change more difficult OBJECTIVE This study evaluated the costs and cost-effectiveness of combining motivational interviewing with feedback to address heavy drinking among university freshmen . METHOD Microcosting methods were used in a prospect i ve cost and cost-effectiveness study of a r and omized trial of assessment only ( AO ) , motivational interviewing ( MI ) , feedback only ( FB ) , and motivational interviewing with feedback ( MIFB ) at a large public university in the southeastern United States . Students were recruited and screened into the study during freshman classes based on recent heavy drinking . A total of 727 students ( 60 % female ) were r and omized , and 656 had sufficient data at 3-months ' follow-up to be included in the cost-effectiveness analysis . Effectiveness outcomes were changes in average drinks per drinking occasion and number of heavy drinking occasions . RESULTS Mean intervention costs per student were $ 16.51 for MI , $ 17.33 for FB , and $ 36.03 for MIFB . Cost-effectiveness analysis showed two cost-effective interventions for both outcomes : AO ( $ 0 per student ) and MIFB ( $ 36 per student ) . CONCLUSIONS This is the first prospect i ve cost-effectiveness study to our knowledge to examine MI for heavy drinking among students in a university setting . Despite being the most expensive intervention , MIFB was the most effective intervention and may be a cost-effective intervention , depending on a university 's willingness to pay for changes in the considered outcomes This study examined the effectiveness of a single-session group motivational enhancement alcohol intervention on adjudicated male college students . Over two sequential academic years , 230 students sanctioned by the university for alcohol-related infractions attended a 60- to 75-minute group intervention . The intervention consisted of a timeline followback , social norms education , decisional balance for behavioral change , blood alcohol content ( BAC ) information , expectancy challenge , and generation of behavioral goals . Participants were followed weekly for three months and showed reductions in drinking ( 29 % ) and alcohol-related consequences ( 32 % ) at three-month follow-up . The intervention was successful in reducing drinking for both first-year students and upperclassmen , with reductions appearing to be a function of the intervention and not the citation itself . Furthermore , a post hoc control condition revealed that those participants r and omly assigned to the intervention group condition reduced drinking ( 19 % ) and alcohol-related consequences ( 44 % ) more than participants in the control condition over one month . These results provide continued evidence of the effectiveness of group motivational enhancement interventions with adjudicated male college students OBJECTIVE This study tested the effectiveness of brief primary care provider interventions delivered in a college student health center to a sample of college students who screened positive for high-risk drinking . METHOD Between November 2005 and August 2006 , 8,753 students who presented as new patients to the health service at a large public university were screened for high-risk drinking , and 2,484 students ( 28 % ) screened positive on the 5/4 gender-specific high-risk drinking question ( i.e. , five or more drinks per occasion for men and four or more for women ) . Students who screened positive for high-risk drinking and consented to participate ( N= 363 ; 52 % female ) were r and omly assigned either to a control group ( n = 182 ) or to an experimental group ( n = 181 ) . Participants in the experimental group received two brief intervention sessions that were founded in motivational interviewing techniques and delivered by four specially trained providers within the student health center . Data on alcohol use and related harms were obtained from a Web-based Healthy Lifestyle Question naire , 30-day Timeline Followback alcohol-use diaries , the Rutgers Alcohol Problem Index ( RAPI ) , and eight items from the Drinker Inventory of Consequences-2L . RESULTS Repeated measures analysis showed that , compared with the control group ( C ) , the intervention group ( I ) had significant reductions in typical estimated blood alcohol concentration ( BAC ) ( C = .071 vs I = .057 at 3 months ; C = .073 vs I = .057 at 6 months ) , peak BAC ( C = . 142 vs I = .112 at 3 months ; C = .145 vs I = .108 at 6 months ) , peak number of drinks per sitting ( C = 8.03 vs I = 6.87 at 3 months ; C = 7.98 vs I = 6.52 at 6 months ) , average number of drinks per week ( C = 9.47 vs I = 7.33 at 3 months ; C = 8.90 vs I = 6.16 at 6 months ) , number of drunk episodes in a typical week ( C = 1.24 vs I = 0.85 at 3 months ; C = 1.10 vs I = 0.71 at 6 months ) , number of times taken foolish risks ( C = 2.24 vs I = 1.12 at 3 months ) , and RAPI sum scores ( C = 6.55 vs I = 4.96 at 6 months ; C = 6.17 vs I = 4.58 at 9 months ) . CONCLUSIONS Brief interventions delivered by primary care providers in a student health center to high-risk-drinking students may result in significantly decreased alcohol consumption , high-risk drinking , and alcohol-related harms OBJECTIVE To examine the maintenance of effects of Motivational Enhancement Therapy ( MET ) shown to improve risk behaviors and viral load in youth living with HIV ( YLH ) immediately posttreatment . METHODS Sixty-five youth ( ages 16 - 25 years ) were r and omized to Healthy Choices or a waitlist control . Frequency of substance use , frequency of unprotected intercourse , and viral load were obtained at baseline , 3 , and 6 months after study entry . The waitlist control then received intervention . An additional data collection was obtained at 9 months for follow-up of the original treatment group . RESULTS One-tailed ANOVA showed that the treatment group had greater reductions in viral load and alcohol use from baseline to 6 months . These reductions appeared to be maintained at 9-month follow-up . Improvements in sexual risk were not evident . CONCLUSIONS MET showed significant promise in reducing substance use and in improving HIV-related health in YLH immediately posttreatment . These effects were maintained after treatment termination Alcohol consumption among college students has become an increasing problem that requires attention from college administrators , staff , and research ers . Despite the physiological differences between men and women , college women are drinking at increasingly risky rates , placing them at increased risk for negative consequences . The current study tested a group motivational enhancement approach to the prevention of heavy drinking among 1st-year college women . Using a r and omized design , the authors assigned participants either to a group that received a single-session motivational enhancement intervention to reduce risky drinking that focused partly on women 's specific reasons for drinking ( n = 126 ) or to an assessment -only control group ( n = 94 ) . Results indicated that , relative to the control group participants , intervention participants drank fewer drinks per week , drank fewer drinks at peak consumption events , and had fewer alcohol-related consequences over a 10-week follow-up . Further , the intervention , which targeted women 's reasons for drinking , was more effective in reducing consumption for participants with high social and enhancement motivations for drinking The authors evaluated the efficacy of Brief Alcohol Screening and Intervention for College Students ( BASICS - L. A. Dimeff , J. S. Baer , D. R. Kivlahan , & G. A. Marlatt , 1999 ) , a single session of drinking-related feedback intended to reduce heavy drinking and related harm . College student drinkers ( N = 99 ) were assigned to BASICS , an educational intervention , or an assessment -only control group . At 3 months postintervention . there were no overall significant group differences , but heavier drinking BASICS participants showed greater reductions in weekly alcohol consumption and binge drinking than did heavier drinking control and education participants . At 9 months , heavier drinking BASICS participants again showed the largest effect sizes . BASICS participants evaluated the intervention more favorably than did education participants . This study suggests that BASICS may be more efficacious than educational interventions for heavier drinking college students Criminally involved adolescents engage in high levels of risky sexual behavior and alcohol use , and alcohol use may contribute to lack of condom use . Detained adolescents ( n = 484 ) were r and omized to ( 1 ) a theory-based sexual risk reduction intervention ( GPI ) , ( 2 ) the GPI condition with a group-based alcohol risk reduction motivational enhancement therapy component ( GPI + GMET ) , or ( 3 ) an information-only control ( INFO ) . All interventions were presented in same-sex groups in single sessions lasting from 2 to 4 hr . Changes to putative theoretical mediators ( attitudes , perceived norms , self-efficacy , and intentions ) were measured immediately following intervention administration . The primary outcomes were risky sexual behavior and sexual behavior while drinking measured 3 months later ( 65.1 % retention ) . The GPI + GMET intervention demonstrated superiority over both other conditions in influencing theoretical mediators and over the INFO control in reducing risky sexual behavior . Self-efficacy and intentions were significant mediators between condition and later risky sexual behavior . This study contributes to an underst and ing of harm reduction among high-risk adolescents and has implication s for underst and ing circumstances in which the inclusion of GMET components may be effective OBJECTIVES This paper presents up to 5 years post-program outcomes of Project Towards No Drug Abuse ( Project TND ) , a drug abuse prevention program conducted in South California alternative high school system during years 1994 - 1999 . METHODS The effects of a 9-session health motivation -- social skills -- decision-making curriculum were evaluated . Twenty-one schools recruited were r and omly assigned to st and ard care ( control ) , classroom only , or a classroom plus semester-long school-as-community component . Last 30-day use of cigarettes , alcohol , marijuana , and hard drugs were assessed at three time intervals : short-term ( year 1 ) , middle-term ( years 2 or 3 ) , and long-term ( years 4 or 5 ) . Multilevel r and om coefficients modeling were employed to estimate the adjusted levels of substance use . RESULTS Among 1578 baseline subjects , follow-up data were available for 68 % ( year 1 ) , 66 % ( years 2 or 3 ) , and 46 % ( years 4 or 5 ) of subjects , respectively . Results revealed significant positive long-term program effects for hard drug use at year 4 or 5 for the two program interventions ( P = 0.02 ) . CONCLUSIONS Project TND reduced hard drug use in the 46 % who were successfully followed . It is the first program to demonstrate long-term self-reported behavioral effects on hard drug use among high-risk youth by using a school-based , limited-session model OBJECTIVE To evaluate moderators and mediators of brief alcohol interventions conducted in the emergency department . METHODS Patients ( 18 - 24 years ; n = 172 ) in an emergency department received a motivational interview with personalized feedback ( MI ) or feedback only ( FO ) , with 1- and 3-month booster sessions and 6- and 12-month follow-ups . Gender , alcohol status/severity group [ ALC+ only , Alcohol Use Disorders Identification Test ( AUDIT+ ) only , ALC+/AUDIT+ ] , attribution of alcohol in the medical event , aversiveness of the event , perceived seriousness of the event and baseline readiness to change alcohol use were evaluated as moderators of intervention efficacy . Readiness to change also was evaluated as a mediator of intervention efficacy , as were perceived risks/ benefits of alcohol use , self-efficacy and alcohol treatment seeking . RESULTS Alcohol status , attribution and readiness moderated intervention effects such that patients who had not been drinking prior to their medical event , those who had low or medium attribution for alcohol in the event and those who had low or medium readiness to change showed lower alcohol use 12 months after receiving MI compared to FO . In the AUDIT+ only group those who received MI showed lower rates of alcohol-related injury at follow-up than those who received FO . Patients who had been drinking prior to their precipitating event did not show different outcomes in the two interventions , regardless of AUDIT status . Gender did not moderate intervention efficacy and no significant mediation was found . CONCLUSIONS Findings may help practitioners target patients for whom brief interventions will be most effective . More research is needed to underst and how brief interventions transmit their effects OBJECTIVE This study evaluated two brief personal feedback substance-use interventions for students m and ated to the Rutgers University Alcohol and Other Drug Assistance Program for Students ( ADAPS ) : ( 1 ) a brief motivational interview ( BMI ) intervention and ( 2 ) a written feedback-only ( WF ) intervention . A key question addressed by this study was whether there is a need for face-to-face feedback in the context of motivational interviewing to affect changes in substance-use behaviors or whether a written personal feedback profile is enough of an intervention to motivate students to change their substance use . METHOD The sample consisted of 222 students who were m and ated to ADAPS , were eligible for the study , and completed the 3-month follow-up assessment . Eligible students completed a baseline assessment from which a personal feedback profile was created . They were then r and omly assigned to the BMI or WF condition . Students were followed 3 months later . RESULTS Students in both interventions reduced their alcohol consumption , prevalence of cigarette and marijuana use , and problems related to alcohol and drug use between baseline and follow-up . There were no differences between the two intervention conditions in terms of any substance-use outcomes . CONCLUSIONS The results suggest that , under these circumstances and with these students , assessment and WF students changed similarly to those who had an assessment and WF within the context of a BMI . Given the fact that the former is less costly in terms of time and personnel , written profiles may be found to be a cost-effective means of reducing alcohol and drug use and related problems among low- to moderate-risk m and ated college students . More research is needed with m and ated students to determine the efficacy of feedback interventions and to isolate the effects of interventions from the effects of being caught and being reprim and ed to treatment This study tested two forms of alcohol reduction programming for college students . Thirty-seven moderate to heavy drinkers completed measures of quantity/frequency , drinking consequences , and attitude question naires . Participants were r and omly assigned to one of three groups : 1 ) a two-hour information and motivation session plus mailed personal feedback on their drinking ; 2 ) mailed feedback only ; or 3 ) no treatment . At a 6-week follow-up session , the feedback-only group decreased drinks per month as compared to control . No other differences were statistically significant , though decreases favored the treatment conditions about equally over control . Implication s for research and treatment are discussed Healthy Choices is a motivational interviewing intervention targeting multiple risk behaviors among HIV-positive youth . This study investigated the effects of this intervention program specifically on alcohol and marijuana use . Youth living with HIV ( n = 143 , mean age = 20.7 , 51.5 % male ) were recruited from four sites in the United States , and r and omly assigned to intervention or control conditions . The four-session intervention focused on two of three possible problem behaviors based on entry screening ; this study focused on 143 HIV-positive youth who received the intervention for substance use . At 15-month follow-up past-week alcohol use was significantly lower for intervention youth than control youth ( 39.7 % versus 53.6 % , χ2 = 2.81 , 0.05 < p < 0.01 ) ; developmental trajectory analysis demonstrated significant reductions in alcohol use , but more importantly the intervention was effective over time in significantly reducing the adolescent 's probability of being classified into the high-risk trajectory group . The intervention was less effective in reducing marijuana use OBJECTIVE The aim of this study was to evaluate a brief motivational intervention ( BMI ) for reducing risky alcohol use and alcohol-related problems among m and ated ( M ) and voluntary ( V ) student drinkers to determine ( a ) whether BMI -m and ated students report greater decreases in alcohol use and related problems , relative to no treatment ; ( b ) whether a BMI is comparably effective for m and ated and voluntary students ; and ( c ) whether a m and ated control group shows greater changes in alcohol use and related problems relative to a voluntary control group . METHOD Participants were undergraduate student research volunteers ( 62 % male ) who met heavy drinking criteria and completed measures of alcohol use and alcohol problems at baseline and 4 weeks after intervention . Participants ( N = 84 ) were r and omly assigned to treatment ( T ) or assessment -only control ( C ) conditions ( m and ated students were assigned to a brief wait list ) . RESULTS Participants assigned to treatment reported consuming fewer drinks after the intervention ( MT : M = 14.11 drinks ; VT : M = 14.05 ) relative to control groups ( MC : M = 20.71 ; VC : M = 16.53 ) . Evaluation of alcohol-related problems indicated a significant effect of referral status , such that m and ated students reported significantly fewer problems at the follow-up assessment relative to volunteers . CONCLUSIONS BMI s are comparably effective for m and ated and voluntary students and may result in larger reductions in alcohol use than disciplinary attention alone . More longitudinal research is needed to evaluate the long-term impact of a BMI among m and ated students BACKGROUND There is compelling evidence supporting screening and brief intervention ( SBI ) for hazardous drinking , yet it remains underused in primary health care . Electronic ( computer or Web-based ) SBI ( e-SBI ) offers the prospect s of ease and economy of access . We sought to determine whether e-SBI reduces hazardous drinking . METHODS We conducted a r and omized controlled trial in a university primary health care service . Participants were 975 students ( age range , 17 - 29 years ) screened using the Alcohol Use Disorders Identification Test ( AUDIT ) . Of 599 students who scored in the hazardous or harmful range , 576 ( 300 of whom were women ) consented to the trial and were r and omized to receive an information pamphlet ( control group ) , a Web-based motivational intervention ( single-dose e-SBI group ) , or a Web-based motivational intervention with further interventions 1 and 6 months later ( multidose e-SBI group ) . RESULTS Relative to the control group , the single-dose e-SBI group at 6 months reported a lower frequency of drinking ( rate ratio [ RR ] , 0.79 ; 95 % confidence interval [ CI ] , 0.68 - 0.94 ) , less total consumption ( RR , 0.77 ; 95 % CI , 0.63 - 0.95 ) , and fewer academic problems ( RR , 0.76 ; 95 % CI , 0.64 - 0.91 ) . At 12 months , statistically significant differences in total consumption ( RR , 0.77 ; 95 % CI , 0.63 - 0.95 [ equivalent to 3.5 st and ard drinks per week ] ) and in academic problems ( RR , 0.80 ; 95 % CI , 0.66 - 0.97 ) remained , and the AUDIT scores were 2.17 ( 95 % CI , -1.10 to -3.24 ) points lower . Relative to the control group , the multidose e-SBI group at 6 months reported a lower frequency of drinking ( RR , 0.85 ; 95 % CI , 0.73 - 0.98 ) , less total consumption ( RR , 0.79 ; 95 % CI , 0.64 - 0.97 [ equivalent to 3.0 st and ard drinks per week ] ) , reduced episodic heavy drinking ( RR , 0.65 ; 95 % CI , 0.45 - 0.93 ) , and fewer academic problems ( RR , 0.78 ; 95 % CI , 0.65 - 0.93 ) . At 12 months , statistically significant differences in academic problems remained ( RR , 0.75 ; 95 % CI , 0.62 - 0.90 ) , while the AUDIT scores were 2.02 ( 95 % CI , -0.97 to -3.10 ) points lower . CONCLUSIONS Single-dose e-SBI reduces hazardous drinking , and the effect lasts 12 months . Additional sessions seem not to enhance the effect . Trial Registration www.anzctr.org.au Identifier : ACTRN012607000103460 BACKGROUND University students drink more heavily than their nonstudent peers and are often unaware that their drinking is risky and exceeds normative levels . We tested the efficacy of a proactive Web-based alcohol screening and brief intervention program . METHODS A r and omized controlled trial was conducted at an Australian university in 2007 . Invitations were sent to 13 000 undergraduates ( age range , 17 - 24 years ) to complete a Web-based Alcohol Use Disorders Identification Test . Of 7237 students who responded , 2435 scored in the hazardous/harmful range ( > or = 8) and were r and omized , and 2050 ( 84 % ) completed at least 1 follow-up assessment . Intervention was 10 minutes of Web-based motivational assessment and personalized feedback . Controls received only screening . Follow-up assessment s were conducted at 1 and 6 months with observers and participants blinded to allocation . Outcome measures were drinking frequency , typical occasion quantity , overall volume , number of personal problems , an academic problems score , prevalence of binge drinking , and prevalence of heavy drinking . RESULTS Mean ( SD ) baseline Alcohol Use Disorders Identification Test scores for control and intervention groups were 14.3 ( 5.1 ) and 14.2 ( 5.1 ) , respectively . After 1 month , participants receiving intervention drank less often ( rate ratio [ RR ] , 0.89 ; 95 % confidence interval [ CI ] , 0.83 - 0.94 ) , smaller quantities per occasion ( RR , 0.93 ; 95 % CI , 0.88 - 0.98 ) , and less alcohol overall ( RR , 0.83 ; 95 % CI , 0.78 - 0.90 ) than did controls . Differences in alcohol-related harms were nonsignificant . At 6 months , intervention effects persisted for drinking frequency ( RR , 0.91 ; 95 % CI , 0.85 - 0.97 ) and overall volume ( RR , 0.89 ; 95 % CI , 0.82 - 0.96 ) but not for other variables . CONCLUSION Proactive Web-based screening and intervention reduces drinking in undergraduates , and such a program could be implemented widely OBJECTIVE To evaluate the effectiveness of brief motivational interviewing and an educational brochure when delivered in emergency room to reduce alcohol abuse and related problems among adolescents and young adults . METHOD A r and omized single-blind clinical trial with a three-month follow-up was carried out at three emergency rooms from October 2004 to November 2005 ; subjects assessed were 16 - 25 years old treated for alcohol related events up to 6 hours after consumption . Socio-demographic data , quantity , frequency and negative consequences of alcohol consumption , motivation to change habits and future risk perception were evaluated . Statistical analysis was performed on subjects who completed follow-up ( completers ) . ANCOVA model was used to analyze the difference between the intervention groups with statistical significance level α = 5 % and confidence interval ( CI ) of 95 % . RESULTS 186 subjects formed the initial sample , being 175 included and r and omized to the educational brochure group ( n = 88 ) or motivational interviewing group ( n = 87 ) . Follow-up assessment was performed in 85.2 % of the sample . No significant difference between groups was observed . However , significant reductions ( p < 0.01 ) in related problems and alcohol abuse were found in both groups . CONCLUSION In this sample a reduction of alcohol use and related problems was observed . Preliminary data indicate that controlled clinical trials with motivational interviewing , educational brochure and nonintervention should be of future interest among Brazilian adolescent population To investigate the impact of counselor style , a 2-session motivational checkup was offered to 42 problem drinkers ( 18 women and 24 men ) who were r and omly assigned to 3 groups : ( a ) immediate checkup with directive-confrontational counseling , ( b ) immediate checkup with client-centered counseling , or ( c ) delayed checkup ( waiting-list control ) . Overall , the intervention result ed in a 57 % reduction in drinking within 6 weeks , which was maintained at 1 year . Clients receiving immediate checkup showed significant reduction in drinking relative to controls . The 2 counseling styles were discriminable on therapist behaviors coded from audiotapes . The directive-confrontational style yielded significantly more resistance from clients , which in turn predicted poorer outcomes at 1 year . Therapist styles did not differ in overall impact on drinking , but a single therapist behavior was predictive ( r = .65 ) of 1-year outcome such that the more the therapist confronted , the more the client drank OBJECTIVE St and ardized measures of self-reported alcohol use are the predominant method by which change in alcohol use following interventions is evaluated . This study examined whether the invariance of the test-retest pretreatment Alcohol Use Disorders Identification Test ( AUDIT ) was affected by the treatment experience . In this study , the intervening exposure was to motivational interviewing ( MI ) versus community service ( CS ) , the treatment-as-usual control group . METHOD Analyses were conducted on a sub sample of court-referred 16- to 21-year-olds recruited into a r and omized controlled trial examining the effects of MI on alcohol use and police charges for risky driving and /or drinking . Youths were r and omized to CS or MI . A sub sample of 478 participants , who at baseline completed the AUDIT in reference to alcohol use for the 6 months before their conviction , later repeated the AUDIT at treatment completion , in reference to the same 6-month baseline period . RESULTS At completion of treatment , participants receiving CS had a significant decrease in baseline AUDIT scores , whereas those in MI reported no significant change . The difference between the two groups was significant ( p = .02 ) . Also , of those who reported no drinking before treatment , after receiving MI , 33.5 % changed their response and acknowledged pretreatment drinking , compared with only 8.3 % in CS . CONCLUSIONS These results suggest that treatment received may differentially affect a st and ardized measure of self-reported risky drinking . This effect may be attributable to the treatment experience and /or the experience of the control group . Possible explanations for the effect are explored , including more honesty because of a trusting therapeutic alliance and a response shift bias . Differential change in self-report might affect treatment outcome assessment . Depending on the treatment contrasts , research that relies on pre- to post-treatment changes in self-report may be underestimating treatment effects The aim of this study was to identify whether a brief motivational interviewing and cognitive-behavioural-based alcohol intervention group ( AIG ) programme is feasible with young people at risk of developing a problem with alcohol , and to assess the short-term effectiveness of the intervention . Participants were assigned r and omly to receive a group intervention of four sessions duration ( n=17 ; AIG ) or no treatment ( n=17 , control group ) . Participants were volunteers recruited from a youth centre on the Central Coast of New South Wales , Australia , comprising youths aged 12 - 19 years who were interested in participating in the study . The Readiness to Change Question naire , items from the AUDIT , the DAP Quick Screen and a knowledge question naire were administered at pretreatment , post-treatment and at 1- and 2-month follow-ups . Participants in the AIG programme showed an increase in readiness to reduce their alcohol consumption . They also reduced their frequency of drinking at post-treatment and the first follow-up assessment , while the control group reported increases at the second follow-up assessment . The control group also increased their hazardous drinking and frequency of binge drinking compared to the AIG . The intervention appeared to improve the AIG participants ' knowledge about alcohol and its effects . The results provide preliminary evidence for the effectiveness of the AIG programme in training young people to set limits on alcohol consumption , increase awareness of safe drinking levels and the effects of alcohol abuse . This pilot study also showed that young people who are identified as being ' at risk ' of developing alcohol abuse , and who are also ambivalent about changing drinking behaviours , can be recruited and retained in a treatment programme Motivational interviewing ( MI ) is a counseling style that has been shown to reduce heavy drinking among college students . To date , all studies of MI among college students have used a format that includes a feedback profile delivered in an MI style . This study was a dismantling trial of MI and feedback among heavy-drinking college students . After an initial screen , 279 heavy-drinking students were r and omized to ( a ) Web feedback only , ( b ) a single MI session without feedback , ( c ) a single MI session with feedback , or ( d ) assessment only . At 6 months , MI with feedback significantly reduced drinking , as compared with assessment only ( effect size = .54 ) , MI without feedback ( effect size = .63 ) , and feedback alone ( effect size = .48 ) . Neither MI alone nor feedback alone differed from assessment only . Neither sex , race or ethnicity , nor baseline severity of drinking moderated the effect of the intervention . Norm perceptions mediated the effect of the intervention on drinking . MI with feedback appears to be a robust intervention for reducing drinking and may be mediated by changes in normative perceptions This r and omized controlled trial evaluated the efficacy of a brief intervention design ed to reduce the harmful consequences of heavy drinking among high-risk college students . Students screened for risk while in their senior year of high school ( 188 women and 160 men ) were r and omly assigned to receive an individualized motivational brief intervention in their freshman year of college or to a no-treatment control condition . A normative group selected from the entire screening pool provided a natural history comparison . Follow-up assessment s over a 2-year period showed significant reductions in both drinking rates and harmful consequences , favoring students receiving the intervention . Although high-risk students continued to experience more alcohol problems than the natural history comparison group over the 2-year period , most showed a decline in problems over time , suggesting a developmental maturational effect AIM To test whether a single session of motivational interviewing ( discussing alcohol , tobacco and illicit drug use ) would lead successfully to reduction in use of these drugs or in perceptions of drug-related risk and harm among young people . DESIGN Cluster r and omized trial , allocating 200 young people in the natural groups in which they were recruited to either motivational interviewing ( n=105 ) or non-intervention education-as-usual control condition ( n=95 ) . SETTING Ten further education colleges across inner London . PARTICIPANTS Two hundred young people ( age range 16 - 20 years ) currently using illegal drugs , with whom contact was established through peers trained for the project . INTERVENTION The intervention was adapted from the literature on motivational interviewing in the form of a 1-hour single-session face-to-face interview structured by a series of topics . MEASUREMENTS Changes in self-reported cigarette , alcohol , cannabis and other drug use and in a range of drug-specific perceptions and other indicators of risk and harm . Measurement at recruitment and follow-up interview 3 months later . FINDINGS A good follow-up rate ( 89.5 % ; 179 of 200 ) was achieved . In comparison to the control group , those r and omized to motivational interviewing reduced their of use of cigarettes , alcohol and cannabis , mainly through moderation of ongoing drug use rather than cessation . Effect sizes were 0.37 ( 0.15 - 0.6 ) , 0.34 ( 0.09 - 0.59 ) and 0.75 ( 0.45 - 1.0 ) for reductions in the use of cigarettes , alcohol and cannabis , respectively . For both alcohol and cannabis , the effect was greater among heavier users of these drugs and among heavier cigarette smokers . The reduced cannabis use effect was also greater among youth usually considered vulnerable or high-risk according to other criteria . Change was also evident in various indicators of risk and harm , but not as widely as the changes in drug consumption . CONCLUSIONS This study provides the first substantial evidence of non-treatment benefit to be derived among young people involved in illegal drug use in receipt of motivational interviewing . The targeting of multiple drug use in a generic fashion among young people has also been supported This study consisted of a r and omized controlled trial of a 1-session motivational intervention for college student binge drinkers . Sixty students who reported binge drinking 2 or more times in the past 30 days were r and omly assigned to either a no-treatment control or a brief intervention group . The intervention provided students with feedback regarding personal consumption , perceived drinking norms , alcohol-related problems , situations associated with heavy drinking , and alcohol expectancies . At 6-week follow-up , the brief intervention group exhibited significant reductions on number of drinks consumed per week , number of times drinking alcohol in the past month , and frequency of binge drinking in the past month . Estimates of typical student drinking mediated these reductions . This study replicates earlier research on the efficacy of brief interventions with college students and extends previous work regarding potential mechanisms of change R and omized field trials provide unique opportunities to examine the effectiveness of an intervention in real world setting s and to test and extend both theory of etiology and theory of intervention . These trials are design ed not only to test for overall intervention impact but also to examine how impact varies as a function of individual level characteristics , context , and across time . Examination of such variation in impact requires analytical methods that take into account the trial 's multiple nested structure and the evolving changes in outcomes over time . The models that we describe here merge multilevel modeling with growth modeling , allowing for variation in impact to be represented through discrete mixtures -- growth mixture models-- and nonparametric smooth functions -- generalized additive mixed models . These methods are part of an emerging class of multilevel growth mixture models , and we illustrate these with models that examine overall impact and variation in impact . In this paper , we define intent-to-treat analyses in group-r and omized multilevel field trials and discuss appropriate ways to identify , examine , and test for variation in impact without inflating the Type I error rate . We describe how to make causal inferences more robust to misspecification of covariates in such analyses and how to summarize and present these interactive intervention effects clearly . Practical strategies for reducing model complexity , checking model fit , and h and ling missing data are discussed using six r and omized field trials to show how these methods may be used across trials r and omized at different levels Objective of the study is to assess the efficacy of a brief motivational enhancement intervention in adolescents referred to psychiatric treatment who reported substance-use . In a sample of adolescents ( n = 237 ) consecutively admitted to a psychiatry department , 143 were identified as users . Subjects were r and omly allocated to one of two groups : an experimental group that received a brief intervention aim ed at increasing their awareness of the risks of substance-use , or a control group . All subjects received st and ard treatment according to the primary diagnosis . Structured question naires assessing knowledge , problems , perception of risks and intention of use of psychoactive substances were administered upon admission and 1 month later . Fifty-nine subjects entered the experimental group and 44 the control group . No significant differences between the two groups were identified in socio-demographic features or substance-use . Non-parametric analyses showed a significant increase across time in overall knowledge about drugs and perception of risk in the experimental group ( P < 0.05 ) . A significant increase in overall knowledge in the experimental group compared to controls was found ( P < 0.05 ) . No differences were observed for other variables such as intention of use or perception of risk . Brief intervention in adolescents entering psychiatric treatment led to a significant change in overall knowledge about psychoactive substances but not in other variables related to use . Our results point to the need of more intensive interventions OBJECTIVE This study evaluated the relative efficacy of personalized drinking feedback ( PDF ) delivered with and without a motivational interview ( MI ) for college student drinkers . METHOD Heavy-drinking college students ( N = 54 ; 691 % female ) were identified from a large screening sample and r and omly assigned either to receive PDF during a single MI session or to receive PDF without an MI . Of these participants , 51 ( 94 % ) completed a 6-month follow-up assessment that included measures of alcohol consumption and alcohol-related problems . RESULTS At 6-months postintervention , participants in both groups showed significant , small to moderate reductions in alcohol consumption , but the groups did not differ . Women showed larger reductions than men . Rates of alcohol-related problems remained relatively unchanged . CONCLUSIONS The hypothesis that an MI would enhance the efficacy of PDF was not supported The short-term results of a r and omized trial testing a brief feedback and motivational intervention for substance use among homeless adolescents are presented . Homeless adolescents ages 14 - 19 ( N = 285 ) recruited from drop-in centers at agencies and from street intercept were r and omly assigned to either a brief motivational enhancement ( ME ) group or 1 of 2 control groups . The 1-session motivational intervention presented personal feedback about patterns of risks related to alcohol or substance use in a style consistent with motivational interviewing . Follow-up interviews were conducted at 1 and 3 months postintervention . Youths who received the motivational intervention reported reduced illicit drug use other than marijuana at 1-month follow-up compared with youths in the control groups . Treatment effects were not found with respect to alcohol or marijuana . Post hoc analyses within the ME group suggested that those who were rated as more engaged and more likely to benefit showed greater drug use reduction than did those rated as less engaged . Limitations of the study are discussed as are implication s for development of future substance use interventions for this high-risk group OBJECTIVE Behavioral economic theory suggests that a reduction in substance use is most likely when there is an increase in rewarding substance-free activities . The goal of this r and omized controlled clinical trial was to evaluate the incremental efficacy of a novel behavioral economic supplement ( Substance-Free Activity Session [ SFAS ] ) to a st and ard alcohol brief motivational interviewing ( BMI ) session for heavy-drinking college students . METHOD Participants were 82 first-year college students ( 50 % female ; 81.7 % White/European American ; M age = 18.5 years , SD = 0.71 ) who reported 2 or more past-month heavy drinking episodes . After completing a baseline assessment and an individual alcohol-focused BMI , participants were r and omized to either the SFAS or to a Relaxation Training ( RT ) control session . The SFAS was delivered in an MI style and attempted to increase the salience of delayed academic and career rewards and the patterns of behavior leading to those rewards . RESULTS The combination of an alcohol BMI plus the SFAS was associated with significantly greater reductions in alcohol problems compared with an alcohol BMI plus RT at the 1-month and 6-month follow-up assessment s ( p = .015 , ηp² = .07 ) , an effect that was partially mediated by increases in protective behavioral strategies . BMI + SFAS was also associated with greater reductions in heavy drinking among participants who at baseline reported low levels of substance-free reinforcement or symptoms of depression . CONCLUSION These results are consistent with behavioral economic theory and suggest that a single session focused on increasing engagement in alternatives to drinking can enhance the effects of brief alcohol interventions OBJECTIVE The study aim was to test whether a brief motivational intervention , with or without a booster session , would improve drinking-related outcomes more than st and ard Emergency Department ( ED ) treatment . METHOD The study population consisted of 539 ( 78 % male ) injured patients treated in the ED and discharged to the community following their treatment . Injured patients met inclusion criteria if they were assessed as hazardous or harmful drinkers by scoring eight or more on the AUDIT and /or having alcohol in their system at the time of their injury or ED visit . Patients were r and omly assigned to either st and ard care ( SC ) , brief intervention ( BI ) or brief intervention plus a booster session ( BIB ) . At 1-year follow-up , 447 patients ( 83 % of the sample ) were re-interviewed to measure alcohol-related negative consequences , injuries and drinking . RESULTS Patients receiving BIB , but not B1 patients , reduced alcohol-related negative consequences and alcohol-related injuries more than did those in the SC group . All three groups reduced their days of heavy drinking . Patients with histories of hazardous drinking responded to BIB , whether or not they had consumed alcohol prior to their injury . CONCLUSIONS Together , these results indicate that the effects of a booster session that is added to a brief intervention in the ED can be helpful to injured patients with a history of hazardous or harmful drinking , irrespective of whether they have consumed alcohol prior to their injury OBJECTIVE Brief interventions for college student drinkers have been shown to be effective in reducing the amount of alcohol consumed as well as the number of alcohol-related problems . However , the duration of brief interventions varies substantially across studies . METHOD In the present study 114 undergraduate students who drank alcohol heavily were r and omly assigned to a 10-minute brief intervention , a 50-minute brief intervention , or assessment -only control . The content of the active interventions was based on the same concept , and both interventions incorporated motivational interviewing components . Participants were assessed at baseline and 4-week post intervention on quantity of alcohol use , alcohol-related problems , and protective behavioral strategies . RESULTS As hypothesized , there was a significant difference between participants in the 10-minute intervention and control condition regarding their alcohol consumption at 4-week follow up . However , there was no significant difference between the 50-minute intervention and the control condition on alcohol consumption . There were also no significant differences between active intervention conditions , and neither intervention showed advantages for reducing problems or increasing protective behaviors relative to the control condition . CONCLUSIONS Results suggest a very brief intervention can impact short-term alcohol use outcomes , with potentially no advantage of longer interventions for this population This study evaluated the impact of a motivational interview ( MI ) on alcohol use in underage college drinkers , and examined the specific role of empathy and alliance in MI . Fifty-five underage heavy drinkers were r and omized to a one-session MI or no-treatment control . Empathy and alliance were evaluated through the MITI , participant , and therapist ratings . At two-month follow-up , multivariate tests reveal no significant interaction effects . Means comparisons indicated that both groups showed reductions in alcohol-related problems , however , only the MI sample evidence d significant reductions in binge drinking . In addition , despite the reductions of both groups , effect sizes indicated that the MI group outperformed the control in terms of binge-drinking and alcohol-related problems . Contrary to predictions , empathy and alliance showed no relationships with outcomes OBJECTIVES : Criminally involved adolescents engage in high levels of alcohol-related risky sex . A theory-based sexual and alcohol risk-reduction intervention was design ed , implemented , and evaluated in juvenile detention facilities . Participants and Methods . In a r and omized , controlled trial , 484 detained adolescents received 1 of 3 group-based interventions : combined sexual and alcohol risk reduction ( group psychosocial intervention [ GPI ] + group motivational enhancement therapy [ GMET ] ) ; sexual risk reduction only ( GPI ) ; or HIV/sexually transmitted disease prevention information only ( group information-only intervention [ GINFO ] ) . Follow-up data were obtained 3 , 6 , 9 , and 12 months after the intervention . Behavioral outcomes were condom-use behavior , frequency of intercourse while drinking , and alcohol-related problems . RESULTS : Condom-use behavior measured as frequency of condom use during sex ( ranging from never to always ) decreased over time , although the GPI and GPI + GMET interventions mitigated this tendency at the 3- , 6- , and 9-month follow-up assessment s. Although both active interventions were significantly more successful than the GINFO condition and the pattern of effects favored the GPI + GMET , there were no statistically significant differences between the GPI and GPI + GMET interventions . CONCLUSIONS : Findings support the feasibility of integrating alcohol-specific sexual risk content into a theory-based sexual risk-reduction intervention and provide additional evidence that theory-based interventions are effective at reducing risky sex in this population . There was limited evidence of intervention effects on alcohol-use outcomes . Future research should focus on strengthening the GPI + GMET to most effectively target risky sexual behavior among at-risk adolescents OBJECTIVE The current study tested the efficacy of a brief intervention design ed to reduce drinking and drinking-related consequences among first-year fraternity members . METHOD Twelve fraternities were r and omly assigned to receive either a motivational enhancement intervention with individual and housewide feedback components ( n = 6 houses ) or a treatment-as-usual control condition ( n = 6 houses ) . Individual feedback was delivered either by peer interviewers or professional research staff . Participants were assessed during their pledge ( first ) year of house membership and during a follow-up period 1 year later . RESULTS Of the participants who completed follow-up ( N = 120 ) , fraternity members who received the brief intervention reported significant reductions in alcohol use ( total average consumption ) and typical peak blood alcohol concentrations when compared with fraternity members in the control condition . No differences in drinking-related consequences were observed . Fraternity members who received their individualized feedback from peer interviewers and professional members of the research staff reported similar outcomes . CONCLUSIONS Results provide support for the efficacy of a brief motivational enhancement intervention in reducing drinking within this high-risk population . The cost-effective use of peer interviewers appears to be a promising strategy for delivering individualized prevention programming in college population OBJECTIVE College students are an at-risk population for heavy drinking and negative alcohol-related outcomes . Research has established that brief , multicomponent motivational interviewing-based interventions can be effective at reducing alcohol use or related problems , but less is known about the efficacy of individual components within these interventions . The purpose of this study was to test the efficacy of 2 single-component , in-person , brief ( 15 - 20 min ) alcohol interventions : personalized normative feedback ( PNF ) and protective behavioral strategies feedback ( PBSF ) . METHOD Data were collected on 365 undergraduate students from a large Midwestern university ( 65 % women ; 89 % White ) who were r and omly assigned to 1 of 3 conditions : PNF , PBSF , or alcohol education ( AE ) . Participants completed measures of alcohol use , alcohol-related problems , social norms , and protective behavioral strategies . RESULTS Results indicated that the PNF intervention was efficacious relative to the other conditions at reducing alcohol use and that its effects at 6-month follow-up were mediated by changes in perceived norms at the 1-month follow-up . The PBSF intervention was not efficacious at reducing alcohol use or alcohol-related problems . CONCLUSIONS These findings provide support for the efficacy of an in-person PNF intervention and theoretical support for the hypothesized mechanisms of change in the intervention . Implication s for research ers and clinicians are discussed R. Lorraine Collins State University of New York at Stony Brook George A. Parks and G. Alan Marlatt University of Washington Two studies were conducted to assess variables related to the social determinants of alcohol consumption . In Study 1 , moderate- and heavy-drinking male under- graduates were paired with confederates who behaved in a sociable or unsociable manner while modeling either light or heavy consumption . Modeling occurred in the sociable conditions but not in the unsociable conditions , where subjects tended to drink heavily . In Study 2 , a similar group of subjects was exposed to one of three social status conditions crossed with light versus heavy consumption . The results indicated a modeling effect in all social status conditions . These studies provide further support for the existence of a modeling effect that can be disrupted by a lack of rapport between drinking partners . This latter finding has implication s for the etiology of problem drinking because it suggests that increased alcohol consumption may serve as a strategy for coping with aversive social interactions . Initial research on the effect of modeled consumption rates on social drinking ( Caudill & Marlatt , 1975 ) suggested that heavy-drink- ing men tended to match the consumption of their drinking partner whether his con- sumption was heavy or light . Subsequent examinations of this phenomenon replicated these findings in laboratory analogue drinking tasks such as the taste-rating task ( Cooper , Waterhouse , & Sobell , 1979 ; Hendricks , So- bell , & Cooper , 1978 ; Lied & Marlatt , 1979 ; Watson & Sobell , 1982 ) , natural bar setting s ( Reid , 1978 ) , and seminaturalistic bar setting s ( Caudill & Lipscomb , 1980 ) . Much of the research concerning the mod- eling of alcohol consumption has focused on manipulating characteristics of the model , including the nature of the social interaction between the model and the subject . The effects of manipulating social interaction are unclear . In the Caudill and Marlatt study , model 's drinking rate ( light vs. heavy ) and OBJECTIVE Using a r and omized factorial design , we examined the efficacy of a brief motivational intervention ( BMI ) and a parent-based intervention ( PBI ) as universal preventive interventions to reduce alcohol use among incoming college students . METHOD Participants ( N = 1,014 ) were assessed prior to matriculation and at 10 months and 22 months postbaseline . Two-part latent growth modeling was used to simultaneously examine initiation and growth in heavy episodic drinking and alcohol-related consequences . RESULTS This study retained 90.8 % ( n = 921 ) of r and omized students at the 10-month follow-up and 84.0 % ( n = 852 ) of r and omized students at the 22-month follow-up . BMI participants were significantly less likely than non- BMI participants to initiate heavy episodic drinking and to begin experiencing alcohol-related consequences . Effect sizes were minimal at 10 months ( Cohen 's h ranged from 0.02 to 0.07 ) and were small at 22 months ( hs ranged from 0.15 to 0.22 ) . A significant BMI x PBI interaction revealed that students receiving both the BMI and the PBI were significantly less likely to report the onset of consequences beyond the sum of the individual intervention effects ( h = 0.08 at 10 months , and h = 0.21 at 22 months ) . Hypothesized direct BMI effects for reductions in heavy episodic drinking and consequences were not observed . Significant mediated effects via changes in descriptive norms were present for both growth and initiation of heavy episodic drinking and consequences . CONCLUSIONS To our knowledge , the current study is the first to provide support for BMI as a universal preventive intervention for incoming college students . Although hypothesized PBI main effects were not found , mediation analyses suggest future refinements could enhance PBI effectiveness We tested whether a brief motivational interview ( MI ) would reduce alcohol-related consequences and use among adolescents treated in an emergency department ( ED ) after an alcohol-related event . Patients aged 13 to 17 years ( N = 152 ) with a positive blood alcohol concentration ( BAC ) by lab test or self-report were recruited in the ED and r and omly assigned to receive either MI or st and ard care ( SC ) . Both conditions result ed in reduced quantity of drinking during the 12-month follow-up , whereas alcohol-related negative consequences were relatively low and stayed low at follow-up . Adolescents who screened positive for problematic alcohol use at baseline reported significantly more improvement on 2 of 3 alcohol use outcomes ( average number of drinking days per month and frequency of high-volume drinking ) if they received MI compared with SC . We conclude that brief interventions are recommended for adolescents who present to an ED with an alcohol-related event and report preexisting problematic alcohol use BACKGROUND Drug use among parenting women is a significant risk factor for a range of negative child outcomes , including exposure to violence , child maltreatment , and child behavior problems . Implementation of brief interventions with this population may be greatly facilitated by computer-based interventions . DESIGN R and omized clinical trial with 4-month follow-up . SETTING / PARTICIPANTS Participants were 107 postpartum women recruited from an urban obstetric hospital primarily serving a low-income population . Women were r and omized into assessment only versus assessment plus brief intervention conditions ; 76 ( 71 % ) returned for follow-up evaluation . INTERVENTION A 20-minute , single-session , computer-based motivational intervention ( based on motivational interviewing methods ) , combined with two nontailored mailings and voucher-based reinforcement of attendance at an initial intake/treatment session . MAIN OUTCOME MEASURES Illicit drug use as measured by qualitative urinalysis and self-report . RESULTS Frequency of illicit drug use other than marijuana increased slightly for the control group , but declined among intervention group participants ( p<0.05 , between-group Mann-Whitney U ; d=0.50 ) ; the magnitude of intervention effects on changes in marijuana use frequency was similar , but did not reach statistical significance . Point-prevalence analysis at follow-up did not show significant group differences in drug use . However , trends under a range of assumptions regarding participants lost to follow-up all favored the intervention group , with most effect sizes in the moderate range ( odds ratios 1.4 to 4.7 ) . CONCLUSIONS Results tentatively support the efficacy of this high-reach , replicable brief intervention . Further research should seek to replicate these findings and to further develop the computer as a platform for vali date d brief interventions Heavy drinking among college students is common and is often harmful . A previously reported r and omized trial revealed that a brief motivational intervention ( BMI ) reduced the alcohol consumption of heavy drinking college students ( K. B. Carey , M. P. Carey , S. A. Maisto , & J. M. Henson , 2006 ) . For this study , the research ers conducted supplemental analyses of hypothesized predictors of change using the same sample ( N = 495 ) . Greater readiness to change , higher levels of self-regulation , and less engagement in social comparison all independently predicted reductions in drinking outcomes . Furthermore , self-regulation , social comparison , and future time perspective interacted with BMI and predicted drinks per week . As expected , greater self-regulation skills enhanced response to the BMI ; the remaining interaction effects were unexpected . Overall , these findings suggest that BMI s produce relatively robust effects OBJECTIVE The current study is a multisite r and omized alcohol prevention trial to evaluate the efficacy of both a parenting h and book intervention and the Brief Alcohol Screening and Intervention for College Students ( BASICS ) intervention , alone and in combination , in reducing alcohol use and consequences among a high-risk population of matriculating college students ( i.e. , former high school athletes ) . METHOD Students ( n = 1,275 ) completed a series of Web-administered measures at baseline ( in the summer before starting college ) and follow-up ( after 10 months ) . Students were r and omized to one of four conditions : parent intervention only , BASICS only , combined ( parent and BASICS ) , and assessment -only control . Intervention efficacy was tested on a number of outcome measures , including peak blood alcohol concentration , weekly and weekend drinking , and negative consequences . Hypothesized mediators and moderators of intervention effect were tested . RESULTS The overall results revealed that the combined-intervention group had significantly lower alcohol consumption , high-risk drinking , and consequences at 10-month follow-up , compared with the control group , with changes in descriptive and injunctive peer norms mediating intervention effects . CONCLUSIONS The findings of the present study suggest that the parent intervention delivered to students before they begin college serves to enhance the efficacy of the BASICS intervention , potentially priming students to respond to the subsequent BASICS session OBJECTIVES This study examined long-term response to an individual preventive intervention for high-risk college drinkers relative to the natural history of college drinking . METHODS A single-session , individualized preventive intervention was evaluated within a r and omized controlled trial with college freshmen who reported drinking heavily while in high school . An additional group r and omly selected from the entire screening pool provided a normative comparison . Participant self-report was assessed annually for 4 years . RESULTS High-risk controls showed secular trends for reduced drinking quantity and negative consequences without changes in drinking frequency . Those receiving the brief preventive intervention reported significant additional reductions , particularly with respect to negative consequences . Categorical individual change analyses show that remission is normative , and they suggest that participants receiving the brief intervention are more likely to improve and less likely to worsen regarding negative drinking consequences . CONCLUSIONS Brief individual preventive interventions for high-risk college drinkers can achieve long-term benefits even in the context of maturational trends OBJECTIVE Brief interventions for hazardous and low-dependent drinkers in the primary care setting have considerable empirical support . The purpose of this study was to ( 1 ) evaluate the effects of brief advice ( BA ) and motivational enhancement ( ME ) interventions on alcohol consumption . In addition , a hindsight matching design was used to ( 2 ) study the moderator effects of patient readiness to change ( alcohol use ) on alcohol consumption . METHOD The subjects ( N = 301 , 70 % men ) were patients 21 years of age or older who presented for treatment at one of 12 primary care clinics . After screening for eligibility and providing consent to participate in the study , the patients completed a baseline assessment and were r and omly assigned to the BA , ME or st and ard care ( SC ) interventions condition . Follow-up assessment s were completed at 1- , 3- , 6- , 9- and 12-months postbaseline assessment . RESULTS Evaluation of the first hypothesis ( n = 232 for these analyses ) showed that all participants tended to reduce their alcohol use considerably between the baseline and 12-month assessment s. In addition , evaluation of the second hypothesis showed a moderator effect of readiness to change in predicting the number of drinks at 12 months , such that the BA intervention seemed more effective for patients relatively low in readiness to change compared to those higher in readiness . Readiness to change did not seem to be related to changes in drinking of participants in the SC or ME conditions . CONCLUSIONS The results confirm that , among primary care patients , substantial changes in alcohol consumption are possible . They further suggest that matching studies of patient readiness to change their alcohol use , as well as other variables , are warranted The present study tested the proposition that an intervention to reduce alcohol use among college students will also reduce their risky sexual behavior . In a r and omized controlled trial , 154 heavy-drinking , predominantly White , heterosexual college students at behavioral risk for infection with HIV and other sexually transmitted diseases were assigned to receive no intervention or a two-session , in-person , motivational interviewing-based intervention focused on ( a ) reducing alcohol risk behavior , ( b ) reducing HIV risk behavior , or ( c ) reducing both alcohol and HIV risk behavior . Three-month retrospective assessment s of alcohol use and sexual behavior were conducted at intake and at 3- , 6- , 9- , 12- , and 15-month follow-up appointments . During follow-up , participants who received the single-focus alcohol risk-reduction intervention drank less frequently and consumed fewer drinks per drinking day as compared with no-intervention control participants , but did not differ from control participants in their frequency of intercourse without a condom or number of sexual partners . Participants who received the single-focus HIV risk-reduction intervention evidence d fewer unprotected sex events during follow-up , as compared with control participants . The number of sexual partners reported during follow-up did not differ by condition . Effects of the interventions did not vary significantly over time and were not moderated by participant gender . Results suggest that intervening to reduce alcohol use may not reduce risky sexual behavior among nonminority college students , but that a brief motivational intervention targeting HIV risk behavior may have utility for reducing the frequency of unprotected sex in this population BACKGROUND It is known that brief interventions for m and ated college students decrease alcohol use and /or related problems in the short term . However , none of the existing studies has followed students ' past 6 months . Therefore , we compared the long-term efficacy of 2 brief substance use feedback interventions for m and ated college students . METHODS We followed up m and ated students ( N=348 ) who were r and omly assigned to either a brief motivational interview ( BMI ; n=180 ) or a written feedback-only ( WF ; n=168 ) intervention at 4 months and 15 months postintervention . RESULTS Long-term follow-up data revealed that students , at the aggregate level , decreased their peak blood alcohol concentration ( BAC ) levels , number of drinks per week , and number of alcohol-related problems at 15 months postintervention compared with their baseline levels . With the exception of peak BAC , the observed long-term reduction was mainly due to the positive change among students who received the BMI intervention . Students in the BMI intervention showed significantly lower levels of alcohol-related problems at 15 months than those in the WF intervention . The BMI intervention more effectively reduced within-individual alcohol-related problems during the initial 4 months , and more successfully curbed the subsequent increase in alcohol use frequency and number of drinks per week during the 11 months between the 2 follow-up assessment s. CONCLUSIONS The results suggest that brief substance use interventions reduce the riskiest type of alcohol use ( e.g. , peak BAC ) among m and ated college students over the long term , and that sleeper effects of in-person personal feedback interventions ( PFIs ) exist . In-person PFIs in the context of a motivational interview may be more efficacious in the long term than written feedback-only interventions for m and ated students . Future studies comparing interventions for college students should extend follow-up for longer periods of time This study evaluated the efficacy of an alcohol web-based personalized feedback program delivered in the workplace to young adults . Participants ( N = 124 ) were r and omly assigned to one of three conditions : web-based feedback ( WI ) , web-based feedback plus a 15-minute motivational interviewing session ( MI ) , or a control group . Results indicated that participants in the intervention group ( WI and MI conditions combined ) reported significantly lower levels of drinking than those in the control group at a 30-day follow-up . This was particularly true for participants classified as high-risk drinkers at the baseline assessment . Similar results were found when comparing the WI condition to the control group . No differences were found between the WI and MI conditions , indicating that the addition of a 15-minute motivational interviewing session did not increase the efficacy of the web-based feedback program . Findings support the use of web-based feedback as a st and -alone alcohol prevention program for young adults in the workplace The purpose of this study was to evaluate the efficacy of two brief interventions and the inclusion of a 1-month booster session with college students who were referred to attend alcohol education following an alcohol-related incident . Participants ( N=225 ; 48.9 % male ) were r and omly assigned to receive one session of a Brief Motivational Interview ( BMI ) or computer-delivered intervention ( CDI ) with the Alcohol 101 CD-ROM . Participants were also r and omly assigned to booster/no booster . At 3-month follow up , participants in BMI reported greater help seeking and use of behavioral strategies to moderate drinking . At 12-month follow up , BMI participants were drinking more frequently and CDI participants were consuming a greater number of drinks per occasion than at baseline . Mediation analyses showed that the use of specific behavioral strategies mediated the effect of the BMI condition on drinking volume . There was no intervention effect on alcohol problems , and the booster condition did not significantly affect outcomes . Promoting specific behaviors in the context of in-person brief interventions may be a promising approach to reducing drinking volume among identified at-risk students This study evaluated the use of a brief motivational interview ( MI ) to reduce alcohol-related consequences and use among adolescents treated in an emergency room ( ER ) following an alcohol-related event . Patients aged 18 to 19 years ( N = 94 ) were r and omly assigned to receive either MI or st and ard care ( SC ) . Assessment and intervention were conducted in the ER during or after the patient 's treatment . Follow-up assessment s showed that patients who received the MI had a significantly lower incidence of drinking and driving , traffic violations , alcohol-related injuries , and alcohol-related problems than patients who received SC . Both conditions showed reduced alcohol consumption . The harm-reduction focus of the MI was evident in that MI reduced negative outcomes related to drinking , beyond what was produced by the precipitating event plus SC alone The authors conducted two r and omized clinical trials with ethnically diverse sample s of college student drinkers in order to determine ( a ) the relative efficacy of two popular computerized interventions versus a more comprehensive motivational interview approach ( BASICS ) and ( b ) the mechanisms of change associated with these interventions . In Study 1 , heavy drinking participants recruited from a student health center ( N = 74 , 59 % women , 23 % African American ) were r and omly assigned to receive BASICS or the Alcohol 101 CD-ROM program . BASICS was associated with greater post-session motivation to change and self-ideal and normative discrepancy relative to Alcohol 101 , but there were no group differences in the primary drinking outcomes at 1-month follow-up . Pre to post session increases in motivation predicted lower follow-up drinking across both conditions . In Study 2 , heavy drinking freshman recruited from a core university course ( N = 133 , 50 % women , 30 % African American ) were r and omly assigned to BASICS , a web-based feedback program ( e-CHUG ) , or assessment -only . BASICS was associated with greater post-session self-ideal discrepancy than e-CHUG , but there were no differences in motivation or normative discrepancy . There was a significant treatment effect on typical weekly and heavy drinking , with participants in BASICS reporting significantly lower follow-up drinking relative to assessment only participants . In Study 2 , change in the motivation or discrepancy did not predict drinking outcomes . Across both studies , African American students assigned to BASICS reported medium effect size reductions in drinking whereas African American students assigned to Alcohol 101 , e-CHUG , or assessment did not reduce their drinking AIMS To investigate whether a stimulant- and alcohol-focused brief motivational intervention induces positive behaviour change among young , regular users of MDMA ( ' ecstasy ' ) , cocaine powder and crack cocaine . DESIGN AND MEASUREMENTS A r and omized trial of the intervention versus a control group who received written health risk information material s only . All participants completed a baseline self- assessment question naire before r and omization . Outcome measures were self-reported period prevalence abstinence from ecstasy , cocaine powder and crack cocaine and the frequency and amount of stimulant and alcohol use in the previous 90 days , recorded at 6-month follow-up via self-completion question naire and personal interview . PARTICIPANTS AND SETTING A total of 342 adolescent and young adult stimulant users ( aged 16 - 22 years ) were recruited and 87 % were followed-up . The intervention was delivered by a team of 12 agency youth drug workers and two research ers at five locations in Greater London and south-east Engl and . FINDINGS There were no significant differences in abstinence for ecstasy , cocaine powder or crack cocaine use between the experimental and control groups . Contrasting follow-up with baseline self-reports , there were no between-group effects for changes in the frequency or amount of stimulant or alcohol use . Participant follow-up data suggested that the baseline assessment was a contributing factor in within-group behaviour change among experimental and control condition participants . CONCLUSIONS Our brief motivational intervention was no more effective at inducing behaviour change than the provision of information alone . We hypothesize that research recruitment , baseline self- assessment and contact with study personnel are influences that induce positive reactive effects on stimulant use Encouraging but limited research indicates that brief motivational interventions may be an effective way to reduce heavy episodic drinking in college students . At 2 campuses , students ( 83 % male ) m and ated to a substance use prevention program were r and omly assigned to 1 of 2 individually administered conditions : ( a ) a brief motivational interview ( BMI ; n = 34 ) or ( b ) an alcohol education session ( AE ; n = 30 ) . Students in the BMI condition reported fewer alcohol-related problems than the AE students at 3- and 6-month assessment s. Trends toward reductions in number of binge drinking episodes and typical blood alcohol levels were seen in both groups . Process measures confirmed the integrity of both interventions . The findings demonstrate that m and ated BMI s can reduce alcohol problems in students referred for alcohol violations OBJECTIVE The aim of this study was to test the efficacy of brief physician advice in reducing alcohol use and related harm in college students . METHOD The College Health Intervention Projects ( CHIPs ) is a r and omized , controlled clinical trial with 12-month follow-up conducted in five college health clinics in Wisconsin ; Washington state ; and Vancouver , Canada . Of the 12,900 students screened for high-risk drinking , 484 men and 502 women met inclusion criteria and were r and omized into a control ( n = 493 ) or intervention ( n = 493 ) group . Ninety-six percent of students participated in the follow-up procedures . The intervention consisted of two 15-minute counseling visits and two follow-up phone calls , and used motivational interviewing , contracting , diary cards , and take-home exercises . RESULTS No significant differences were found between groups at baseline on alcohol use , age , socioeconomic or smoking status , rates of depression , or measures of alcohol-related harm . At 12 months , the experimental subjects reduced their 28-day drinking totals by 27.2 % , and the control group reduced their totals by 21 % . A mixed effects repeated measures model found a statistical difference in favor of the brief-intervention group ( beta = 4.7 , SE = 2.0 , p = .018 ) in 28-day drinking totals . The total Rutgers Alcohol Problem Index score was also significantly different during the 12-month follow-up period ( beta = 0.8 , SE = 0.4 , p = .033 ) . There was no difference on the other outcome measures of interest , such as frequency of excessive heavy drinking , health care utilization , injuries , drunk driving , depression , or tobacco use . CONCLUSIONS The study supports re source allocation and implementation of alcohol screening and brief physician advice in primary care-based college health clinics AIM To evaluate the effectiveness of a brief motivational intervention on alcohol consumption and misuse in young males with alcohol-related face injury . DESIGN R and omized controlled trial . SETTING Oral and maxillofacial surgery out-patient clinic in an urban teaching hospital . PARTICIPANTS One hundred and fifty-one participants were r and omized to motivational intervention and control conditions . INTERVENTIONS Control was treatment as usual . The intervention was treatment as usual plus a one-session brief motivational intervention administered by a nurse . MEASUREMENTS Three sets of measurements were taken at baseline , 3-month and 1-year follow-up . Collateral measurements were also taken at 1-year follow-up . Primary outcome measures were total alcohol consumption , typical weeks consumption and days abstinent in preceding 3 months . Other outcome measures included the Alcohol Use Disorders Identification Test , a short form of the Alcohol Problems Question naire , and a measure of satisfaction with social relationships . RESULTS There was a significant decrease in 84-day total alcohol consumption across the year ( P < 0.006 ) and further , a significant effect for the motivational intervention was demonstrated ( P < 0.029 ) . This pattern was repeated for days abstinent and alcohol consumption in a typical week as well as alcohol-related problems . There was a significantly greater reduction in the percentage of hazardous drinkers in the motivational intervention group ( from 60 % to 27 % , P < 0.009 ) compared to the control group ( from 54 % to 51 % , NS ) . CONCLUSION A proportion of young men change their alcohol consumption following alcohol-related injury . A nurse-led psychological intervention adds significantly to the proportion and magnitude of response In this r and omized controlled trial , the authors evaluated brief motivational interventions ( BMI s ) for at-risk college drinkers . Heavy drinking students ( N = 509 ; 65 % women , 35 % men ) were r and omized into 1 of 6 intervention conditions formed by crossing the baseline Timeline Followback ( TLFB ) interview ( present versus absent ) and intervention type ( basic BMI , BMI enhanced with a decisional balance module , or none ) . Assessment s completed at baseline , 1 , 6 , and 12 months measured typical and risky drinking as well as drinking-related problems . Relative to controls , the TLFB interview reduced consumption but not problems at 1 month . The basic BMI improved all drinking outcomes beyond the effects of the TLFB interview at 1 month , whereas the enhanced BMI did not . Risk reduction achieved by brief interventions maintained throughout the follow-up year The current study examined the impact of a brief motivational interviewing ( MI ) intervention ( Project CHAT ) on alcohol consumption and drug use for high-risk teens in a primary care clinic that provides health care for underserved population s. Youth ( N=42 , 48 % male ) were screened , and those eligible completed a baseline survey . Baseline survey completers were r and omly assigned to usual care or to an MI intervention and completed a 3-month follow-up survey . The sample ( age 12 to 18 years ) was 85.7 % Hispanic or Latino , 9.5 % African American , and 4.8 % White . At the 3-month follow-up , Project CHAT teens reported less marijuana use , lower perceived prevalence of marijuana use , fewer friends who used marijuana , and lower intentions to use marijuana in the next 6 months , as compared to teens assigned to usual care . Providing this type of brief intervention is a viable approach to working with high-risk teens to decrease substance use This study assessed the impact of a motiv ational interv iewing ( MI ) brief alcohol interv ention and prior v ictimization on alcohol-inv olv ed sexual v ictimization experiences . First-year female college students ( N = 229 ) were r and omly assigned to an interv ention condition : MI , MI with feedback ( MIFB ) , feedback ( FB ) , and assessment only ( AO ) . Findings indicate reduced alcohol use for all conditions and v iolence for MIFB , with interactions for prior v ictimization . The mechanism of change for reduced v ictimization was not reductions in alcohol use and mechanisms for this effectiv eness remain somewhat conv oluted . Tailoring of brief interv entions addressing alcohol use and sexual v iolence , particularly for women with prior v ictimization , is critical Motivational interviewing ( MI ) has been found to be an effective treatment for substance using population s , including incarcerated adolescents . Although some studies suggest MI is more successful with individuals from minority background s , the research remains mixed . The current study investigated the impact of ethnicity on treatment in reducing alcohol and marijuana use among incarcerated adolescents . Adolescents ( 14 - 19 years of age ) were recruited from a state juvenile correctional facility and r and omly assigned to receive MI or relaxation therapy ( RT ) ( N=147 ; 48 White , 51 Hispanic , and 48 African American ; 126 male ; 21 female ) . Interviews were conducted at admission to the facility and 3 months after release . Results suggest that the effects of MI on treatment outcomes are moderated by ethnicity . Hispanic adolescents who received MI significantly decreased total number of drinks on heavy drinking days ( NDHD ) and percentage of heavy drinking days ( PHDD ) as compared to Hispanic adolescents who received RT . These findings suggest that MI is an efficacious treatment for an ethnic minority juvenile justice-involved population in need of evidence -based treatments CONTEXT Emergency department ( ED ) visits present an opportunity to deliver brief interventions to reduce violence and alcohol misuse among urban adolescents at risk of future injury . OBJECTIVE To determine the efficacy of brief interventions addressing violence and alcohol use among adolescents presenting to an urban ED . DESIGN , SETTING , AND PARTICIPANTS Between September 2006 and September 2009 , 3338 patients aged 14 to 18 years presenting to a level I ED in Flint , Michigan , between 12 pm and 11 pm 7 days a week completed a computerized survey ( 43.5 % male ; 55.9 % African American ) . Adolescents reporting past-year alcohol use and aggression were enrolled in a r and omized controlled trial ( SafERteens ) . INTERVENTION All patients underwent a computerized baseline assessment and were r and omized to a control group that received a brochure ( n = 235 ) or a 35-minute brief intervention delivered by either a computer ( n = 237 ) or therapist ( n = 254 ) in the ED , with follow-up assessment s at 3 and 6 months . Combining motivational interviewing with skills training , the brief intervention for violence and alcohol included review of goals , tailored feedback , decisional balance exercise , role plays , and referrals . MAIN OUTCOME MEASURES Self-report measures included peer aggression and violence , violence consequences , alcohol use , binge drinking , and alcohol consequences . RESULTS About 25 % ( n = 829 ) of screened patients had positive results for both alcohol and violence ; 726 were r and omized . Compared with controls , participants in the therapist intervention showed self-reported reductions in the occurrence of peer aggression ( therapist , -34.3 % ; control , -16.4 % ; relative risk [ RR ] , 0.74 ; 95 % confidence interval [ CI ] , 0.61 - 0.90 ) , experience of peer violence ( therapist , -10.4 % ; control , + 4.7 % ; RR , 0.70 ; 95 % CI , 0.52 - 0.95 ) , and violence consequences ( therapist , -30.4 % ; control , -13.0 % ; RR , 0.76 ; 95 % CI , 0.64 - 0.90 ) at 3 months . At 6 months , participants in the therapist intervention showed self-reported reductions in alcohol consequences ( therapist , -32.2 % ; control , -17.7 % ; odds ratio , 0.56 ; 95 % CI , 0.34 - 0.91 ) compared with controls ; participants in the computer intervention also showed self-reported reductions in alcohol consequences ( computer , -29.1 % ; control , -17.7 % ; odds ratio , 0.57 ; 95 % CI , 0.34 - 0.95 ) . CONCLUSION Among adolescents identified in the ED with self-reported alcohol use and aggression , a brief intervention result ed in a decrease in the prevalence of self-reported aggression and alcohol consequences . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00251212 OBJECTIVE The aim of this research was to study marijuana use , associated risks , and response to brief motivational intervention among young adult drinkers treated in an emergency department . METHOD Study participants ( N = 215 ; ages 18 - 24 ) were in a r and omized controlled trial for alcohol use that compared motivational interviewing with personalized feedback ( MI ) with personalized feedback only . Past-month marijuana users were compared with nonusers on demographics , readiness , self-efficacy , and behavioral risk variables . Marijuana use was examined as a potential moderator of alcohol outcomes . Whether marijuana use alone or combined marijuana and alcohol use would be reduced as a result of brief intervention for alcohol was examined at 6 and 12 months . RESULTS Current marijuana users were younger , were more likely to be white , and reported more alcohol use , other illicit drug use , and more alcohol-related consequences than nonmarijuana users . Marijuana use at baseline did not moderate response to brief alcohol treatment . Marijuana use declined from baseline to 6 months for both treatment groups , but only MI participants continued to reduce their use of marijuana from 6- to 12-month follow-up . Reductions in number of days of use of marijuana with alcohol appeared to be primarily a function of decreased alcohol use . CONCLUSIONS Young adult drinkers reporting current marijuana use are at generally higher risk but responded to brief alcohol treatment by reducing alcohol and marijuana use AIMS College students who violate alcohol policies are often m and ated to participate in alcohol-related interventions . This study investigated ( i ) whether such interventions reduced drinking beyond the sanction alone , ( ii ) whether a brief motivational intervention ( BMI ) was more efficacious than two computer-delivered interventions ( CDIs ) and ( iii ) whether intervention response differed by gender . DESIGN R and omized controlled trial with four conditions [ brief motivation interventions ( BMI ) , Alcohol 101 Plus ™ , Alcohol Edu for Sanctions ( ® ) , delayed control ] and four assessment s ( baseline , 1 , 6 and 12 months ) . SETTING Private residential university in the United States . PARTICIPANTS Students ( n = 677 ; 64 % male ) who had violated campus alcohol policies and were sanctioned to participate in a risk reduction program . MEASUREMENTS Consumption ( drinks per heaviest and typical week , heavy drinking frequency , peak and typical blood alcohol concentration ) , alcohol problems and recidivism . FINDINGS Piecewise latent growth models characterized short-term ( 1-month ) and longer-term ( 1 - 12 months ) change . Female but not male students reduced drinking and problems in the control condition . Males reduced drinking and problems after all interventions relative to control , but did not maintain these gains . Females reduced drinking to a greater extent after a BMI than after either CDI , and maintained reductions relative to baseline across the follow-up year . No differences in recidivism were found . CONCLUSIONS Male and female students responded differently to sanctions for alcohol violations and to risk reduction interventions . BMI s optimized outcomes for both genders . Male students improved after all interventions , but female students improved less after CDIs than after BMI . Intervention effects decayed over time , especially for males This study piloted a brief individual motivational intervention targeting multiple health risk behaviors in HIV-positive youth aged 16 - 25 . Interviews about sexual behavior and substance use and viral load testing were obtained from 51 HIV-positive youth at baseline and post intervention . Youth were r and omized to receive a four-session motivational enhancement intervention ( N = 25 ) or to a wait-list control ( N = 26 ) . Of the eligible youth approached , 88 % agreed to participate , and 80 % percent of participants completed at least three of four sessions . The treatment group showed significantly greater reductions in unprotected sex acts and in viral load compared with controls . Although change scores for substance use were not significantly different between the two groups , paired t tests demonstrated that reductions in alcohol use and marijuana use were significant for the treatment group at the trend level . There were no significant differences in substance use from baseline to posttest for the control group . Findings demonstrate the potential of a brief motivational enhancement intervention to improve health risk behaviors in HIV-positive youth . Larger r and omized clinical trials are warranted . Re sources required for retention should not be underestimated Research indicates that motivational enhancement therapy ( MET ) helps catalyze reductions in problem drinking among emerging adults . However , moderators of this intervention remain relatively unknown . Therefore , the objectives of this study were : ( 1 ) to test whether a single session of MET increased motivation to reduce drinking and drinking outcomes ; and ( 2 ) to examine whether genetic dopamine D4 receptor L ( DRD4 L ) and individual personality risk factors ( impulsivity and novelty seeking ) moderated the effects of the MET . These hypotheses were evaluated by r and omly assigning a sample of emerging adult problem drinkers ( n = 67 ) to receive a single session of MET or alcohol education . Follow‐up data indicated that only individuals who were low in impulsivity , novelty seeking and /or who had the short DRD4 variable number of t and em repeats genotype evidence d differentially increased behavior change ( taking steps toward reducing drinking ) following the MET Motivational Interviewing ( MI ) to reduce alcohol and marijuana-related driving events among incarcerated adolescents was evaluated . Adolescents were r and omly assigned to receive MI or Relaxation Training . Follow-up assessment showed that , as compared to RT , adolescents who received MI had lower rates of drinking and driving , and being a passenger in a car with someone who had been drinking . Effects were moderated by levels of depression . At low levels of depression , MI evidence d lower rates of these behaviors ; at high levels of depression , effects for MI and RT were equivalent . Similar patterns were found for marijuana-related risky driving , but effects were non-significant AIM To test the effectiveness of motivational interviewing ( MI ) in comparison with drug information and advice in opportunistically securing reductions in drug-related risk among young cannabis users not seeking help . DESIGN R and omized controlled trial . SETTING Eleven London Further Education colleges . PARTICIPANTS A total of 326 students aged 16 - 19 years who smoked cannabis weekly or more frequently . INTERVENTIONS Participants were r and omized to a single-session intervention of MI or drug information and advice-giving . MEASUREMENTS Cannabis use , cigarette smoking and alcohol consumption and harm outcomes were assessed after both 3 and 6 months . FINDINGS No differences were found between MI and drug information and advice , although MI fidelity was not high . There were wide-ranging individual practitioner effects on observed outcomes and a practitioner-intervention interaction was detected in relation to cannabis cessation after 3 months . Change over time was more pronounced for cannabis use than for other drug use . CONCLUSIONS Further study of the nature and consequences of MI fidelity , and individual practitioner effects more generally , is needed . Advice may be an effective brief intervention with young cannabis users in its own right and should be evaluated further in trials |
1,632 | 30,654,775 | Conclusion Exercise showed large effects , while acupressure and heat showed moderate effects in reducing menstrual pain compared to no treatment .
Both exercise and heat are potential alternatives to analgesic medication . | Background Menstrual pain is very common amongst young women .
Despite the significant impact that menstrual pain has on academic attendance and performance , social activities and quality of life , most young women do not seek medical treatment but prefer to use self-care ; commonly OTC analgesic medications and rest .
Many women do not get significant pain relief from these methods , therefore other low cost , easy to learn self-care methods may be a valuable approach to management .
This review and meta- analysis examines the evidence for participant lead self-care techniques . | OBJECTIVES This is a controlled , prospect i ve study which compares the effects of a low-dose heat patch for self-medication on the reduction of pain symptoms in dysmenorrhea . METHODS The sample group included female sophomore students study ing at a university in Istanbul , Turkey , between 2007 and 2008 . These female participants completed the Dysmenorrhea Identification Form to determine the sample group , and a total of 193 female students possessed the eligible criteria . The research control group consisted of 66 patients , the analgesia group consisted of 61 , and the heat patch group consisted of 66 . The control group did not use any treatments , while the self-medication group used analgesic medication ( single dose ) , and the heat patch group applied a heat patch on the lower abdomen , against the skin , for an application period of 2 menstrual cycles . Using a visual analog scale ( VAS ) , the pain severity was recorded at the baseline , after 4 hours of intervention , and after 8 hours of intervention . The data were examined using ANOVA . RESULTS There were significant differences between the groups in terms of pain severity after 8 hours of application ( P < .001 ) . All groups had similar pain levels at baseline and during the fourth and eighth hours , with no significant differences between the groups during the first and the second menstrual cycles ( P > .05 ) . CONCLUSION The authors conclude that the heat patch is an effective method for reducing dysmenorrhea OBJECTIVES The aim of this study was to evaluate the effects of auricular acupressure on relieving menstrual symptoms and decreasing nitric oxide ( NO ) for women with primary dysmenorrhea . DESIGN This was a r and omized clinical trial comparing the effects of auricular acupressure by seed-pressure method and placebo adhesive patch . SETTING Setting s included colleges in northern and central Taiwan . SUBJECTS Serum CA-125 testing was used as a screening test for primary dysmenorrhea ( < 35 mg/dL ) . The study included 36 college females r and omized to acupressure group , 35 to control group . INTERVENTIONS The acupressure group received auricular acupressure by seed-pressure method on liver ( CO12 ) , kidney ( CO10 ) , and endocrine ( CO18 ) acupoints . The control group had a plain adhesive patch placed on the same acupoints with no seed attached . Acupressure protocol included massaging 15 times on each acupoint , 3 times a day , for a total of 20 days . OUTCOME MEASURES Primary : Short-form Menstrual Distress Question naire ( MDQs ) . Secondary : blood sample of NO . Assessment s of MDQs and NO were performed at baseline and within the first 2 days of their next menses ( after completion of 20 days of acupressure ) . RESULTS In the acupressure group , the overall menstrual symptoms ( 95 % confidence interval [ CI ] = -49.8 to -6.5 , effect size [ ES ] = 0.43 , p = 0.01 ) and two subscales , menstrual pain ( 95 % CI = -16.4 -to -2.2 , ES = 0.45 , p = 0.01 ) and negative affects ( 95 % CI = -11.9 - 2.0 , ES = 0.38 , p = 0.04 ) , revealed that menstrual symptoms decreased significantly after auricular acupressure by the seed-pressure method . The ES for the MDQs were in favor of the auricular acupressure by seed-pressure method . NO level increased in the acupressure group , although this difference did not achieve statistical significance ( p > 0.05 ) . CONCLUSIONS This study supports the effects of auricular acupressure by seed-pressure method in improving menstrual symptoms , and offers a noninvasive complementary therapy for women with primary dysmenorrhea OBJECTIVE We have evaluated the clinical efficacy of yoga for primary dysmenorrhea . Primary dysmenorrhea occurs in 50 % of female adolescents and is a common problem in women of reproductive age . We have assessed whether three yoga poses ( Cobra , Cat , and Fish Poses ) are able to reduce severity and duration of primary dysmenorrhea . METHODS To determine the effectiveness of yoga in adolescents with primary dysmenorrhea , 92 girl students,18 - 22 years old , were r and omly assigned to an experimental group ( n = 50 ) and a control group ( n = 42 ) . The Visual Analog Scale for Pain was used to assess intensity of pain and the pain duration was calculated in terms of hours . Each group was evaluated for three menstrual cycles . At first cycle no method was presented ; the participants only were asked to complete the question naire of menstrual characteristics during their menstrual . Then the participants were asked by the experimental group to do yoga poses at luteal phase , and also to complete the menstrual characteristics question naire in during of menstruation . The control group did not receive any intervention except to complete menstrual characteristics question naire in during of menstruation . RESULTS There was a significant difference in the pain intensity and pain duration in the post-tests compared with the pretest in yoga group ( P < 0.05 ) . The results showed that compared with the Control group , there was a significant difference in the pain intensity and pain duration in the experimental group ( P < 0.05 ) . CONCLUSION Yoga reduced the severity and duration of primary dysmenorrhea . The findings suggest that yoga poses are safe and simple treatment for primary dysmenorrhea BACKGROUND : There are two types of primary dysmenorrhea ( spasmodic and congestive ) which differ from each other in terms of the occurrence time in menstrual cycle , pain quality and other symptoms . The present study aim ed to determine the effect of acupressure at the Sanyinjiao point ( SP-6 ) on severity of menstrual symptoms ( primary outcome ) and the duration of resting time as well as the number of ibuprofen consumption ( secondary outcome ) in the two types of primary dysmenorrhea . METHODS : This was a clustered r and omized controlled trial on 72 eligible students residing in dormitories of public universities of Tabriz , Iran . Determining the type of primary dysmenorrhea using a Menstrual symptoms question naire ( MSQ ) , 36 participants which suffered from each type of dysmenorrhea were enrolled from the four dormitories . The dormitories were r and omly divided into intervention and control groups . No intervention was carried out at the first cycle . During the two next cycles , Sanyinjiao point of the subjects in the intervention group was pressed for twenty minutes at the time of pain . The subjects in both groups were allowed to consume ibuprofen , if needed . During these three cycles , the participants recorded and reported menstrual symptoms severity , duration of resting time and the number of the used ibuprofen . RESULTS : The severity of menstrual symptoms and duration of resting time in the 2nd and 3rd cycles were significantly reduced more than control groups for both spasmodic and congestive types of primary dysmenorrhea . In addition , the aver-age numbers of ibuprofen pills taken by both intervention groups was significantly less than the control groups . There was no significant difference between the two intervention groups in terms of any of the outcomes . CONCLUSIONS : Acupressure is effective on lowering the symptoms of dysmenorrhea and duration of resting time almost equally in both spasmodic and congestive types . Therefore , using this method either alone or along with other methods is recommended to treat dysmenorrhea OBJECTIVES Dysmenorrhea is a common gynecologic disorder . Although non-steroidal anti-inflammatory drugs are commonly used , due to their side effects and lack of response in some individuals , other approaches such as exercise have been considered . This study compared the effect of stretching exercises and mefenamic acid on the reduction of pain and menstruation characteristics in primary dysmenorrhea . METHODS In this r and omized clinical trial , 122 female students with moderate to severe dysmenorrhea were assessed and were placed in either the exercise or mefenamic acid group . The exercise program was performed for 15 minutes , three times a week and included a five-minute warm up and six belly and pelvic stretching exercises for 10 minutes . The mefenamic acid group received 250 mg capsules every eight hours from the onset of menstruation until pain relief . Both interventions were performed during two consecutive menstrual cycles . Pain intensity was measured using a 10 cm visual analog scale . RESULTS The mean pain intensity was significantly higher in the exercise group only in the first cycle ( p = 0.058 ) . In the second cycle , the mean difference in pain reduction in the exercise group was higher than the mefenamic group compared to the start of the study ( p = 0.056 ) and the first cycle ( p = 0.007 ) . There was no significant difference in the severity and duration of pain between the groups ( p > 0.050 ) . CONCLUSIONS Stretching exercises were as effective as mefenamic acid in the treatment of primary dysmenorrhea . Our results suggest that the effect of exercise on relieving menstruation pain increases over time The present study aims at comparing the effects of acupressure using new combination of acupoints , and Ibuprofen on the severity of primary dysmenorrhea ( PD ) . 216 female high school students , aged between 14 to 18 years , were r and omly selected and divided into three groups . Each group underwent different treatment techniques : acupressure , Ibuprofen and sham acupressure as a placebo . The results indicated that the three therapeutic techniques were significantly effective in reducing the pain . However the therapeutic efficacies of acupressure and Ibuprofen were similar with no significant difference , and were significantly better than the placebo . Thus acupressure , with no complications , is recommended as an alternative and also a better choice in the decrease of the severity of PD Background Primary dysmenorrhea is a common and sometimes disabling condition . In recent years , some studies aim ed to improve the treatment of dysmenorrhea , and therefore , introduced several therapeutic measures . This study was design ed to compare the analgesic effect of iron chip containing heat wrap with ibuprofen for the treatment of primary dysmenorrhea . Methods In this r and omized ( I RCT 201107187038N2 ) controlled trial , 147 students ( 18–30 years old ) with the diagnosis of primary dysmenorrhea were enrolled considering the CONSORT guideline . Screening for primary dysmenorrhea was done by a two- question screening tool . The participants were r and omly assigned into one of the intervention groups ( heat Patch and ibuprofen ) . Data regarding the severity and emotional impact of the pain were recorded by a shortened version of McGill Pain Question naire ( SF-MPQ ) . Student 's t test was used for statistical analysis . Results The maximum and minimum pain severities were observed at 2 and 24 hours in both groups . The severity of sensual pain at 8 , 12 , and 24 hours was non-significantly less in the heat Patch group . There was also no significant difference between the groups regarding the emotional impact of pain at the first 2 , 4 , 8 , 12 and 12 hours of menstruation . Conclusions Heat patch containing Iron chip has comparable analgesic effects to ibuprofen and can possibly be used for primary dysmenorrhea . Trial registration I RCT OBJECTIVE To determine if pain relief provided by a wearable heat wrap ( continuous , low-level , topical heat therapy ) is superior to oral acetaminophen for primary dysmenorrhea . STUDY DESIGN A r and omized , active-controlled , multisite , single-blind ( investigator ) , parallel- design study compared an abdominal wrap to an oral medication ( acetaminophen , 1000 mg ) over I day . Pain relief ( 0 - 5 ) and abdominal muscle tightness/cramping ( 0 - 100 ) were recorded at 12 time points . At 24 and 48 hours , menstrual symptom-based quality of life was assessed . RESULTS Three hundred sixty-seven subjects entered the study , with 344 subjects evaluable . The heat wrap was superior to acetaminophen for pain relief over an 8-hour period ( means of 2.48 and 2.17 , p = 0.015 ) and at t hours 3 , 4 , 5 and 6 ( p < or = 0.05 ) . Tightness/cramping was less for the heat wrap versus acetaminophen over 8 hours ( means of 40.4 and 44.5 , p = 0.04 ) and at hours 4 , 5 and 6 ( p < or = 0.05 ) . There was significantly decreased fatigue , fewer mood swings and less lower abdominal cramping ( p < or = 0.05 ) with heat therapy . CONCLUSION Continuous , low-level , topical heat therapy was superior to acetaminophen for the treatment of dysmenorrhea Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES This study aims to evaluate the effects of Sanyinjiao ( SP6 ) acupressure in reducing the pain level and menstrual distress result ing from dysmenorrhea . METHODS Forty participants with dysmenorrhea were assigned to either the acupressure group ( n = 19 ) or the control group ( n = 21 ) . The acupressure group received 20 min of SP6 acupressure during the initial intervention session and was taught to perform the technique for them to do twice a day from the first to third days of their menstrual cycle , 3 months subsequent to the first session . In contrast , the control group was only told to rest . Outcomes were measured through ( 1 ) the Pain Visual Analogue Scale ( PVAS ) , ( 2 ) the Short-Form McGill Pain Question naire ( SF-MPQ ) , and ( 3 ) the Short-Form Menstrual Distress Question naire ( SF-MDQ ) . RESULTS There was a statistically significant decrease in pain score for PVAS ( p = 0.003 ) and SF-MPQ ( p = 0.02 ) immediately after the 20 min of SP6 acupressure . In the self-care periods , significant reduction of PVAS ( p = 0.008 ) , SF-MPQ ( p = 0.012 ) , and SF-MDQ ( p = 0.024 ) scores was noted in the third month of post-intervention . CONCLUSIONS SP6 acupressure has an immediate pain-relieving effect for dysmenorrhea . Moreover , acupressure applied to the SP6 acupoint for 3 consecutive months was effective in relieving both the pain and menstrual distress level result ing from dysmenorrhea Background : Dysmenorrhea is one of the common problems during reproductive ages , with prevalence rate of 60–90 % . This study aim ed to compare the effects of acupressure at Guan yuan ( RN-4 ) and Qu gu ( RN-2 ) acupoints , self-care behaviors training , and ibuprofen on the intensity of primary dysmenorrhea based on McGill pain question naire . Material s and Methods : In the r and omized clinical trial , 120 females , aged between 18 and 25 years , with primary dysmenorrhea , r and omly selected from five dormitories of Shiraz University , Shiraz , Iran were screened and r and omized into acupressure group , in that pressure was applied for 20 min over the 1st 2 days of menstruation for two cycles . In the second group , the training group took part in four educational sessions each lasting for 60–90 min and control group received ibuprofen 400 mg . The intensity of pain before and after the intervention was measured using short-form McGill pain question naire . The data were entered into the SPSS statistical software ( version 16 ) and analyzed using Kruskal – Wallis test , paired t-test , and Chi-square test . Results : A significant difference was found in the mean intensity of pain before and after the intervention in all the three study groups . The mean score of pain intensity was 10.65 ± 5.71 in the training group , 19 ± 5.41 in the control group , and 14.40 ± 6.87 in the acupressure group after the intervention . The results of Kruskal – Wallis test revealed that both interventions were more effective compared to consumption of ibuprofen . Conclusion : Training and acupressure were more effective than ibuprofen in the reduction of dysmenorrhea . Thus , they can be considered as trainable methods without side effects in adolescent girls Background Self-care is a key component of current policies to manage long term conditions . Although most people with long-term health problems care for themselves within lay networks , consultation rates for long-term undifferentiated illness remain high . Promotion of self-care in these individuals requires an underst and ing of their own self-care practice s and needs to be understood in the context of health care pluralism . The aim was to investigate the extent and nature of self-care practice s in patients experiencing long term health problems , sources of information used for self-care , and use of other forms of health care ( conventional health care and complementary and alternative medicine ) . Methods The study involved a cross-sectional community-based survey set in three general practice s in South West Engl and : two in urban areas , one in a rural area . Data were collected using a postal question naire sent to a r and om sample of 3,060 registered adult patients . Respondents were asked to indicate which of six long term health problems they were experiencing , and to complete the question naire in reference to a single ( most bothersome ) problem only . Results Of the 1,347 ( 45 % unadjusted response rate ) who responded , 583 reported having one or more of the six long term health problems and 572 completed the survey question naire . Use of self-care was notably more prevalent than other forms of health care . Nearly all respondents reported using self-care ( mean of four self-care practice s each ) . Predictors of high self-care reported in regression analysis included the reported number of health problems , bothersomeness of the health problem and having received a diagnosis . Although GPs were the most frequently used and trusted source of information , their advice was not associated with greater use of self-care . Conclusions This study reveals both the high level and wide range of self-care practice s undertaken by this population . It also highlights the importance of GPs as a source of trusted information and advice . Our findings suggest that in order to increase self-care without increasing consultation rates , GPs and other health care providers may need more re sources to help them to endorse appropriate self-care practice s and signpost patients to trusted sources of self-care support Background . Primary dysmenorrhea is a common gynaecological condition . Traditional Chinese medicine ( TCM ) acupuncturists commonly treat primary dysmenorrhea and dispense specific self-care advice for this condition . The impact of self-care advice on primary dysmenorrhea is unknown . Methods . 19 TCM acupuncture practitioners from New Zeal and or Australia and 12 New Zeal and women who had recently undergone acupuncture treatment for primary dysmenorrhea as part of a r and omised controlled trial participated in this qualitative , pragmatic study . Focus groups and semistructured interviews were used to collect data . These were recorded , transcribed , and analysed using thematic analysis . Results . The overarching theme was that an acupuncture treatment consisted of “ more than needles ” for both practitioners and participants . Practitioners and participants both discussed the partnership they engaged in during treatment , based on openness and trust . Women felt that the TCM self-care advice was related to positive outcomes for their dysmenorrhea and increased their feelings of control over their menstrual symptoms . Conclusions . Most of the women in this study found improved symptom control and reduced pain . A contributing factor for these improvements may be an increased internal health locus of control and an increase in self-efficacy result ing from the self-care advice given during the clinical trial AIM This paper presents the findings of a study that assessed the effects of acupressure at the Sanyinjiao point on symptoms of primary dysmenorrhoea among adolescent girls . BACKGROUND Dysmenorrhoea is the most common gynaecological disorder among adolescents . Traditional Chinese acupressure derived from acupuncture is a non-invasive technique . Despite renewed interest in the use of acupressure , relatively few studies have been undertaken to examine its effects on primary dysmenorrhoea . METHODS An experimental study was conducted between December 2000 and August 2001 . Participants were female students attending a technical college in Taiwan . None of the 69 participants had a prior history of gynaecological disease or secondary dysmenorrhoea , and all were rated higher than five for pain on a visual analogue scale from 0 to 10 . The experimental group ( n = 35 ) received acupressure at Sanyinjiao ( above the ankle ) while the control group ( n = 34 ) rested for 20 min , while the control group underwent rest in the school health centre for 20 min without receiving acupressure . Fifty participants ( 30 experimental , 20 control ) completed the 4 - 6-week follow-up session . Five instruments were used to collect pretest and post-test data at each session : ( 1 ) Visual Analogue Scale for pain ; ( 2 ) the Short-Form McGill Pain Question naire ; ( 3 ) the Menstrual Distress Question naire ; ( 4 ) the Visual Analogue Scale for anxiety ; and , for the experimental group only , ( 5 ) the Acupressure Self- Assessment Form . Data were analysed using the chi-square test , two- sample t-test and repeated measures two-way anova . RESULTS Acupressure at Sanyinjiao during the initial session reduced the pain and anxiety typical of dysmenorrhoea . In the self-treatment follow-up session , acupressure at Sanyinjiao significantly reduced menstrual pain but not anxiety . Thirty-one ( 87 % ) of the 35 experimental participants reported that acupressure was helpful , and 33 ( 94 % ) were satisfied with acupressure in terms of its providing pain relief and psychological support during dysmenorrhoea . CONCLUSION The findings suggest that acupressure at Sanyinjiao can be an effective , cost-free intervention for reducing pain and anxiety during dysmenorrhoea , and we recommend its use for self-care of primary dysmenorrhoea OBJECTIVE The current study was conducted to evaluate the effect of acupressure on primary dysmenorrhea in Iranian medical sciences students . DESIGN A r and omized controlled pre and post-test design was employed to verify the effects of SP6 acupressure on dysmenorrhea . SETTING A total of 30 young college female students with primary dysmenorrhea were r and omly allocated to intervention ( n = 15 ) and control ( n = 15 ) groups . INTERVENTION The intervention group received SP6 acupressure during menstruation cycle and the control group received light touch on the SP6 acupoint . Using a Visual Analog Scale , the severity of dysmenorrhea was assessed prior to and immediately , 30 min , 1 , 2 , and 3 h following treatment . MAIN OUTCOME MEASURES Data were analyzed using X(2 ) , t-test and ANOVA statistical tests . RESULTS Significant differences were observed in the scores of dysmenorrhea between the two groups immediately after ( 3.50 ± 1.42 vs. 5.06 ± 1.43 , p = 0.004 ) and also 3 h after treatment ( 1.66 ± 1.98 vs. 4.80 ± 1.37 , p = 0.000 ) . CONCLUSIONS Acupressure on the SP6 meridian can be an effective non-invasive nursing intervention for alleviating primary dysmenorrhea and its effects last for 3 h post-treatment STUDY QUESTION Are markers of chronic inflammation associated with menstrual symptom severity and premenstrual syndrome ( PMS ) ? SUMMARY ANSWER Serum levels of inflammatory markers , including interleukin (IL)-2 , IL-4 , IL-10 , IL-12 and interferon (IFN)-γ were positively associated with menstrual symptom severity and /or PMS in young women . WHAT IS KNOWN ALREADY Chronic inflammation has been implicated in the etiology of depression and other disorders that share common features with PMS , but whether inflammation contributes to menstrual symptom severity and PMS is unknown . STUDY DESIGN , SIZE , DURATION Cross-sectional study of 277 women aged 18 - 30 years , conducted in 2006 - 2011 . PARTICIPANTS / MATERIAL S , SETTING , METHODS Participants provided information on menstrual symptoms , lifestyle , diet , anthropometry and other factors by question naire and /or direct measurement , and a mid-luteal phase fasting blood sample was taken between 7 a.m. and 12 p.m. Total , physical and affective menstrual symptom scores were calculated for all participants , of whom 13 % ( n = 37 ) met criteria for moderate-to-severe PMS and 24 % ( n = 67 ) met PMS control criteria . Inflammatory factors assayed in serum included IL-1β , IL-2 , IL-4 , IL-5 , IL-6 , IL-7 , IL-8 , IL-10 , IL-12p70 , IL-13 , tumor necrosis factor-α , granulocyte macrophage colony stimulating factor , IFN-γ and C-reactive protein . MAIN RESULTS AND THE ROLE OF CHANCE After adjustment for age , smoking status and BMI , total menstrual symptom score was positively associated with levels of IL-2 ( percentage difference in women at the 75th percentile of total symptom score versus at the 25th percentile = 24.7 % ; P = 0.04 ) , IL-4 ( 21.5 % ; P = 0.04 ) , IL-10 ( 28.0 % ; P < 0.01 ) and IL-12 ( 42.0 % ; P = 0.02 ) in analyses including all participants . Affective menstrual symptom score was linearly related to levels of IL-2 ( percentage difference at 75th percentile versus 25th percentile = 31.0 % ; P = 0.02 ) , while physical/behavioral symptom score was linearly related to levels of IL-4 ( 19.1 % ; P = 0.03 ) and IL-12 ( 33.2 % ; P = 0.03 ) . Additionally , mean levels of several factors were significantly higher in women meeting PMS criteria compared with women meeting control criteria , including IL-4 ( 92 % higher in cases versus controls ; P = 0.01 ) ; IL-10 ( 87 % ; P = 0.03 ) ; IL-12 ( 170 % ; P = 0.04 ) and IFN-γ ( 158 % ; P = 0.01 ) . LIMITATIONS , REASONS FOR CAUTION Our study has several limitations . While a single blood sample may not perfectly capture long-term levels of inflammation , ample data suggest that levels of cytokines are stable over time . Although we did not base our assessment of PMS on prospect i ve symptom diaries , we used vali date d criteria to define PMS cases and controls , and excluded women with evidence of comorbid mood disorders . Furthermore , because of the cross-sectional design of the study , the temporal relation of inflammatory factors and menstrual symptoms is unclear . WIDER IMPLICATION S OF THE FINDINGS To our knowledge , this is among the first studies to suggest that inflammatory factors may be elevated in women experiencing menstrual symptoms and PMS . Additional studies are needed to determine whether inflammation plays an etiologic role in PMS . STUDY FUNDING /COMPETING INTERESTS This study was funded by the Departments of Public Health and Nutrition and by a Faculty Research Grant , University of Massachusetts Amherst . No conflicts declared . TRIAL REGISTRATION NUMBER The purpose of this study was to identify factors that affect the self-care behaviour of female high school students with dysmenorrhoea . This cross-sectional study utilized a question naire-based survey to underst and the self-care behaviour of female high school students dysmenorrhoeal , along with the factors that affect this behaviour . A cluster r and om sampling method was adopted and question naires were used for data collection . Study participants experienced a moderate level of discomfort from dysmenorrhoea , and perceived dysmenorrhoea as serious . This investigation finds that cues to action raised perceived susceptibility to dysmenorrhoea and the perceived effectiveness of self-care behaviour and , therefore , increased the adoption of self-care behaviour . Hence , school nurses should offer female high school students numerous re sources to apply correct self-care behaviour The purpose of this study was to examine the effects of acupressure on menstrual distress and low back pain ( LBP ) in dysmenorrheic young adult women . In all , 129 female students , who had been experiencing dysmenorrhea with LBP during menstruation and who scored more than 4 points on the visual analog scale for pain , were r and omly assigned to an experimental group and a control group . The experimental group ( n = 65 ) received acupressure massage three times a week for 30 minutes on the sanyinjiao ( SP6 ) , ciliao ( BL32 ) , and taichong ( Liver 3 ) acupoints . The control group ( n = 64 ) received only a manual of menstrual health education without acupressure intervention . Data were collected at five time points : at baseline , 30 minutes , and 4 , 8 , and 12 months after the intervention . During the 12-month follow-up , the experimental group had significantly lower menstrual distress and LBP scores than the control group . Among 65 participants in the experimental group , 53 ( 82 % ) reported a moderate to high levels of menstrual distress , 51 ( 78 % ) reported moderate to high levels of LBP relief , and 49 ( 75 % ) reported moderate to high levels of satisfaction with acupressure . Our findings may serve as a reference for health care professionals and young women to improve self-care during menstruation and help further underst and the therapeutic effects of acupressure on menstrual distress and LBP Objective To compare the efficacy of topically applied heat for menstrual pain with oral ibuprofen and placebo treatment . Methods We conducted a r and omized placebo and active controlled ( double dummy ) , parallel study using an abdominal patch ( heated or unheated ) for approximately 12 consecutive hours per day and oral medication ( placebo or ibuprofen 400 mg ) three times daily , approximately 6 hours apart for 2 consecutive days . Pain relief and pain intensity were recorded at 17 time points . There was at least 85 % power to detect a true one-unit difference in the 2-day pain relief treatment means for comparisons with the unheated patch plus oral placebo group using a one-tailed test at the .05 level of significance , based on an observed within-group st and ard deviation of 1.147 . Results Eighty-four patients were enrolled and 81 completed the study protocol . Over the 2 days of treatment , the heated patch plus placebo tablet group ( mean 3.27 , P < .001 ) , the unheated patch plus ibuprofen group ( mean 3.07 , P = .001 ) , and the combination heated patch plus ibuprofen group ( mean 3.55 , P < .001 ) had significantly greater pain relief than the unheated patch plus placebo group ( mean 1.95 ) . Greater pain relief was not observed for the combination heated patch plus ibuprofen group compared with the unheated patch plus ibuprofen group ( P = .096 ) ; however , the time to noticeable pain relief was statistically significantly shorter for the heated patch plus ibuprofen group ( median 1.5 hours ) compared with the unheated patch plus ibuprofen group ( median 2.79 hours , P = .01 ) . Conclusion Continuous low-level topical heat therapy was as effective as ibuprofen for the treatment of dysmenorrhea Using prospect i ve daily reporting , this study examined the relationship between exercise participation and menstrual pain , physical symptoms , and negative mood . Twenty-one sedentary women and 20 women who participated in regular exercise completed a modified version of the Prospect i ve Record of the Impact and Severity of Menstrual Symptoms ( PRISM ) calendar for two complete menstrual cycles . Analyses revealed that pain was greater in all women during menses compared to the follicular and luteal phases . Moreover , exercise status was found to interact with menstrual cycle phase in predicting pain . Specifically , exercise participants reported less pain than sedentary women during menses , though there were no differences between the two groups during the follicular and luteal phases . Exercise status was also associated with greater reports of anxiety during menses . Otherwise , exercise status was not observed to influence reports of symptoms or negative mood throughout the menstrual cycle . These results suggest that participation in even moderate amounts of exercise affects the experience of menstrual pain in women OBJECTIVE The aim of this study was to describe the prevalence , clinical effect , characteristics , and underlying risk factors of primary dysmenorrhea ( PD ) in Canada . METHODS A stratified , r and om sample of 2721 women 18 years and older was identified , and the women were interviewed by telephone . Data about menstrual symptoms and patterns and socio-demographic factors were obtained . The frequency , severity , and effect of menstrual pain were quantified . Logistic regression analysis was performed in order to identify independent risk factors for PD . RESULTS In the sample , 1546 women were having menstrual periods ; of these , 934 ( 60 % ) met the criteria for PD . Sixty percent of the women with PD described their pain as moderate or severe . Fifty-one percent reported that their activities had been limited , and 17 % reported missing school or work because of PD . The prevalence of PD decreased with increasing age ( P < 0.001 ) and increased with smoking ( P = 0.002 ) . Users of oral contraceptives ( OCs ) tended to have less pain than non-users ( P = 0.005 ) . Socio-economic status , nulliparity , and earlier age at menarche were not independently associated with PD . However , nulliparous women , smokers , and women not using OCs were more likely to report disabling symptoms . CONCLUSIONS The majority of Canadian women will suffer from dysmenorrhea at some time during their reproductive years . Available prescription treatments are underused . Young age , smoking , and non-use of OCs are independent risk factors for PD The prevalence of dysmenorrhea was studied in a r and om sample of 19-year-old women from an urban Swedish population . Dysmenorrhea was reported by 72 % of the women . Fifteen percent suffered from dysmenorrhea which limited daily activity and was unimproved by analgesics . Dysmenorrhea occurred significantly ( p less than 0.01 ) more often in women not using oral contraceptives . A significant correlation ( p less than 0.01 ) was found between early menarche and an increased severity of dysmenorrhea . There was a significant correlation ( p less than 0.01 ) between the severity of dysmenorrhea and the amount of menstrual flow . Parous women had significantly ( p less than 0.01 ) less dysmenorrhea than women who had never been pregnant or women who had experienced a legal or spontaneous abortion . Smokers as compared to nonsmokers had significantly ( p less than 0.01 ) less dysmenorrhea . The severity of dysmenorrhea was not affected by height , weight , or regularity of the menstrual cycle . Absenteeism as a result of dysmenorrhea was evaluated OBJECTIVE To examine whether applying a simple acupressure protocol to the Taichong point is effective in relieving dysmenorrhea . METHODS In this single-blind trial 194 students with dysmenorrhea were r and omized to receive acupressure 5 days before menstruation for 3 months on either the Taichong or a placebo point . The severity of dysmenorrhea was assessed in the first and last of the 4 study cycles using the And ersch and Milsom scale . The χ(2 ) test , t test , Mann-Whitney U test , and Wilcoxon signed rank test were used for data analysis . RESULTS The difference in dysmenorrhea severity between the 2 groups was not significant in the first cycle but it was significant in the fourth cycle ( U = 2377.00 , P<0.001 ) , and the decrease in dysmenorrhea severity was also significant in the study group ( P<0.05 ) . CONCLUSION Applying a simple pressure protocol to the Taichong acupoint was an effective and inexpensive way of decreasing the severity of dysmenorrhea AIM AND OBJECTIVES To examine a comparison between Hegu and Sanyinjiao matched points and Hegu , Zusanli single point on adolescent girls ' menstrual distress , pain and anxiety perception . BACKGROUND Primary dysmenorrhoea is a major cause of temporary disability , with a prevalence ranging from 60 - 93 % , depending upon the population and study . No one has yet compared the effects of single point and multiple point acupressures . Design . A single blind r and omised experimental study was used . METHODS Adolescents ( n = 134 ) r and omly assigned to experimental groups Zusanli ( n = 30 ) , Hegu ( n = 33 ) and Hegu-Sanyinjiao Matched Points ( n = 36 ) received acupressure intervention protocol for 20 minutes , while the control group ( n = 35 ) did not receive any acupressure intervention . Four instruments were used to collect data : ( 1 ) the Visual Analog Scale for Pain ; ( 2 ) the Menstrual Distress Question naire Short Form ; ( 3 ) the Short-Form McGill Pain Question naire and ( 4 ) the Visual Analog Scale for Anxiety . RESULTS During the six-month follow-up , acupressure at matched points Hegu and Sanyinjiao reduced the pain , distress and anxiety typical of dysmenorrhoea . Acupressure at single point Hegu was found , effectively , to reduce menstrual pain during the follow-up period , but no significant difference for reducing menstrual distress and anxiety perception was found . Zusanli acupressure had no significant effects of reducing menstrual pain , distress and anxiety perception . CONCLUSION This controlled trial provides preliminary evidence that six-month acupressure therapy provides female adolescents with dysmenorrhoea benefits . RELEVANCE TO CLINICAL PRACTICE Acupressure is an effective and safe non-pharmacologic strategy for the treatment of primary dysmenorrhoea . We recommend the use of acupressure for self-care of primary dysmenorrhoea at Hegu and Sanyinjiao matched points and single point Hegu , as pressure placement at these points is easy for adolescent girls to learn and practice OBJECTIVES To investigate the effects of a yoga program on menstrual cramps and menstrual distress in undergraduate students with primary dysmenorrhea . DESIGN Single-blind , r and omized controlled trial . PARTICIPANTS 40 r and omly selected undergraduate nursing students , with 20 each assigned to an exercise or a control group . INTERVENTION The participants engaged in a yoga program for 60 minutes once a week for 12 weeks . The program consisted of physical exercise combined with relaxation and meditation . OUTCOME MEASURES Menstrual cramps and menstrual distress levels were measured by using the Visual Analogue Scale for Pain and the Menstrual Distress Question naire , respectively . Data were analyzed by using the Kolmogorov-Smirnov and Shapiro-Wilk normality tests , t-test , chi-square test , logistic regression analysis , and multivariate analysis of variance ( SPSS program ) . RESULTS Menstrual pain intensity ( group difference , -0.94 ; 95 % confidence interval [ CI ] , -1.47 to -0.42 ; p = 0.001 ) and menstrual distress ( group difference , -1.13 ; 95 % CI , -1.43 to -0.82 ; p < 0.0001 ) scores decreased significantly in the experimental group compared with the control group . CONCLUSIONS These findings indicate that yoga interventions may reduce menstrual cramps and menstrual distress in female undergraduate students with primary dysmenorrhea |
1,633 | 31,660,038 | CONCLUSION Allicin as an add-on therapy improves H. pylori eradication , healing of ulcers , and remission of symptoms . | BACKGROUND Allicin ( 2-propene-1-sulfinothioic acid S-2-propenyl ester , diallyl thiosulfinate ) extracted from garlic , has proven activity against Helicobacter pylori ( H. Pylori ) infection .
In recent years , clinical trials have explored its utility as an add-on therapy with variable outcomes reported .
AIM To perform a systemic review of allicin as an add-on treatment for H. Pylori infection and assess its efficacy in r and omized controlled trials ( RCTs ) . | Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective : There have been a number of reports that natural foods such as garlic , honey , and capsaicin can inhibit Helicobacter pylori in vitro and each report has suggested the natural ingredient be used for treatment of the infection . We investigated whether garlic or capsaicin-containing peppers would actually inhibit H. pylori in vivo . Methods : We performed a prospect i ve crossover study in healthy H. pylori-infected adults . We used the urea breath test to assess the status of the H. pylori infection . On separate days subjects received three test meals consisting of beef , tortillas , and salad with one of the following : fresh garlic ( 10 sliced cloves ) , capsaicin ( six sliced fresh jalapeños ) , two tablets of bismuth subsalicylate ( Pepto-Bismol , positive control ) , or nothing added ( negative control ) . Breath testing was done before the first meal , the evening meal , and the following morning . At least 2 days elapsed between the test substances . Results : Twelve subjects participated ( seven men , five women ) , with an average age of 41.4 yr , range 27–51 yr . Ten subjects received garlic , six received jalapeños , and 11 received bismuth . Neither garlic nor capsaicin had any in vivo effect on H. pylori ( median urease activity 28.5 vs 39.8 and 43.7 vs 46.6 before and after garlic and jalapeños , respectively ) p > 0.8 . Bismuth had a marked inhibitory effect ( median 55.8 vs 14.3 before and after bismuth ) p < 0.001 , respectively . Conclusions : This study did not support a role for either garlic or jalapeños in the treatment of H. pylori infection . Caution must be used when attempting to extrapolate data from in vitro studies to the in vivo condition In this study , in vivo effectiveness of ascorbic acid ( AA ) , beta carotene ( BC ) and allicin in HP eradication were evaluated . 210 patients who are HP positive in biopsy were involved in this study . The patients r and omised to seven treatment groups ( each group consisting of 30 patients ) . The first group was given st and ard eradication treatment ( lansaprasol 30 mg bid , clarithromycin 500 mg bid , amoxicillin 1 g bid for 14 days ) . Second group received AA 1000 mg/day in addition to the st and ard treatment . Third group received only AA 1000 mg/day for 14 days . Fourth group was treated with st and ard regiment plus 120 mg/day BC . Fifth group was given only BC 120 mg/day for 14 days . Sixth group was given st and ard regiment and allicin 4200 micrograms/day . Seventh group received only Allicin 1200 micrograms/day for 14 days . The eradication was achieved in 20 ( 66.6 % ) in group I , 15 ( 50 % ) in group II , 3 ( 10 % ) in group III , 15 ( 50 % ) in group IV , 0 ( 0 % ) in group V , 27 ( 90 % ) in group VI and 7 ( 23.3 % ) in group VII . Allicin seemed to be potentially effective agent for HP eradication but ascorbic acid , beta caroten was found to be ineffective Resistance of Helicobacter pylori to clarithromycin and metronidazole is now found worldwide . Steam‐distilled garlic oil has in vitro activity against H. pylori and may be a useful alternative treatment strategy OBJECTIVE To characterize Helicobacter pylori isolates from western Argentina using virulence markers and antimicrobial susceptibility patterns in order to assess the association between virulent genotypes , antimicrobial resistance , and disease . DNA fingerprinting was also evaluated for the segregation of virulent or resistant strain clusters . METHODS Genotyping of 299 H. pylori isolates was performed by PCR using specific primers for the cagA , vacA and iceA genes . R and om amplification of polymorphic DNA (RAPD)-PCR and rep-PCR genetic clustering were assessed using five r and om primers and BOXA1R and ERIC primers , respectively . Resistance to clarithromycin ( Cla ) and metronidazole ( Mtz ) was assessed by the agar dilution method . RESULTS It was observed that 40.8 % of the genotypes were cagA-positive ; 66.9 % were vacA s1m1 genotype and the iceA1 allele was found in 40.8 % . A significant correlation ( p=0.0000 ) was observed between cagA positivity and vacA s1m1/iceA1 genotypes . Triple virulent genotypes were statistically associated with peptic ulcer ( PU ) ( p=0.0001 ) and Cla resistance ( p=0.0000 ) . RAPD fingerprints obtained with AO2 primers identified clusters that were strongly associated with PU , virulence markers , and resistance to Cla and Mtz . CONCLUSIONS The H. pylori isolates that harbored two or three virulence markers were more resistant to Cla and Mtz . Combined analysis of virulent genotypes and resistance patterns may permit identification of high-risk patients to prevent PU later in life or to avoid antimicrobial treatment failure Background : Due to increasing antimicrobial resistance , a bismuth-based quadruple regimen has been recommended as an alternative first-line therapy for Helicobacter pylori ( H pylori ) eradication . However , different results are varied greatly and the availability of bismuth was limited in some countries . We assessed the efficacy and safety of 14-day berberine-containing quadruple therapy as an alternative regimen for H pylori eradication . Methods : In a r and omized , open-label , non-inferiority , phase IV trial between November 25 , 2014 , and October 15 , 2015 , 612 treatment-naive patients were r and omly assigned to 14-day berberine-containing ( n = 308 ) or 14-day bismuth-containing ( n = 304 ) quadruple therapy . The primary outcomes were eradication rates determined by the 13C urea breath test ( 13C-UBT ) 28 days after the end of treatment . The secondary outcomes were adverse events and compliance . Results : The baseline demographic data including age , gender , body mass index ( BMI ) , general condition and severity score were not statistically different in both groups . The eradication rates in bismuth and berberine groups were 86.4 % ( 266/308 ) and 90.1 % ( 274/304 ) in intention-to-treat ( ITT ) analysis ( P = .149 ) , and 89.6 % ( 266/297 ) and 91.3 % ( 273/299 ) in per- protocol ( PP ) analysis ( P = .470 ) , respectively . No statistically significant difference was found in the overall incidence of adverse events between both groups ( 35.7 % vs 28.6 % , P = .060 ) . Conclusions : Both regimens achieved the recommended efficacy for H pylori eradication . The berberine-containing quadruple regimen was not inferior to bismuth-containing quadruple regimen and can be recommended as an alternative regimen for H pylori eradication in the local region Purpose The present study was done to assess the prevalence rate , antibiotic resistance pattern and genotyping status of the Helicobacter pylori strains isolated from human and animal gastric biopsy sample s. Patients and methods A total of 1,150 gastric biopsy sample s were r and omly collected from humans ( children and adults ) and animals ( cows , sheep and goats ) . All sample s were subjected to culture , urease test and histopathologic examination . H. pylori isolates were also confirmed using the 16S rRNA gene PCR-amplification . Antibiotic resistance pattern was assessed by the disk diffusion method . Distribution of different genotypes was studied by PCR . Results The prevalence of H. pylori in gastric biopsy sample s which were studied using urease test , culture and histological examination were 57.04 % , 55.40 % and 60.80 % , respectively . Sample s that were collected from adult humans ( 78 % ) and sheep ( 70 % ) had the highest prevalence of H. pylori strains , while those of goats ( 0.6 % ) and cows ( 4 % ) had the lowest . Findings of the culture method were confirmed using PCR-based amplification of 16S rRNA . Distribution of H. pylori among the gastric ulcers , duodenal ulcers , chronic gastritis gastric cancer and chronic cancer sample s were 10.40 % , 15.70 % , 96.50 % , 0.60 % and 3.14 % , respectively . H. pylori strains harbored the highest prevalence of resistance against ampicillin ( 74.4 % ) , clarithromycin ( 63.4 % ) , trimethoprim ( 61.5 % ) and metronidazole ( 61.5 % ) . The most commonly detected genotypes among the H. pylori strains isolated from different types of biopsy sample s were cagA ( 84.79 % ) , vacA m2 ( 55.95 % ) , vacA s1a ( 49.84 % ) , cagE ( 48.58 % ) , iceA1 ( 47.02 % ) and iceA2 ( 47.02 % ) . Conclusion High prevalence of antibiotic resistance and virulent genotypes indicates an important public health issue . Similarities in antibiotic resistance and genotyping pattern of H. pylori strains isolated from humans and animals may show their similar routes of infection |
1,634 | 27,633,105 | Based on the findings and the limitations in study design , we conclude that adherence to the MD is associated with better cognitive performance .
However , it should be noted that the majority of findings come from epidemiologic studies that provide evidence for a correlation between the MD and cognition but not for a cause- and -effect relation . | A growing body of evidence suggests that adherence to the Mediterranean diet ( MD ) may protect against cognitive decline and dementia .
Many epidemiologic studies and several r and omized controlled trials ( RCTs ) have found positive effects of the MD on cognitive function , but findings remain inconsistent .
The aim of this systematic review was to provide an up date on the current knowledge of the effects of the MD on cognitive function , cognitive impairment , Alzheimer disease ( AD ) , and all-type dementia . | CONTEXT Laboratory findings have suggested that oxidative stress may contribute to the pathogenesis of Alzheimer disease . Therefore , the risk of Alzheimer disease might be reduced by intake of antioxidants that counteract the detrimental effects of oxidative stress . OBJECTIVE To determine whether dietary intake of antioxidants is related to risk of Alzheimer disease . DESIGN AND SETTING The Rotterdam Study , a population -based , prospect i ve cohort study conducted in the Netherl and s. PARTICIPANTS A total of 5395 participants who , at baseline ( 1990 - 1993 ) , were aged at least 55 years , free of dementia , and noninstitutionalized and had reliable dietary assessment . Participants were reexamined in 1993 - 1994 and 1997 - 1999 and were continuously monitored for incident dementia . MAIN OUTCOME MEASURES Incidence of Alzheimer disease , based on Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition ( DSM-III-R ) criteria and National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer Disease and Related Disorders Association ( NINCDS-ADRDA ) criteria , associated with dietary intake of beta carotene , flavonoids , vitamin C , and vitamin E. RESULTS After a mean follow-up of 6 years , 197 participants developed dementia , of whom 146 had Alzheimer disease . When adjustments were made for age , sex , baseline Mini-Mental State Examination score , alcohol intake , education , smoking habits , pack-years of smoking , body mass index , total energy intake , presence of carotid plaques , and use of antioxidative supplements , high intake of vitamin C and vitamin E was associated with lower risk of Alzheimer disease ( rate ratios [ RRs ] per 1-SD increase in intake were 0.82 [ 95 % confidence interval [ CI ] , 0.68 - 0.99 ] and 0.82 [ 95 % CI , 0.66 - 1.00 ] , respectively ) . Among current smokers , this relationship was most pronounced ( RRs , 0.65 [ 95 % CI , 0.37 - 1.14 ] and 0.58 [ 95 % CI , 0.30 - 1.12 ] , respectively ) and also was present for intake of beta carotene ( RR , 0.49 [ 95 % CI , 0.27 - 0.92 ] ) and flavonoids ( RR , 0.54 [ 95 % CI , 0.31 - 0.96 ] ) . The associations did not vary by education or apolipoprotein E genotype . CONCLUSION High dietary intake of vitamin C and vitamin E may lower the risk of Alzheimer disease Abstract The traditional Mediterranean diet ( MedDiet ) has shown beneficial effects on cognitive decline . Nevertheless , diet – gene interactions have been poorly evaluated . We aim ed to investigate diet – gene interaction in the PREDIMED-NAVARRA r and omized trial . A total of 522 participants ( 67 ± 6 years at baseline ) enrolled in the PREDIMED-NAVARRA trial were r and omly allocated to one of three diets : two MedDiets ( supplemented with either extra-virgin olive oil or nuts ) or a low-fat diet . They were evaluated with the Mini-Mental State Examination ( MMSE ) and the Clock Drawing Test ( CDT ) after 6.5 years of intervention . Subjects were genotyped for CR1-rs3818361 , CLU-rs11136000 , PICALM-rs3851179 and Apolipoprotein E ( ApoE ) genes . We studied MedDiet – gene interactions for cognition and assessed the effect of the MedDiet on cognition across different genetic profiles . A significant interaction ( p = 0.041 ) between CLU-rs11136000 and the MedDiet intervention on the MMSE was found with a beneficial effect of MedDiet among carriers of the T minor allele ( B = 0.97 , 95 % CI 0.45–1.49 ) . Similar effect was observed for CR1-rs3818361 , but no significant interaction was observed ( p = 0.335 ) . For PICALM-rs3851179 , the MedDiet intervention showed a beneficial effect in both genotype groups . No apparent interaction was found for the CDT between intervention and gene variants . Similarly , participants r and omly allocated to MedDiet groups , with favorable profiles of CR1 , CLU and PICALM genes , significantly improved CDT scores compared to controls with the same genetic profile . Cognitive performance was better for non-ApoE4 and for ApoE4 carriers of MedDiet groups compared to controls , but for CDT performance , we only found statistical significant differences for non-ApoE4 carriers . A MedDiet intervention modulates the effect of genetic factors on cognition . The effect of MedDiet might be greater for subjects with a more favorable genetic profile BACKGROUND Adherence to a Mediterranean diet may improve longevity , but relevant data are limited . METHODS We conducted a population -based , prospect i ve investigation involving 22,043 adults in Greece who completed an extensive , vali date d , food-frequency question naire at base line . Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet ( range of scores , 0 to 9 , with higher scores indicating greater adherence ) . We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality , as well as mortality due to coronary heart disease and mortality due to cancer , with adjustment for age , sex , body-mass index , physical-activity level , and other potential confounders . RESULTS During a median of 44 months of follow-up , there were 275 deaths . A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality ( adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score , 0.75 [ 95 percent confidence interval , 0.64 to 0.87 ] ) . An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease ( adjusted hazard ratio , 0.67 [ 95 percent confidence interval , 0.47 to 0.94 ] ) and death due to cancer ( adjusted hazard ratio , 0.76 [ 95 percent confidence interval , 0.59 to 0.98 ] ) . Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant . CONCLUSIONS Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality CONTEXT Higher adherence to a Mediterranean-type diet is linked to lower risk for mortality and chronic diseases , but its association with cognitive decline is unclear . OBJECTIVE To investigate the association of a Mediterranean diet with change in cognitive performance and risk for dementia in elderly French persons . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 1410 adults ( > or = 65 years ) from Bordeaux , France , included in the Three-City cohort in 2001 - 2002 and reexamined at least once over 5 years . Adherence to a Mediterranean diet ( scored as 0 to 9 ) was computed from a food frequency question naire and 24-hour recall . MAIN OUTCOME MEASURES Cognitive performance was assessed on 4 neuropsychological tests : the Mini-Mental State Examination ( MMSE ) , Isaacs Set Test ( IST ) , Benton Visual Retention Test ( BVRT ) , and Free and Cued Selective Reminding Test ( FCSRT ) . Incident cases of dementia ( n = 99 ) were vali date d by an independent expert committee of neurologists . RESULTS Adjusting for age , sex , education , marital status , energy intake , physical activity , depressive symptomatology , taking 5 medications/d or more , apolipoprotein E genotype , cardiovascular risk factors , and stroke , higher Mediterranean diet score was associated with fewer MMSE errors ( beta = -0.006 ; 95 % confidence interval [ CI ] , -0.01 to -0.0003 ; P = .04 for 1 point of the Mediterranean diet score ) . Performance on the IST , BVRT , or FCSRT over time was not significantly associated with Mediterranean diet adherence . Greater adherence as a categorical variable ( score 6 - 9 ) was not significantly associated with fewer MMSE errors and better FCSRT scores in the entire cohort , but among individuals who remained free from dementia over 5 years , the association for the highest compared with the lowest group was significant ( adjusted for all factors , for MMSE : beta = -0.03 ; 95 % CI , -0.05 to -0.001 ; P = .04 ; for FCSRT : beta = 0.21 ; 95 % CI , 0.008 to 0.41 ; P = .04 ) . Mediterranean diet adherence was not associated with the risk for incident dementia ( fully adjusted model : hazard ratio , 1.12 ; 95 % CI , 0.60 to 2.10 ; P = .72 ) , although power to detect a difference was limited . CONCLUSIONS Higher adherence to a Mediterranean diet was associated with slower MMSE cognitive decline but not consistently with other cognitive tests . Higher adherence was not associated with risk for incident dementia IMPORTANCE Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline , a strong risk factor for development of dementia . Epidemiologic studies suggest that a Mediterranean diet , an antioxidant-rich cardioprotective dietary pattern , delays cognitive decline , but clinical trial evidence is lacking . OBJECTIVE To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet . DESIGN , SETTING , AND PARTICIPANTS Parallel-group r and omized clinical trial of 447 cognitively healthy volunteers from Barcelona , Spain ( 233 women [ 52.1 % ] ; mean age , 66.9 years ) , at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1 , 2003 , through December 31 , 2009 . All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study . INTERVENTIONS Participants were r and omly assigned to a Mediterranean diet supplemented with extravirgin olive oil ( 1 L/wk ) , a Mediterranean diet supplemented with mixed nuts ( 30 g/d ) , or a control diet ( advice to reduce dietary fat ) . MAIN OUTCOMES AND MEASURES Rates of cognitive change over time based on a neuropsychological test battery : Mini-Mental State Examination , Rey Auditory Verbal Learning Test ( RAVLT ) , Animals Semantic Fluency , Digit Span subtest from the Wechsler Adult Intelligence Scale , Verbal Paired Associates from the Wechsler Memory Scale , and the Color Trail Test . We used mean z scores of change in each test to construct 3 cognitive composites : memory , frontal ( attention and executive function ) , and global . RESULTS Follow-up cognitive tests were available in 334 participants after intervention ( median , 4.1 years ) . In multivariate analyses adjusted for confounders , participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT ( P = .049 ) and Color Trail Test part 2 ( P = .04 ) compared with controls ; no between-group differences were observed for the other cognitive tests . Similarly adjusted cognitive composites ( mean z scores with 95 % CIs ) for changes above baseline of the memory composite were 0.04 ( -0.09 to 0.18 ) for the Mediterranean diet plus olive oil , 0.09 ( -0.05 to 0.23 ; P = .04 vs controls ) for the Mediterranean diet plus nuts , and -0.17 ( -0.32 to -0.01 ) for the control diet . Respective changes from baseline of the frontal cognition composite were 0.23 ( 0.03 to 0.43 ; P = .003 vs controls ) , 0.03 ( -0.25 to 0.31 ) , and -0.33 ( -0.57 to -0.09 ) . Changes from baseline of the global cognition composite were 0.05 ( -0.11 to 0.21 ; P = .005 vs controls ) for the Mediterranean diet plus olive oil , -0.05 ( -0.27 to 0.18 ) for the Mediterranean diet plus nuts , and -0.38 ( -0.57 to -0.18 ) for the control diet . All cognitive composites significantly ( P < .05 ) decreased from baseline in controls . CONCLUSIONS AND RELEVANCE In an older population , a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N35739639 CONTEXT Both higher adherence to a Mediterranean-type diet and more physical activity have been independently associated with lower Alzheimer disease ( AD ) risk but their combined association has not been investigated . OBJECTIVE To investigate the combined association of diet and physical activity with AD risk . DESIGN , SETTING , AND PATIENTS Prospect i ve cohort study of 2 cohorts comprising 1880 community-dwelling elders without dementia living in New York , New York , with both diet and physical activity information available . St and ardized neurological and neuropsychological measures were administered approximately every 1.5 years from 1992 through 2006 . Adherence to a Mediterranean-type diet ( scale of 0 - 9 ; trichotomized into low , middle , or high ; and dichotomized into low or high ) and physical activity ( sum of weekly participation in various physical activities , weighted by the type of physical activity [ light , moderate , vigorous ] ; trichotomized into no physical activity , some , or much ; and dichotomized into low or high ) , separately and combined , were the main predictors in Cox models . Models were adjusted for cohort , age , sex , ethnicity , education , apolipoprotein E genotype , caloric intake , body mass index , smoking status , depression , leisure activities , a comorbidity index , and baseline Clinical Dementia Rating score . MAIN OUTCOME MEASURE Time to incident AD . RESULTS A total of 282 incident AD cases occurred during a mean ( SD ) of 5.4 ( 3.3 ) years of follow-up . When considered simultaneously , both Mediterranean-type diet adherence ( compared with low diet score , hazard ratio [ HR ] for middle diet score was 0.98 [ 95 % confidence interval { CI } , 0.72 - 1.33 ] ; the HR for high diet score was 0.60 [ 95 % CI , 0.42 - 0.87 ] ; P = .008 for trend ) and physical activity ( compared with no physical activity , the HR for some physical activity was 0.75 [ 95 % CI , 0.54 - 1.04 ] ; the HR for much physical activity was 0.67 [ 95 % CI , 0.47 - 0.95 ] ; P = .03 for trend ) were associated with lower AD risk . Compared with individuals neither adhering to the diet nor participating in physical activity ( low diet score and no physical activity ; absolute AD risk of 19 % ) , those both adhering to the diet and participating in physical activity ( high diet score and high physical activity ) had a lower risk of AD ( absolute risk , 12 % ; HR , 0.65 [ 95 % CI , 0.44 - 0.96 ] ; P = .03 for trend ) . CONCLUSION In this study , both higher Mediterranean-type diet adherence and higher physical activity were independently associated with reduced risk for AD To examine the association between dietary habits , cognitive functioning and brain volumes in older individuals , data from 194 cognitively healthy individuals who participated in the Prospect i ve Investigation of the Vasculature in Uppsala Seniors cohort were used . At age 70 , participants kept diaries of their food intake for 1week . These records were used to calculate a Mediterranean diet ( MeDi ) score ( comprising dietary habits traditionally found in Mediterranean countries , e.g. high intake of fruits and low intake of meat ) , with higher scores indicating more pronounced MeDi-like dietary habits . Five years later , participants ' cognitive capabilities were examined by the seven minute screening ( 7MS ) ( a cognitive test battery used by clinicians to screen for dementia ) , and their brain volumes were measured by volumetric magnetic resonance imaging . Multivariate linear regression analyses were constructed to examine the association between the total MeDi score and cognitive functioning and brain volumes . In addition , possible associations between MeDi 's eight dietary features and cognitive functioning and brain volumes were investigated . From the eight dietary features included in the MeDi score , pertaining to a low consumption of meat and meat products was linked to a better performance on the 7MS test ( P=0.001 ) and greater total brain volume ( i.e. the sum of white and gray matter , P=0.03 ) when controlling for potential confounders ( e.g. BMI ) in the analysis . Integrating all dietary features into the total MeDi score explained less variance in cognitive functioning and brain volumes than its single dietary component meat intake . These observational findings suggest that keeping to a low meat intake could prove to be an impact-driven public health policy to support healthy cognitive aging , when confirmed by longitudinal studies . Further , they suggest that the MeDi score is a construct that may mask possible associations of single MeDi features with brain health domains in elderly population Background : We previously reported that the Mediterranean diet ( MeDi ) is related to lower risk for Alzheimer disease ( AD ) . Whether MeDi is associated with subsequent AD course and outcomes has not been investigated . Objectives : To examine the association between MeDi and mortality in patients with AD . Methods : A total of 192 community-based individuals in New York who were diagnosed with AD were prospect ively followed every 1.5 years . Adherence to the MeDi ( 0- to 9-point scale with higher scores indicating higher adherence ) was the main predictor of mortality in Cox models that were adjusted for period of recruitment , age , gender , ethnicity , education , APOE genotype , caloric intake , smoking , and body mass index . Results : Eighty-five patients with AD ( 44 % ) died during the course of 4.4 ( ±3.6 , 0.2 to 13.6 ) years of follow-up . In unadjusted models , higher adherence to MeDi was associated with lower mortality risk ( for each additional MeDi point hazard ratio 0.79 ; 95 % CI 0.69 to 0.91 ; p = 0.001 ) . This result remained significant after controlling for all covariates ( 0.76 ; 0.65 to 0.89 ; p = 0.001 ) . In adjusted models , as compared with AD patients at the lowest MeDi adherence tertile , those at the middle tertile had lower mortality risk ( 0.65 ; 0.38 to 1.09 ; 1.33 years ' longer survival ) , whereas subjects at the highest tertile had an even lower risk ( 0.27 ; 0.10 to 0.69 ; 3.91 years ' longer survival ; p for trend = 0.003 ) . Conclusion : Adherence to the Mediterranean diet ( MeDi ) may affect not only risk for Alzheimer disease ( AD ) but also subsequent disease course : Higher adherence to the MeDi is associated with lower mortality in AD . The gradual reduction in mortality risk for higher MeDi adherence tertiles suggests a possible dose-response effect Abstract Objective To evaluate any association between obesity in middle age , measured by body mass index and skinfold thickness , and risk of dementia later in life . Design Analysis of prospect i ve data from a multiethnic population based cohort . Setting Kaiser Permanente Northern California Medical Group , a healthcare delivery organisation . Participants 10 276 men and women who underwent detailed health evaluations from 1964 to 1973 when they were aged 40 - 45 and who were still members of the health plan in 1994 . Main outcome measures Diagnosis of dementia from January 1994 to April 2003 . Time to diagnosis was analysed with Cox proportional hazard models adjusted for age , sex , race , education , smoking , alcohol use , marital status , diabetes , hypertension , hyperlipidaemia , stroke , and ischaemic heart disease . Results Dementia was diagnosed in 713 ( 6.9 % ) participants . Obese people ( body mass index ≥ 30 ) had a 74 % increased risk of dementia ( hazard ratio 1.74 , 95 % confidence interval 1.34 to 2.26 ) , while overweight people ( body mass index 25.0 - 29.9 ) had a 35 % greater risk of dementia ( 1.35 , 1.14 to 1.60 ) compared with those of normal weight ( body mass index 18.6 - 24.9 ) . Compared with those in the lowest fifth , men and women in the highest fifth of the distribution of subscapular or tricep skinfold thickness had a 72 % and 59 % greater risk of dementia , respectively ( 1.72 , 1.36 to 2.18 , and 1.59 , 1.24 to 2.04 ) . Conclusions Obesity in middle age increases the risk of future dementia independently of comorbid conditions PURPOSE Epidemiological studies have suggested that cholesterol lowering could affect psychological functioning . This study was design ed to test whether cholesterol-lowering diets adversely affect mood and cognitive function.5.2 mM [ 198 mg/dL ] ) to either a low-fat diet , a Mediterranean diet , or a waiting-list control . Cholesterol levels , psychological well-being ( depression , anxiety , hostility ) , and cognitive function were assessed at baseline , 6 weeks , and 12 weeks . RESULTS Total serum cholesterol levels fell significantly more in the intervention groups ( 8.2 % reduction ) than in the control group ( P < 0.001 ) . All three groups showed a modest improvement in psychological well-being during the 12-week treatment period , but there were no differences among the groups . There were no between-group differences on three measures of cognitive function , but for a fourth measure , which involved the task with the greatest processing load , the two intervention groups did significantly worse ( P < 0.001 ) than the control group . The change in performance was correlated with the change in total serum cholesterol level ( r = 0 . 21 , P = 0.01 ) . CONCLUSIONS Two dietary interventions that successfully lowered serum cholesterol levels had no adverse effect on mood . There was some evidence for a relative impairment in cognitive function in the treated groups in one of four cognitive tests , but additional studies will be required to determine the relevance of this finding BACKGROUND Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer 's disease . METHODS In a double-blind study , we evaluated subjects with the amnestic subtype of mild cognitive impairment . Subjects were r and omly assigned to receive 2000 IU of vitamin E daily , 10 mg of donepezil daily , or placebo for three years . The primary outcome was clinical ly possible or probable Alzheimer 's disease ; secondary outcomes were cognition and function . RESULTS A total of 769 subjects were enrolled , and possible or probable Alzheimer 's disease developed in 212 . The overall rate of progression from mild cognitive impairment to Alzheimer 's disease was 16 percent per year . As compared with the placebo group , there were no significant differences in the probability of progression to Alzheimer 's disease in the vitamin E group ( hazard ratio , 1.02 ; 95 percent confidence interval , 0.74 to 1.41 ; P=0.91 ) or the donepezil group ( hazard ratio , 0.80 ; 95 percent confidence interval , 0.57 to 1.13 ; P=0.42 ) during the three years of treatment . Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group , the donepezil group had a reduced likelihood of progression to Alzheimer 's disease during the first 12 months of the study ( P=0.04 ) , a finding supported by the secondary outcome measures . Among carriers of one or more apolipoprotein E epsilon4 alleles , the benefit of donepezil was evident throughout the three-year follow-up . There were no significant differences in the rate of progression to Alzheimer 's disease between the vitamin E and placebo groups at any point , either among all patients or among apolipoprotein E epsilon4 carriers . CONCLUSIONS Vitamin E had no benefit in patients with mild cognitive impairment . Although donepezil therapy was associated with a lower rate of progression to Alzheimer 's disease during the first 12 months of treatment , the rate of progression to Alzheimer 's disease after three years was not lower among patients treated with donepezil than among those given placebo Objective XXXto assess the effect on cognition of a controlled intervention testing Mediterranean diets ( MedDiet ) . Design XXXr and omized trial after 6.5 years of nutritional intervention . Setting Eight primary care centers affiliated to the University of Navarra . Participants A r and om sub sample of 285 participants ( 95 r and omly allocated to each of 3 groups ) of the PREDIMED-NAVARRA trial . All of them were at high vascular risk ( 44.8 % men , 74.1± 5.7 years at cognitive evaluation ) . Interventions Nutritional intervention comparing two MedDiets ( supplemented with extra-virgin olive oil [ EVOO ] or mixed nuts ) versus a low-fat control diet . Participants received intensive education to increase adherence to the intended intervention . Participants allocated to the MedDiet groups received EVOO ( 1 l/week ) or 30 g/day of mixed nuts . Dietary habits were evaluated using a vali date d 137-item food frequency question naire ( FFQ ) . Additionally , adherence to MedDiet was appraised using a 14-item question naire both at baseline and yearly thereafter . Measurements XXXcognitive performance as a main outcome and cognitive status ( normal , mild cognitive impairment [ MCI ] or dementia ) as a secondary outcome were evaluated by two neurologists blinded to group assignment after 6.5 years of nutritional intervention . Results Better post-trial cognitive performance versus control in all cognitive domains and significantly better performance across fluency and memory tasks were observed for participants allocated to the MedDiet+EVOO group . After adjustment for sex , age , education , apolipoprotein E genotype , family history of cognitive impairment/dementia , smoking , physical activity , body mass index , hypertension , dyslipidaemia , diabetes , alcohol and total energy intake , this group also showed lower MCI ( OR=0.34 95 % CI : 0.12–0.97 ) compared with control group . Participants assigned to MedDiet+Nuts group did not differ from controls . Conclusion A long-term intervention with an EVOO-rich MedDiet result ed in a better cognitive function in comparison with a control diet . However , non-significant differences were found for most cognitive domains . Participants allocated to an EVOO-rich MedDiet had less MCI than controls In the PAQUID ( Personnes Agées Quid ) study , the authors prospect ively examined flavonoid intake in relation to cognitive function and decline among subjects aged 65 years or older . A total of 1,640 subjects free from dementia at baseline in 1990 and with reliable dietary assessment were reexamined four times over a 10-year period . Cognitive functioning was assessed through three psychometric tests ( Mini-Mental State Examination , Benton 's Visual Retention Test , " Isaacs " Set Test ) at each visit . Information on flavonoid intake was collected at baseline . A linear mixed model was used to analyze the evolution of cognitive performance according to quartiles of flavonoid intake . After adjustment for age , sex , and educational level , flavonoid intake was associated with better cognitive performance at baseline ( p = 0.019 ) and with a better evolution of the performance over time ( p = 0.046 ) . Subjects included in the two highest quartiles of flavonoid intake had better cognitive evolution than did subjects in the lowest quartile . After 10 years ' follow-up , subjects with the lowest flavonoid intake had lost on average 2.1 points on the Mini-Mental State Examination , whereas subjects with the highest quartile had lost 1.2 points . This gradient persisted after adjustment for several other potential confounders . This study raises the possibility that dietary flavonoid intake is associated with better cognitive evolution There is evidence from a population -based study of an inverse relationship between monounsaturated fatty acids ( MUFA ) energy intake and age-related cognitive decline ( ARCD ) , while high polyunsaturated fatty acids ( PUFA ) intake was positively associated with cognitive impairment in elderly subjects . We investigated the possible role of MUFA and PUFA on age-related cognitive changes . A population -based , prospect i ve study was carried out on 278 , 186 , and 95 nondemented elderly subjects ( 65 - 84 years ) evaluated for global cognitive functions ( Mini-Mental State Examination , MMSE ) at the first ( 1992 - 1993 ) , second ( 1995 - 1996 ) , and third survey ( 2000 - 2001 ) , respectively , from the r and omized cohort of Casamassima , Bari , Italy ( n=704 ) , one of the eight centers of the Italian Longitudinal Study on Aging ( ILSA ) . MUFA and PUFA intakes were assessed at baseline with a semi-quantitative food frequency question naire . High MUFA and PUFA energy intakes and total energy intake were significantly associated with a better cognitive performance in a 8.5-year follow-up . In this prospect i ve population -based study on older nondemented subjects with a typical Mediterranean diet , high MUFA and PUFA intakes appeared to be protective against ARCD OBJECTIVES To identify dietary and lifestyle variables that may affect cognitive function in the elderly . DESIGN Population -based prospect i ve cohort study . SETTING General community residing in Athens and the surrounding Attica region of Greece . SUBJECTS A total of 732 men and women , 60 years or older , participating in the EPIC-Greece cohort ( European Prospect i ve Investigation into Cancer and Nutrition ) and residing in the Attica region had sociodemographic , anthropometric , medical , dietary and lifestyle variables ascertained at enrolment ( 1993 - 1999 ) . Six to 13 years later , cognitive function was evaluated through the Mini-Mental State Examination ( MMSE ) score and affective state through the Geriatric Depression Scale ( GDS ) . RESULTS MMSE score was positively associated with years of formal education , height and physical activity and inversely with age , diabetes mellitus and GDS score ( P < 0.05 for all ) . Among dietary variables , intake of PUFA was inversely associated with cognitive function and this association was largely accounted for by a similar association with seed oils . Adherence to the Mediterranean diet , as well as intake of olive oil , MUFA and SFA exhibited weakly positive but not significant associations . CONCLUSION Physical activity and early life factors as reflected in height are significant predictors of cognitive function in the elderly . Seed oil consumption may adversely affect cognition , whereas other nutritional factors do not appear to have a quantitatively large effect OBJECTIVES We studied the effect of the Mediterranean diet on plasma levels of C-reactive protein ( CRP ) , white blood cell counts , interleukin (IL)-6 , tumor necrosis factor (TNF)-alpha , amyloid A , fibrinogen , and homocysteine . BACKGROUND To the best of our knowledge , the mechanism(s ) by which the Mediterranean diet reduces cardiovascular risk are not well understood . METHODS During the 2001 to 2002 period , we r and omly enrolled 1,514 men ( 18 to 87 years old ) and 1,528 women ( 18 to 89 years old ) from the Attica area of Greece ( of these , 5 % of men and 3 % of women were excluded because of a history of cardiovascular disease ) . Among several factors , adherence to the Mediterranean diet was assessed by a diet score that incorporated the inherent characteristics of this diet . Higher values of the score meant closer adherence to the Mediterranean diet . RESULTS Participants who were in the highest tertile of the diet score had , on average , 20 % lower CRP levels ( p = 0.015 ) , 17 % lower IL-6 levels ( p = 0.025 ) , 15 % lower homocysteine levels ( p = 0.031 ) , 14 % lower white blood cell counts ( p = 0.001 ) , and 6 % lower fibrinogen levels ( p = 0.025 ) , as compared with those in the lowest tertile . The findings remained significant even after various adjustments were made . Borderline associations were found regarding TNF-alpha ( p = 0.076 ) , amyloid A levels ( p = 0.19 ) , and diet score . CONCLUSIONS Adherence to the traditional Mediterranean diet was associated with a reduction in the concentrations of inflammation and coagulation markers . This may partly explain the beneficial actions of this diet on the cardiovascular system Objective Previous observational studies reported beneficial effects of the Mediterranean diet ( MedDiet ) on cognitive function , but results were inconsistent . We assessed the effect on cognition of a nutritional intervention using MedDiets in comparison with a low-fat control diet . Methods We assessed 522 participants at high vascular risk ( 44.6 % men , age 74.6 ± 5.7 years at cognitive evaluation ) enrolled in a multicentre , r and omised , primary prevention trial ( PREDIMED ) , after a nutritional intervention comparing two MedDiets ( supplemented with either extra-virgin olive oil ( EVOO ) or mixed nuts ) versus a low-fat control diet . Global cognitive performance was examined by Mini-Mental State Examination ( MMSE ) and Clock Drawing Test ( CDT ) after 6.5 years of nutritional intervention . Research ers who assessed the outcome were blinded to group assignment . We used general linear models to control for potential confounding . Results After adjustment for sex , age , education , Apolipoprotein E genotype , family history of cognitive impairment/dementia , smoking , physical activity , body mass index , hypertension , dyslipidaemia , diabetes , alcohol and total energy intake , participants allocated to the MedDiet+EVOO showed higher mean MMSE and CDT scores with significant differences versus control ( adjusted differences : + 0.62 95 % CI + 0.18 to + 1.05 , p=0.005 for MMSE , and + 0.51 95 % CI + 0.20 to + 0.82 , p=0.001 for CDT ) . The adjusted means of MMSE and CDT scores were also higher for participants allocated to the MedDiet+Nuts versus control ( adjusted differences : + 0.57 ( 95 % CI + 0.11 to + 1.03 ) , p=0.015 for MMSE and + 0.33 ( 95 % CI + 0.003 to + 0.67 ) , p=0.048 for CDT ) . These results did not differ after controlling for incident depression . Conclusions An intervention with MedDiets enhanced with either EVOO or nuts appears to improve cognition compared with a low-fat diet . IS RCT BACKGROUND Healthy dietary patterns may protect against age-related cognitive decline , but results of studies have been inconsistent . OBJECTIVE We examined associations between Dietary Approaches to Stop Hypertension (DASH)- and Mediterranean-style dietary patterns and age-related cognitive change in a prospect i ve , population -based study . DESIGN Participants included 3831 men and women ≥65 y of age who were residents of Cache County , UT , in 1995 . Cognitive function was assessed by using the Modified Mini-Mental State Examination ( 3MS ) ≤4 times over 11 y. Diet-adherence scores were computed by summing across the energy-adjusted rank-order of individual food and nutrient components and categorizing participants into quintiles of the distribution of the diet accordance score . Mixed-effects repeated- measures models were used to examine 3MS scores over time across increasing quintiles of dietary accordance scores and individual food components that comprised each score . RESULTS The range of rank-order DASH and Mediterranean diet scores was 1661 - 25,596 and 2407 - 26,947 , respectively . Higher DASH and Mediterranean diet scores were associated with higher average 3MS scores . People in quintile 5 of DASH averaged 0.97 points higher than those in quintile 1 ( P = 0.001 ) . The corresponding difference for Mediterranean quintiles was 0.94 ( P = 0.001 ) . These differences were consistent over 11 y. Higher intakes of whole grains and nuts and legumes were also associated with higher average 3MS scores [ mean quintile 5 compared with 1 differences : 1.19 ( P < 0.001 ) , 1.22 ( P < 0.001 ) , respectively ] . CONCLUSIONS Higher levels of accordance with both the DASH and Mediterranean dietary patterns were associated with consistently higher levels of cognitive function in elderly men and women over an 11-y period . Whole grains and nuts and legumes were positively associated with higher cognitive functions and may be core neuroprotective foods common to various healthy plant-centered diets around the globe OBJECTIVE To determine whether the Mediterranean diet and other dietary variables are predictors of transition from healthy cognitive aging to mild cognitive impairment and cognitive decline . DESIGN Longitudinal . PARTICIPANTS We assessed 1528 individuals , aged 60 - 64 years , who were participating in a prospect i ve epidemiological study of mental health and aging . We tested participants at two time points , 4 years apart , for mild cognitive impairment using either the International Consensus Criteria , impairment on the Clinical Dementia Rating scale ( Clinical Dementia Rating : 0.5 ) , or any of a suite of criteria sets ( any mild cognitive disorder ) . We used logistic regression to assess the dietary predictors of conversion to clinical diagnoses and multiple regression to identify the predictors of cognitive decline ( change in global cognition ) in healthy participants . RESULTS Of the 1528 participants with no cognitive impairment in the first wave of assessment and complete data , 10 participants were diagnosed with mild cognitive impairment , 19 with Clinical Dementia Rating 0.5 , and 37 participants presented with any mild cognitive disorder at follow-up . Adherence to Mediterranean diet was not found to be protective against cognitive decline but excessive caloric intake , and high intake of monounsaturated fats was predictive of mild cognitive impairment . CONCLUSIONS In this large longitudinal investigation of generally healthy individuals Mediterranean diet was not found to be protective of cognitive decline Objective : We sought to determine the relationship of greater adherence to Mediterranean diet ( MeD ) and likelihood of incident cognitive impairment ( ICI ) and evaluate the interaction of race and vascular risk factors . Methods : A prospect i ve , population -based , cohort of individuals enrolled in the Reasons for Geographic and Racial Differences in Stroke ( REGARDS ) Study 2003–2007 , excluding participants with history of stroke , impaired cognitive status at baseline , and missing data on Food Frequency Question naires ( FFQ ) , was evaluated . Adherence to a MeD ( scored as 0–9 ) was computed from FFQ . Cognitive status was evaluated at baseline and annually during a mean follow-up period of 4.0 ± 1.5 years using Six-item-Screener . Results : ICI was identified in 1,248 ( 7 % ) out of 17,478 individuals fulfilling the inclusion criteria . Higher adherence to MeD was associated with lower likelihood of ICI before ( odds ratio [lsqb]OR[rsqb ] 0.89 ; 95 % confidence interval [lsqb]CI[rsqb ] 0.79–1.00 ) and after adjustment for potential confounders ( OR 0.87 ; 95 % CI 0.76–1.00 ) including demographic characteristics , environmental factors , vascular risk factors , depressive symptoms , and self-reported health status . There was no interaction between race ( p = 0.2928 ) and association of adherence to MeD with cognitive status . However , we identified a strong interaction of diabetes mellitus ( p = 0.0134 ) on the relationship of adherence to MeD with ICI ; high adherence to MeD was associated with a lower likelihood of ICI in nondiabetic participants ( OR 0.81 ; 95 % CI 0.70–0.94 ; p = 0.0066 ) but not in diabetic individuals ( OR 1.27 ; 95 % CI 0.95–1.71 ; p = 0.1063 ) . Conclusions : Higher adherence to MeD was associated with a lower likelihood of ICI independent of potential confounders . This association was moderated by presence of diabetes mellitus There are surprisingly few r and omised , controlled trials into the effects of dietary change on mood and cognition in healthy individuals . Here we examined the effects of 10 days of changing to a nutrient-rich diet on mood and cognitive performance . Young female adults ( N=25 ) were r and omised to a diet change ( DC ) , or a no change ( NC ) control group . Those in the DC condition adhered to the nutrient-dense Mediterranean diet . Mood and cognitive performance were assessed at baseline and on day 10 . Compared with the NC group , the DC group showed significant improvements in self-rated vigour , alertness and contentment . Changes in cognitive tasks were somewhat inconsistent . These preliminary findings require verification in larger trials but suggest that appropriate dietary change may benefit mood and some aspects of cognitive performance in healthy adults BACKGROUND Cardiovascular disease and vascular risk factors increase rates of cognitive impairment , but very little is known regarding prevention in this high-risk group . The heart-healthy Mediterranean-type dietary pattern may beneficially influence both vascular and cognitive outcomes . OBJECTIVES We examined the association between Mediterranean-style diet and cognitive decline in women with prevalent vascular disease or ≥3 coronary risk factors . DESIGN / PARTICIPANTS / SETTING Prospect i ve cohort study among 2,504 women participants in the Women 's Antioxidant Cardiovascular Study ( WACS ) , a cohort of female health professionals . Adherence to a Mediterranean-style diet was determined at WACS baseline ( 1995 - 1996 ) using a 0- to 9-point scale with higher scores indicating higher adherence . In 1998 - 2000 , participants aged ≥65 years underwent a telephone cognitive battery including five tests of global cognition , verbal memory , and category fluency . Tests were administered three additional times across 5.4 years . STATISTICAL ANALYSES PERFORMED We used multivariable-adjusted generalized linear models for repeated measures to compare the annual rates of cognitive score changes across tertiles of Mediterranean diet score , as assessed at WACS baseline . RESULTS In both basic- and multivariable-adjusted models , consuming a Mediterranean-style diet was not related to cognitive decline . No effect modification was detected by age , education , depression , cardiovascular disease severity at WACS baseline , or level of cognition at initial assessment . CONCLUSIONS In women at higher risk of cognitive decline due to vascular disease or risk factors , adherence to a Mediterranean-style diet was not associated with subsequent 5-year cognitive change Objectives : We examined whether accordance to the DASH ( Dietary Approach to Stop Hypertension ) and Mediterranean diets is associated with slower cognitive decline in a prospect i ve Chicago cohort study of older persons , the Memory and Aging Project . Methods : The sample comprised 826 Memory and Aging Project participants ( aged 81.5 ± 7.1 years ) who completed a 144-item food frequency question naire at baseline and 2 or more cognitive assessment s over 4.1 years . Dietary scores were computed for accordance to the DASH diet ( 0–10 ) and the Mediterranean diet ( MedDietScore ) ( 0–55 ) . For both , higher scores reflect greater accordance . Both patterns share at least 3 common food components . Cognitive function was assessed annually with 19 cognitive tests from which global cognitive scores and summary measures are computed . Results : The mean global cognitive score at baseline was 0.12 ( range , −3.23 to 1.60 ) with an overall mean annual change in score of −0.08 st and ardized units . Only 13 participants had possible dementia . The mean DASH score was 4.1 ( range , 1.0–8.5 ) and the MedDietScore was 31.3 ( range , 18–46 ) . In mixed models adjusted for covariates , a 1-unit difference in DASH score was associated with a slower rate of global cognitive decline by 0.007 st and ardized units ( st and ard error of estimate = 0.003 , p = 0.03 ) . Similarly , a 1-unit-higher MedDietScore was associated with a slower rate of global cognitive decline by 0.002 st and ardized units ( st and ard error of estimate = 0.001 , p = 0.01 ) . Conclusions : These findings support the hypothesis that both the DASH and Mediterranean diet patterns are associated with slower rates of cognitive decline in the same cohort of older persons In this large-scale prospect i ve epidemiological study , we examined associations of long-term adherence to the Mediterranean diet ( MeDi ) and subsequent cognitive function and decline . We included 16,058 women from the Nurses ' Health Study , aged ≥70 y , who underwent cognitive testing by telephone 4 times during 6 y , beginning in 1995 - 2001 , and provided repeated information on diet between 1984 and the first cognitive exam . Primary outcomes were the Telephone Interview for Cognitive Status ( TICS ) and composite scores of verbal memory and global cognition . MeDi adherence was based on intakes of : vegetables , fruits , legumes , whole grains , nuts , fish , red and processed meats , moderate alcohol , and the ratio of monounsaturated : saturated fat . Long-term MeDi exposure was estimated by averaging all repeated measures of diet ( > 13 y , on average ) . In primary analyses of cognitive change , the MeDi was not associated with decline in global cognition or verbal memory . In a secondary approach examining cognitive status in older age , determined by averaging all 4 repeated measures of cognition , each higher quintile of long-term MeDi score was linearly associated with better multivariable-adjusted mean cognitive scores [ differences in mean Z-scores between extreme quintiles of MeDi = 0.06 ( 95 % CI : 0.01 , 0.11 ) ; = 0.05 ( 95 % CI : 0.01 , 0.08 ) ; and = 0.06 ( 95 % CI : 0.03 , 0.10 ) st and ard units ; P-trends = 0.004 , 0.002 , and < 0.001 for TICS , global cognition , and verbal memory , respectively ] . These associations were similar to those observed in women 1 - 1.5 y apart in age . In summary , long-term MeDi adherence was related to moderately better cognition but not with cognitive change in this very large cohort of older women |
1,635 | 22,325,958 | CONCLUSIONS Use of MECC in heart surgery result ed in improved short-term outcome as reflected by reduced mortality and morbidity compared with conventional extracorporeal circulation | BACKGROUND The question whether use of minimal extracorporeal circulation ( MECC ) influences patients ' outcome remains unanswered .
We performed a systemic review of the literature and a meta- analysis of r and omized controlled trials to evaluate the impact of MECC compared to conventional extracorporeal circulation ( CECC ) on mortality and major adverse cardiovascular events in patients undergoing heart surgery . | Objective : We examined intraoperative microembolic signals ( GME ) , inflammatory response , hemolysis , perioperative regional cerebral oxygen saturation ( rSO2 ) , myocardial protection and desorbed protein amount on oxygenator fibers in high-risk patients undergoing coronary revascularization ( CABG ) with minimized and conventional cardiopulmonary bypass ( CPB ) . Methods : Over a ten-month period , 40 Euroscore 6 + patients undergoing CABG were prospect ively r and omized to one of the two perfusion protocol s ( N=20 ) : Group 1 : minimized extracorporeal circuits ( Mini-CPB ) ( ROCsafe MPC , Terumo , Ann Arbor , MI , USA ) and Group 2 : conventional extracorporeal circuits ( CECC ) ( Capiox SX18 , Terumo , USA ) . Serum creatinine kinase-MB ( CKMB ) , free hemoglobin , interleukin-6 ( IL-6 ) and C3a levels were measured . Blood sample s were collected at T1 : following induction of anesthesia ; T2 : thromboelastography control ; T3:15 min after commencement of CPB ; T4 : before cessation of CPB ; T5 : 15 min after protamine reversal and T6 : ICU . Results : Serum IL-6 levels were significantly lower in the Mini-CPB group at T4 and T5 and C3a levels were significantly less in the Mini-CPB group at T3 , T4 and T5 vs. CECC ( p<0.01 ) . CKMB levels in coronary sinus blood demonstrated well preserved myocardium in the Mini-CPB group . Percentage expression of neutrophil CD11b/CD18 levels were significantly lower in the Mini-CPB group at T4 and T5 ( p<0.05 ) . There were no significant differences in air h and ling characteristics or free plasma hemoglobin levels in either circuit . rSO2 measurements were significantly better at T3 and T4 in the Mini-CPB vs. CECC ( p<0.05 ) and always higher in the Mini-CPB during follow-up . Blood protein adsorption analysis of oxygenator membranes demonstrated a significantly increased amount of microalbumin on CECC fibers ( p<0.05 ) . Conclusion : Mini-CPB provided a comfort and safety level similar to conventional control via satisfactory air h and ling , attenuated inflammatory response and hemodilution , with a better clinical outcome in patients undergoing high-risk CABG In this prospect i ve cohort study we addressed the clinical impact of a reduced anticoagulation protocol on the hospital outcome of patients undergoing coronary revascularization with cardiopulmonary bypass . 364 consecutive low to moderate risk patients scheduled for elective isolated coronary operations were admitted to the study . 184 patients ( Control Group ) received conventional open circuits and full systemic anticoagulation ( target activated clotting time 480 seconds ) ; 180 patients ( Intraoperative ECMO group ) received closed , phosphorylcholine coated circuits and a reduced systemic heparin dose ( target activated clotting time 320 seconds ) . Patients of the Intraoperative ECMO group had less requirement for allogeneic blood products ( odds ratio 0.55 , 95 % confidence interval 0.34–0.92 , p= 0.02 ) , a significant containment of blood loss ( 374 ± 278 mL vs. 463 ± 321 mL in Control group , p= 0.005 ) a lower postoperative peak serum creatinine levels ( 1.19 ± 0.48 mg/dL vs. 1.41 ± 0.94 mg/dL in Control group , p= 0.048 ) , and a significant lower rate of severe morbidity ( odds ratio 0.27 , 95 % confidence interval 0.09–0.81 , p= 0.02 ) . A reduction of systemic anticoagulation is feasible with a non-heparin-bonded , closed biocompatible circuit , and results in a significant improvement of the outcome of low to moderate risk coronary patients PURPOSE Inflammation and coagulation disturbances are common consequences of cardiopulmonary bypass ( CPB ) . Recently , miniaturized closed CPB circuits without cardiotomy suction and venous reservoir have been proposed to reduce complication rates . We compared outcomes with conventional ( CCPB ) and miniaturized cardiopulmonary bypass ( MCPB ) after coronary artery bypass operations ( CABG ) with respect to inflammation and coagulation . DESCRIPTION Thirty patients ( 23 % female ; aged 67.9 + /- 9.0 years ) were prospect ively r and omly assigned to undergo isolated CABG with CCPB or MCPB . Conventional CPB had a pump prime of 1 , 600 mL. Miniaturized CPB consisted of a centrifugal pump , arterial filter , heparinized tubing , and oxygenator with a priming volume of 800 mL. Shed blood was removed by a cell-saving device and reinfused . Measurements included interleukin (IL)-2 receptor , IL-6 , IL-10 , tumor necrosis factor receptor 55 and 75 , C reactive protein , leukocyte differentiation , d-dimers , fibrinogen , and thrombocytes at six time points . EVALUATION In both groups no major complication occurred . However , two dangerous air leaks occurred in the closed MCPB circuit , demonstrating the narrow safety margins . Operative h and ling was also more difficult owing to limitations in venting and fluid management . International normalized ratio ( p = 0.03 ) and antithrombin III ( p = 0.04 ) levels were elevated during CPB in the CCPB group , most likely owing to differences of the intraoperative anticoagulation management . Repeated measures analysis revealed that not a single parameter of inflammation or clinical outcome showed significant differences among groups . CONCLUSIONS Use of a MCPB affected inflammation and coagulation variables only marginally and did not lead to clinical relevant changes as assessed by blood loss , need for blood products , and intensive care unit and clinical stays . However , safety margins for volume loss , air emboli , and weaning from CPB decrease , because of the closed MCPB circuit Objectives . Cardiopulmonary bypass ( CPB ) is known to cause the systemic inflammatory reaction after cardiac surgery . New coated and closed loop circuit systems may reduce this inflammation response and improve the surgical outcome . This study was design ed to evaluate the safety and efficacy of the mini-extracorporeal circulation system ( ECC.O ) in CABG patients . Design . Forty patients undergoing elective coronary surgery were r and omized into two groups , the ECC.O group and the st and ard CPB group . Routine hemodynamic monitoring and biochemical measurements were registered according to the hospital practice . Results . The clinical outcome of the patients was similar in both groups . There were no significant differences between the groups in the duration of intubation following surgery , the length of intensive care unit-stay or the total hospital stay . The haemoglobin level was significantly higher ( p=0.0069 ) during and after the perfusion in the ECC.O group . Conclusions . The ECC.O system can be safely used in CABG patients and it maintains haemoglobin level better than conventional CPB OBJECTIVE Coronary artery bypass grafting with cardiopulmonary bypass carries a risk for neurologic complications because of cerebral hypoperfusion and microembolization . The basic goals of a novel closed minimized extracorporeal circulation are to prevent excessive hemodilution and to avoid blood-air interface . The aim of this prospect i ve r and omized study was to determine the effect of using the minimized extracorporeal circulation system compared with open conventional extracorporeal circulation on cerebral tissue oxygenation and microembolization . METHODS Forty patients undergoing coronary artery bypass grafting ( 20 in each group ) were continuously monitored for changes in cerebral oxygenated hemoglobin and tissue oxygenation index by using near-infrared spectroscopy . Total microembolic count and gaseous embolic count in both median cerebral arteries were monitored with multifrequency transcranial Doppler instrumentation . RESULTS In the conventional extracorporeal circulation group there was a highly significant reduction in both cerebral oxygenated hemoglobin and tissue oxygenation index from the start to the end of cardiopulmonary bypass ( P < .01 ) . The rate of decrease in cerebral oxygenated hemoglobin after aortic cannulation was faster in the conventional extracorporeal circulation group ( F test = 9.03 , P < .001 ) . No significant changes with respect to cerebral oxygenated hemoglobin or tissue oxygenation index occurred in the minimized extracorporeal circulation group , except at the beginning of rewarming ( P < .01 ) . Total embolic count , as well as gaseous embolic count , in the left and right median cerebral arteries was significantly lower in the minimized extracorporeal circulation group ( all P < .05 ) . Postoperative bleeding was greater ( P < .05 ) and the transfusion rate was higher ( P < .05 ) in the conventional extracorporeal circulation group . CONCLUSIONS Use of closed minimized cardiopulmonary bypass compared with conventional open cardiopulmonary bypass preserves cerebral tissue oxygenation and reduces cerebral microembolization Neutrophil gelatinase-associated lipocalin ( NGAL ) has been implicated as an early predictive urinary biomarker of ischemic acute kidney injury ( AKI ) . The aim of this study was to compare the effects of miniaturized cardiopulmonary bypass system ( MCPB ) vs. st and ard cardiopulmonary bypass system ( SCPB ) system on kidney tissue in patients undergoing myocardial revascularization using urinary NGAL levels as an early marker for renal injury . Sixty consecutive patients who underwent myocardial revascularization were studied prospect ively . An SCPB was used in 30 patients ( group A ) and MCPB was used in 30 patients ( group B ) . The SCPB group but not the MCPB group showed a significant NGAL concentration increase from preoperative during the 1st postoperative day ( 169.0+/-163.6 ng/ml in the SCPB group vs. 94.1+/-99.4 ng/ml in the MCPB group , P<0.05 , respectively ) . Two patients in the SCPB group developed AKI and underwent renal replacement therapy ; no patient in MCPB developed AKI . The MCPB system is safe in routine clinical use . Kidney function is better protected during MCPB as demonstrated by NGAL levels . NGAL represents an early biomarker of renal failure in patients undergoing cardiac surgery and the valuation of its concentration can aid in medical decision-making OBJECTIVE Minimal extracorporeal circulation ( mini-ECC ) is a new technology , consisting of a centrifugal pump , an oxygenator , and a modified suction system . The main advantage of mini-ECC is the reduction of tubing length ( reduction of the priming volume ) . Additional beneficial effects are a decrease of coagulation cascade and a reduction of blood transfusion in patients undergoing coronary artery bypass grafting ( CABG ) surgery . We compared the intraoperative and early postoperative myocardial damage and outcome of patients who underwent CABG surgery with conventional cardiopulmonary bypass ( CPB ) or mini-ECC . METHODS One hundred and thirty-six consecutive patients who underwent isolated CABG surgery at our institution were prospect ively studied . Fifty-four patients ( 39.7 % ) were operated with mini-ECC . Patient characteristics were similar in both groups . The most interesting intraoperative details as well as in-hospital outcome were assessed . RESULTS There was no difference in mortality between the two groups . Cross-clamping time was similar in both groups ( p = 0.07 ) . Defibrillation was required in one patient in the mini-ECC group ( 1.9 % ) and in 38 patients ( 46.3 % ) in the CPB group ( p < 0.001 ) . In the mini-ECC group , the requirement of inotropic support and incidence of atrial fibrillation was significantly lower than in the CPB group . Postoperative creatine kinase isoenzyme MB ( CK-MB ) and cardiac Troponin I ( cTnI ) were significantly lower in the mini-ECC group ( p < 0.05 ) . Duration of ventilation , length of stay in the intensive care unit and total hospitalization time were significantly shorter in patients operated with mini-ECC ( p < 0.05 ) . CONCLUSION Mini-ECC is a safe procedure and is followed by a diminished release of CK-MB and cTnI than after CPB . Postoperative recovery is accelerated following mini-ECC and there is a significantly lower incidence of postoperative atrial fibrillation BACKGROUND The purpose of this study was to evaluate the safety and clinical results of aortic valve replacement performed with minimally invasive closed circuit extracorporeal circulation technique ( MECC system ) versus st and ard cardiopulmonary bypass . METHODS Forty consecutive patients undergoing isolated aortic valve replacement at a single institution were r and omly assigned to either miniaturized closed circuit cardiopulmonary bypass with the Maquet-Cardiopulmonary ( Rastatt , Germany ) minimal extracorporeal circulation ( MECC ) system ( study group B , n = 17 ) or st and ard cardiopulmonary bypass ( control group A , n = 23 ) . The MECC system is a low priming circuit without blood-air interface . Technical feasibility , in particular the potential entry of air in the circuit , and clinical results were prospect ively evaluated . RESULTS Demographic characteristics and surgical data were similar in both groups . Patients in the study group showed reduced chest tube drainage ( 217 + /- 62 mL vs 420 + /- 219 mL , p < 0.05 ) and blood transfusion requirements ( 5.1 % vs 43.4 % , p < 0.02 ) compared with patients in the control group . Moreover , the study group showed significantly higher time course of hematocrit at all time points during the operation and longer hospital stay ( p < 0.02 ) than the control group ; similarly , in the study group patients ' platelet count in intensive care unit admission was significantly higher than the control group ( 140 + /- 29 x 10(9)/L vs 119 + /- 37 x 10(9)/L , p < 0.05 ) . Peak postoperative troponin C release was significantly lower in the study group ( 4.74 + /- 2.82 vs 8.43 + /- 6.25 ng/dL , p < 0.033 ) . One patient undergoing the MECC system operation showed a major neurologic event on postoperative day four , which was probably secondary to severe aortic calcification . CONCLUSIONS The MECC system is suitable for aortic valve replacement and provides better clinical results than st and ard cardiopulmonary bypass as regards blood transfusion requirements , platelets consumption , and myocardial damage OBJECTIVE Minimised perfusion circuits ( MPCs ) are expected to reduce the side effects of conventional cardiopulmonary bypass ( CCPB ) ; however , conclusive data from sufficiently powered clinical trials are lacking . The purpose of this study was to evaluate the safety and efficacy of the ROCsafeRX minimised perfusion circuit . METHODS A r and omised , controlled , multicentre clinical trial comparing both perfusion circuits in patients subjected to elective coronary artery bypass and /or aortic valve replacement is described . The primary end points of safety , defined as procedure success without device-related complications , and secondary end point of efficacy , including reduction of transfusion requirement and incidence of atrial fibrillation , are analysed . RESULTS To date , 291 patients have been enrolled and r and omised ( 146 MPC vs 145 CCPB ) . With the exception of a significantly higher male population in the MPC group ( 83.6 % vs 71.0 % , p=0.01 ) , both groups were well matched for demographic data and type of surgery . There were no device-related complications but a hard-shell reservoir had to be integrated in one MPC because of a tear in the right atrium that was managed uneventfully . Total transfusion requirement ( 329+/-599 ml vs 783+/-1638 ml , p < or = 0.001 ) and erythrocyte transfusion ( 181+/-341 ml vs 434+/-798 ml , p < or = 0.001 ) were significantly reduced in the MPC group . The incidence of atrial fibrillation was significantly lower in the MPC group ( 7.1 % vs 19.5 % , p < or = 0.01 ) , while freedom of major adverse events showed no significant difference . CONCLUSIONS Lack of device-related complications combined with a significant reduction in postoperative atrial fibrillation and transfusion requirements have shown the ROCsafeRX MPC to be both safe and efficient for large-scale use in cardiac patients . Additional data are expected to confirm these initial findings BACKGROUND Minimized extracorporeal circulation is intended to reduce the negative effects associated with cardiopulmonary bypass . This prospect i ve study was performed to evaluate whether minimized extracorporeal circulation has a clinical benefit for coronary artery surgery patients compared to st and ard extracorporeal circulation . METHODS Sixty patients were r and omized into two study groups : 30 patients underwent coronary artery bypass grafting using minimized extracorporeal circulation and 30 patients were operated using st and ard extracorporeal circulation . Baseline characteristics , intraoperative details , postoperative data , perioperative blood chemistry determinations of hematocrit , platelets , muscle-brain fraction of the creatine kinase , cardiac troponin T and colloid osmotic pressure as measurements of intrathoracic blood volume index and extravascular lung water index were compared . RESULTS Baseline characteristics and intraoperative details of both groups were similar . Patients who underwent minimized extracorporeal circulation showed more short-term dependency on norepinephrine ( P < 0.01 ) . Their maximal postoperative muscle-brain fraction of the creatine kinase was lower ( P < 0.05 ) and their hematocrit on arrival in the intensive care unit was higher ( P < 0.01 ) . No other significant differences were found . In both collectives , values for hematocrit ( P < 0.001 ) , platelets ( P < 0.001 ) , colloid osmotic pressure ( P < 0.001 ) and intrathoracic blood volume index ( P < 0.05 ) decreased , while the extravascular lung water index did not change significantly during cardiopulmonary bypass . CONCLUSIONS A clinical advantage of minimized over st and ard extracorporeal circulation was not found . Furthermore , a higher number of patients in the minimized extracorporeal circulation group required postoperative norepinephrine infusions for hemodynamic stabilization . In summary , the presumed superiority of minimized extracorporeal circulation for coronary artery bypass grafting in st and ard patients could not be confirmed The aim of this study was to compare the systemic blood activation with open and closed perfusion management during cardiopulmonary bypass . In 30 patients undergoing coronary artery bypass grafting , we prospect ively studied systemic blood activation , blood loss and the need for donor blood . In 15 patients we used an open venous reservoir consisting of a hard shell venous reservoir with an integrated cardiotomy filter . In another 15 patients we used a totally closed venous reservoir consisting of a collapsible venous reservoir , no coronary suction , modified vent and cell saver . Venous blood sample s were collected pre , post and 24 hours postoperatively . Sex , age and perfusion times were identical in both groups . There were no statistically significant differences in concentrations of FXIIa and C3a , amount of blood loss and need for donor blood . Interleukin-6 and Elastase levels showed trends toward a lesser inflammatory reaction in closed venous reservoir patients . Modification of perfusion management with optimized air management does not seem to be an effective strategy in reducing the inflammatory response and influencing the coagulation system in this small cohort OBJECTIVE Oxidative stress as a result of reperfusion injury is a known causative factor of cardiac muscle injury . In the peripheral blood as well in the coronary sinus , oxidative stress parameters and cardiac biomarkers were measured to investigate the different levels of oxidative stress during three different CABG techniques ; MCABG ( with minimal prime volume and warm blood cardioplegia ) that was newly introduced in our hospital , versus OPCAB , versus our current st and ard , conventional CABG ( CCABG , consisting of high volume prime and cold crystalloid cardioplegia ) . Concomitantly , cardiac biomarkers were measured to detect myocardial cell injury . METHODS Thirty patients scheduled for CABG with the intention to treat three-vessel disease were r and omly assigned for CCABG , MCABG or OPCAB . Perioperatively , plasma levels of malondialdehyde ( MDA ) as a marker of oxidative stress , and the allantoin/uric acid ratio ( A/U ratio ) as a marker of antioxidant activity were measured in the ascending aorta ( Aa ) , and in the coronary sinus ( Cs ) , simultaneously . Additionally peripheral ( Aa ) blood levels of heart fatty acid binding protein ( HFABP ) , troponin T , CPK and CKMB as markers of myocardial injury were obtained . RESULTS The MCABG group had significantly lower MDA levels in the Cs compared to the CCABG group , respectively , to the OPCAB group ( p=0.04 and p=0.03 ) . At all time points the A/U ratio in the CCABG group remained significantly higher in the Cs as well in the Aa sample s compared to the MCABG and the OPCAB group ( p<0.001 , respectively , p<0.001 , for both groups ) . HFABP and troponin T showed consistent curves compared to the CPK figure over time in all groups . CONCLUSION In this study coronary sinus blood levels of oxidative stress parameters were consistently higher compared to peripheral blood levels . The levels were lowest in the MCABG study group . In this group also the lowest levels cardiac biomarkers of myocardial injury were found Introduction Many innovative cardiopulmonary bypass ( CPB ) systems have recently been proposed by the industry . With few differences , they all share a philosophy based on priming volume reduction , closed circuit with separation of the surgical field suction , centrifugal pump , and biocompatible circuit and oxygenator . These minimally invasive CPB ( MICPB ) systems are intended to limit the deleterious effects of a conventional CPB . However , no evidence exists with respect to their effectiveness in improving the postoperative outcome in a large population of patients . This study aim ed to verify the clinical impact of an MICPB in a large population of patients undergoing coronary artery revascularization . Methods We conducted a retrospective analysis of 1,663 patients treated with an MICPB . The control group ( conventional CPB ) was extracted from a series of 2,877 patients according to a propensity score analysis . Results Patients receiving an MICPB had a shorter intensive care unit ( ICU ) stay , had lower peak postoperative serum creatinine and bilirubin levels , and suffered less postoperative blood loss . Within a multivariable model , MICPB is independently associated with lower rates of atrial fibrillation ( odds ratio [ OR ] 0.83 , 95 % confidence interval [ CI ] 0.69 to 0.99 ) and ventricular arrhythmias ( OR 0.45 , 95 % CI 0.28 to 0.73 ) and with higher rates of early discharge from the ICU ( OR 1.31 , 95 % CI 1.06 to 1.6 ) and from the hospital ( OR 1.46 , 95 % CI 1.18 to 1.8 ) . Hospital mortality did not differ between groups . Conclusion MICPBs are associated with reduced morbidity . However , these results will need to be confirmed in a large , prospect i ve , r and omized , controlled trial A compact cardiopulmonary bypass ( CPB ) utilized by closed circuit system with minimized priming volume can be a solution to reduce adverse effects of CPB , and the Resting Heart System ( RHS ; Medtronic , Inc , Minneapolis , MN , USA ) is the newest one on the market . We performed CABG with RHS in 10 patients , and report here our preliminary experiences with RHS in comparison with conventional CPB . Twenty patients who underwent isolated CABG were r and omized into two groups ; RHS group ( n=10 ) with the use of RHS and Conventional group ( n=10 ) with the use of a conventional CPB . There were no significant differences of preoperative patient characteristics in both groups . The mean number of grafts was 2.7+/-0.6 and 2.7+/-0.8 ( P=0.38 ) , the mean aortic clamp was 32+/-11 and 35+/-11 min ( P=0.35 ) , and CPB times were 68+/-25 and 72+/-24 min ( P=0.82 ) in RHS and Conventional group , respectively . All patients but one had no complications and survived in both groups . One patient in RHS group died suddenly on the 5th postoperative day after uneventful postoperative course . Postoperative leukocyte count at 6 h after the operation and value of the C-reactive protein were 11200+/-2310 and 13300+/-3990/mm(3 ) ( P=0.10 ) and 44.4+/-9.7 and 65.3+/-18.5 mg/l ( P=0.045 ) in RHS and Conventional group , respectively . CABG operations could be safely performed using the RHS with a comfort level similar to st and ard CPB Background — We aim ed to evaluate the clinical results and biocompatibility of the minimal extracorporeal circulation system ( MECC ) compared with off-pump coronary revascularization ( OPCABG ) . Methods and Results — In a prospect i ve r and omized study , 150 patients underwent coronary surgery with the use of MECC and 150 underwent OPCABG . End points were ( 1 ) circulating markers of inflammation and organ injury , ( 2 ) operative results , and ( 3 ) outcome at 1-year follow-up . Operative mortality and morbidity were comparable between the groups . Release of inflammatory markers was similar between groups at all time points ( peak interleukin-6 167.2±13.5 versus 181±6.5 pg/mL , P=0.14 , OPCABG versus MECC group , respectively ) . Peak creatine kinase was 419.3±103.5 versus 326±84.2 mg/dL ( P=0.28 ) , and peak S-100 protein was 0.13±0.08 versus 0.29±0.1 pg/mL ( P=0.058 , OPCABG versus MECC group , respectively ) . Length of hospital stay and use of blood products were similar between groups . Two cases of angina recurrence at 1 year in the MECC group were observed versus 5 cases observed in the OPCABG group ( P=0.44 ) . A residual perfusion defect at myocardial nuclear scan was less frequent among patients in the MECC group ( 3 versus 9 cases , P=0.14 ; odds ratio 0.32 , 95 % confidence interval 0.07 to 1.32 ) . Six ( OPCABG group ) versus 3 ( MECC group ) coronary grafts were occluded or severely stenotic at 1 year ( P=0.33 , odds ratio 0.47 , 95 % confidence interval 0.09 to 2.14 ) . Conclusions — Clinical results of coronary revascularization with MECC are optimal when this procedure is performed by experienced teams . Postoperative morbidity is comparable to that with OPCABG . MECC is associated with little pump-related systemic and organ injury . It may achieve the benefits of OPCABG ( less morbidity in high-risk patients ) while facilitating complete revascularization in the case of complex lesions unsuitable for OPCABG BACKGROUND To assess the potential benefits of a new concept of cardiopulmonary bypass ( CPB ) , the mini-extracorporeal circulation ( MECC ) Jostra System , we conducted a prospect i ve r and omized study among patients who underwent coronary artery bypass grafting ( CABG ) with a MECC Jostra System or with a st and ard CPB . METHODS In a prospect i ve r and omized study , 400 patients underwent elective CABG using a st and ard CPB ( 200 patients ) or a Jostra MECC System ( 200 patients ) . The patients were r and omly assigned to have preoperative data similar for both groups . RESULTS The operative mortality rate ( < 30 days ) was 1.5 % for the MECC group and 2.5 % for the CPB group ( P = NS ) . Low-cardiac-output syndrome occurred in 0.66 % and 4 % for the CPB group ( P < .001 . ) . The inflammatory response was significantly reduced with the MECC . Likewise , C-reactive protein release was significantly higher in group B at 24 hours ( 69.6 + /- 38.5 vs 40.8 + /- 21.8 mg/L for the group A , P < .01 ) and at 48 hours ( 116.7 + /- 47.0 vs 65.4 + /- 39.5 mg/L , P < .05 ) postoperatively . In the CPB group , there was a significantly higher decrease of hematocrit and hemoglobin rate . So , the intraoperative transfusion rate amounted to 6 % for the MECC group and 12.8 % for the CPB group ( P < .001 ) . Patients in the CPB group had significantly higher levels of postoperative blood creatinine and urea . CONCLUSION The MECC system is a new concept of CPB that seems to be reliable and safe . To perform CABG , the MECC provides an excellent surgical exposure like a st and ard CPB and a better biologic profile like CABG without CPB The use of miniaturized cardiopulmonary bypass ( CPB ) circuits and avoidance of cardioplegic arrest are attempts to reduce the inflammatory response to cardiac surgery . We studied the effects of beating heart surgery ( BHS ) with assistance of simplified bypass systems ( SBS ) on global hemodynamics , myocardial function and the inflammatory response to CPB . We hypothesized that the use of SBS was associated with less hemodynamic instability after CPB result ing from attenuation of the inflammatory response when compared with surgery performed with a conventional CPB ( cCPB ) circuit . Forty-five patients undergoing coronary artery bypass grafting were prospect ively studied . Fifteen patients were r and omized to the use of a cCPB circuit , cold crystalloid cardioplegia , and moderate hypothermia . Two groups of 15 patients underwent BHS during normothermia with assistance of two different SBS consisting of only blood pump and oxygenator . Hemodynamic variables were assessed with transpulmonary thermodilution and transesophageal echocardiography . Plasma levels of proinflammatory and antiinflammatory mediators were measured perioperatively . After CPB , variables of global hemodynamics and systolic ventricular function did not differ among groups . Left ventricular diastolic function was impaired after CPB equally in all groups ( P < 0.01 versus pre-CPB ) . At the end of surgery , there was more need for vasopressor ( norepinephrine ) support in both SBS groups than in the cCPB group ( P < 0.01 ) . After CPB , the release of interleukin (IL)-6 did not differ significantly among groups , whereas plasma levels of IL-10 were higher in the cCPB group ( P < 0.01 versus SBS ) . The extent of myocardial necrosis ( Troponin T ) was comparable in all groups . We conclude that in our study , miniaturizing bypass systems and avoidance of cardioplegic arrest were not effective in improving hemodynamic performance and in attenuating the proinflammatory immune response after CPB The objective of this study was to investigate the difference between the closed circuit system and the open circuit system in clinical heparin-coated cardiopulmonary bypass ( CPB ) circuits with a centrifugal pump . We evaluated the coagulation , fibrinolysis , and inflammatory response in valvular heart surgery . Nineteen patients were assigned at r and om to a group for the closed circuit system or the open circuit system . This is the first report on the effect of a closed circuit in valvular surgery . We measured the platelet count , white blood cell count , plasma fibrinogen concentration , thrombin – antithrombin III complex , plasmin-Α2 plasmin inhibitor complex , D-dimer , interleukin-6 , polymorphic neutrophil-elastase , and the plasma free hemoglobin . Blood sample s were collected before the start of perfusion , 15 and 60 min after the start of perfusion , 60 min after the administration of protamine , and 1 day after the operation . During the perfusion , coagulation , fibrinolysis , and inflammatory responses were activated ; however , no significant differences between the two groups were noted . In this clinical investigation with suction and the cell saving system , the closed circuit was not found to be superior to the open circuit with regard to biocompatibility OBJECTIVE The study was design ed to determine differences in blood loss and transfusion associated with a minimized cardiopulmonary bypass circuit versus a st and ard bypass circuit . METHODS From February 2005 through April 2006 , 199 patients were r and omized to undergo coronary artery bypass grafting with a st and ard cardiopulmonary bypass circuit ( Medtronic , Inc. , Minneapolis , Minn ) or a minimized bypass circuit , the Medtronic Resting Heart Circuit . Laboratory perimeters ( hemoglobin and platelet count ) , were measured at baseline , after initiation of cardiopulmonary bypass , and on intensive care unit admission . Lowest values recorded were noted . Blood administration was controlled by study -specific protocol orders , ( transfusion for hemoglobin < 8mg% ) . Patient demographic data were retrieved from the Society of Thoracic Surgeons data base . Blood product administration was recorded during hospital admission , and chest tube drainage as total output collected from operating room to discontinuation . Continuous variables were tested with a Wilcoxin rank test , and categoric variables with X(2 ) and Fisher 's exact tests . RESULTS Hematocrit , equivalent at baseline , was higher in minimized circuit cohort at lowest point during cariopulmonary bypass ( 31.5 % + /- 3.9 % vs. 25.5 % + /- 3.7 % ) , after protamine ( 31.6 % + /- 3.9 % vs 29.2 % + /- 3.7 % ) , and on intensive care unit arrival ( 35.2 % + /- 4.1 % vs 31.8 % + /- 3.5 % , P < .001 ) . Similarly , platelet count was higher in minimized circuit group on intensive care unit arrival , as was lowest platelet count recorded ( 170 x 10(3 ) + /- 48 cells/mm(3 ) vs 107 x 10(3 ) + /- 28 cells/mm(3 ) , P < .0001 ) . Time to extubation was shorter in minimized circuit group ( 848 + /- 737 minutes vs. 526 + /- 282 minutes , ( P < .01 ) , and total chest tube drainage was lower ( 1124 + /- 647 mL vs. 506 + /- 214 mL , P < .01 ) . Fewer red blood cells ( 148 vs 19 units ) were given in minimized circuit group ( P < .0001 ) . CONCLUSIONS A minimized cardiopulmonary bypass circuit provides less hemodilution , platelet consumption , chest tube output and lower post-operative blood loss than st and ard cardiopulmonary bypass . Red blood cell usage was also less . All differences are advantageous OBJECTIVE Closed circuit extracorporeal circulation ( CCECC ) has been developed to reduce deleterious effects of st and ard cardiopulmonary bypass ( CPB ) . This study compares the effects of CCECC ( CORx system ) , CPB , and off-pump coronary artery bypass grafting ( OPCAB ) on red blood cell damage , coagulation activation , fibrinolysis and cytokine expression . METHODS Thirty patients underwent coronary artery bypass grafting ( CABG ) . Twenty of them were r and omized into two groups : CCECC ( n = 10 ) , CPB ( n = 10 ) . While not r and omized , OPCAB ( n = 10 ) served as a separate reference group . CCECC and CPB patients received cardioplegic arrest . Interleukin 6 ( IL-6 ) , free hemoglobin ( fHb ) , von Willebr and factor activity ( vWf ) , thrombin-antithrombin-III-complex ( TATc ) , prothrombin fragment 1.2 ( F 1 + 2 ) and plasmin-antiplasmin complex ( PAPc ) were assessed preoperatively , perioperatively and 24 h postoperatively . RESULTS CCECC showed significantly lower red blood cell damage than CPB ( fHb : CCECC , 7.1+/- 5.7 micromol/l ; CPB , 16.8+/-11.4 micromol/l ; P = 0.025 ; OPCAB , 3.4+/-1.1 micromol/l ) . Perioperatively , CCECC exhibited significantly lower activation of coagulation and fibrinolysis than CPB , but did not differ from OPCAB ( vWf : CCECC , 133+/-52 % ; CPB , 241+/-128 % ; P = 0.052 ; OPCAB , 153+/-58 % ; TATc : CCECC , 4.7+/-0.9 ng/ml ; CPB , 31.1+/-15.8 ng/ml ; P < 0.001 ; OPCAB , 2.4+/-0.6 ng/ml ; PAPc : CCECC , 214+/-30 ng/ml ; CPB , 897+/-367 ng/ml ; P < 0.001 ; OPCAB , 253+/-98 ng/ml ) . In contrast , fibrinolysis markers and IL-6 were markedly increased in CCECC postoperatively ( PAPc : CCECC , 458+/-98 ng/ml ; CPB , 159+/-128 ng/ml ; P < 0.001 ; OPCAB , 262+/-174 ng/ml ; IL-6 : CCECC , 123.4+/-49.8 pg/dl ; CPB , 18.8+/-13.1 pg/dl ; P < 0.001 ; OPCAB , 31.6+/-26.2 pg/dl ) . CONCLUSIONS CCECC for CABG is associated with a significant reduction of red blood cell damage and activation of coagulation cascades similar to OPCAB when compared with conventional CPB while a delayed fibrinolytic and inflammatory activity was observed . These findings require further investigation to verify the promising concept of CCECC Since the establishment of miniaturized extracorporeal circulation ( mECC ) , there has been a great controversy about a possible increased risk of gaseous microembolism as compared to conventional extracorporeal circulation ( cECC ) . From March 2005 to June 2006 , a prospect i ve , r and omized study , comparing three different mECC ( MECC , PRECiSe , Resting Heart ) with a cECC ( HL30 Maquet ) was performed . Ninety-three patients undergoing elective bypass surgery were included . The amount and size of microbubbles during perfusion was detected in the arterial lines utilizing an ultrasound Doppler system . Clinical outcome was compared by evaluating the incidence of postoperative neuropsychological dysfunction , postoperative renal dysfunction and hospitalization as well as the 30-day mortality . The highest microbubble activity was measured in all devices during the first 10 minutes of extracorporeal circulation . The amount of microbubbles was lower in the Resting Heart system ( p = 0.01 ) , equal in the MECC system ( p = 0.16 ) and higher using the PRECiSe system as compared to the cECC ( p = 0.002 ) . The microbubble diameter did not differ between all groups ( p = 0.56 ) . Postoperative neuropsychological dysfunction ( p = 0.45 ) , renal dysfunction ( p = 0.67 ) , days of hospitalization ( p = 0.27 ) , and 30 day-mortality ( p = 0.30 ) did not differ between all groups . A great variability in the occurrence of gaseous microemboli depending on the applied circuit exists . The Resting Heart system has lower , the MECC system an equal and the PRECiSe system depicted a higher activity in comparison to a cECC . The hypothesis about an increased risk in mECC in comparison to cECC with regard to microbubble activity is not supported by our results We compared the inflammatory response , hemodilution , and blood loss in patients who underwent mini-cardiopulmonary bypass ( CPB ) or conventional CPB during coronary artery bypass grafting ( CABG ) . Ninety-eight consecutive patients with ischemic heart disease were r and omly assigned to mini-CPB ( n = 34 ) or conventional CPB ( n = 64 ) . Interleukin ( IL ) −8 and neutrophil elastase levels were measured before and after surgery . Hemodilution during CPB , blood loss during and after surgery were also evaluated . Compared with the conventional group , the mini-CPB group had lower levels of IL-8 on postoperative day 1 ( 8.3 ± 6.4 vs. 19 ± 11 pg/mL , p = 0.016 ) and of neutrophil elastase on postoperative days 1 ( 127 ± 52 vs. 240 ± 100 & mgr;g/L , p = 0.013 ) and 2 ( 107 ± 17 vs. 170 ± 45 & mgr;/L , p = 0.0001 ) . The mini-CPB group also has less blood loss during ( 620 ± 595 vs. 978 ± 658 mL , p = 0.012 ) and after the operation ( 578 ± 310 vs. 1,002 ± 651 mL , p = 0.0034 ) and a hemodilution ratio of 14 ± 2 vs. 25 % ± 3 % , p < 0.0001 . Thus , mini-CPB attenuated the inflammatory response and hemodilution , result ing in blood conservation in patients undergoing CABG BACKGROUND Drawbacks of conventional cardiopulmonary bypass ( CPB ) are increased inflammatory response , deteriorated coagulation and systemic organ dysfunction . A closed extracorporeal circuit ( CorX ) features reduced foreign surface area and priming volume . Potential benefits were studied in comparing the CorX system with conventional CPB in arrested heart coronary artery bypass grafting ( CABG ) . METHODS Two hundred and four patients were r and omly assigned either to CorX system ( n = 101 , group A ) or a st and ard CPB with cardiotomy reservoir ( n = 103 , group B ) . Besides evaluation of perioperative data and routine blood sample s , we focused on lung function and perioperative bleeding . Polymorphonuclear elastase ( PMNE ) and terminal complement complex ( TCC ) served to assess inflammatory response . RESULTS Patient demographics and operative data did not differ between groups . Postoperative lung function was not significantly impaired comparing groups A and B. Intraoperative blood loss was significantly higher in group A compared with group B ( 1245 + /- 947 mL vs 313 + /- 282 mL , p < 0.0001 ) as well as the need of fresh frozen plasma . Postoperative chest drainage did not differ significantly between groups . Two patients in each group required re-exploration due to bleeding . One hour after CPB , PMNE as well as TCC were significantly lower in group A compared with group B ( PMNE : 76 + /- 44 ng/mL vs 438 + /- 230 ng/mL , p < 0.0001 ; TCC : 16 + /- 8 IU/mL vs 29 + /- 19 IU/mL , p < 0.0001 ) . CONCLUSIONS The CorX system is safe and feasible in patients undergoing CABG . Despite of markedly reduced inflammatory reaction , no clinical benefit was observed Minimized extracorporeal circulation ( MECC , Maquet , Cardiopulmonary AG , Hirrlingen , Germany ) is an established procedure to perform coronary revascularization . Studies showed positive effects of MECC compared to conventional cardiopulmonary bypass ( CCPB ) procedures in terms of transfusion requirements , less inflammation reactions , and neurological impairments . Recent retrospective studies showed higher mean arterial pressure ( MAP ) and a lower frequency of vasoactive drug use . We addressed this issue in this study . The hypothesis was to find a higher MAP during coronary bypass grafting surgery in patients treated with MECC systems . We performed a prospect i ve , controlled , r and omized trial with 40 patients either assigned to MECC ( n = 18 ) or CCPB ( n = 22 ) undergoing coronary bypass grafting . Primary endpoints were the perioperative course of mean arterial pressure , and the consumption of norepinephrine . Secondary endpoints were the regional cerebral and renal oxygen saturation ( rSO2 ) as an indicator of area perfusion and the course of hematocrit . Clinical and demographic characteristics did not significantly differ between both groups . Thirty-day mortality was 0 % . At four of five time points during extracorporeal circulation ( ECC ) MAP values were significantly higher in the MECC group compared to CCPB patients ( after starting the ECC 60 + /- 11 mmHg vs. 49 + /- 10 mmHg , p = .002 ) . MECC patients received significantly less norepinephrine ( MECC 22.5 + /- 35 microg vs. CCPB 60.5 + /- 75 microg , p = .045 ) . The rSO2 measured at right and left forehead and the renal area was similar for both groups during ECC and significantly higher at CCPB group 1 and 4 hours after termination of CPB . Minimized extracorporeal circulation provides a higher mean arterial pressure during ECC and we found a lower consumption of vasoactive drugs in the MECC group . There was a decrease in regional tissue saturation at 1 and 4 hours post bypass in the MECC group possibly due to increased systemic inflammation and extravascular fluid shift in the CCPB group BACKGROUND Transient , sub clinical myocardial , renal , intestinal , and hepatic tissue injury and impaired homeostasis is detectable even in low-risk patients undergoing conventional cardiopulmonary bypass ( CPB ) . Small extracorporeal closed circuits with low priming volumes and optimized perfusion have been developed to reduce deleterious effects of CPB . METHODS A prospect i ve , r and omized trial was conducted in 49 patients undergoing elective coronary artery bypass graft surgery either with the use of a st and ard or mini-CPB system ( Synergy ) . We determined early postoperative inflammatory response ( leukocytosis , C-reactive protein , urine interleukin-6 ) , platelet consumption and activation ( urine thromboxane B2 ) , proximal renal tubular injury ( urine N-acetyl-glucosaminidase ) , and intestinal injury ( intestinal fatty acid binding protein ) . RESULTS In patients undergoing coronary artery bypass grafting with a mini-CPB system , we observed decreased priming volumes with subsequent attenuation of on-pump hemodilution , improved hemostatic status with reduced platelet consumption and platelet activation , decreased postoperative bleeding and minimized transfusion requirements . We also found reduced leukocytosis and decreased urinary interleukin-6 . Levels of urine N-acetyl-glucosaminidase were on average threefold lower , and urinary intestinal fatty acid binding protein was 40 % decreased in the patients on the mini-CPB system , as compared with st and ard CPB . CONCLUSIONS The use of the mini-CPB system during myocardial revascularization represents a viable nonpharmacologic strategy that can attenuate the alterations in the hemostatic system , reduce bleeding and transfusion requirements , decrease systemic inflammatory response , and reduce immediate postoperative renal and intestinal tissue injury OBJECTIVE Cardiopulmonary bypass ( CPB ) using a closed circuit system with minimal priming volume can be a solution to ameliorate adverse effects of CPB . We hypothesize that the use of mini-bypass in routine coronary artery bypass grafting ( CABG ) reduces homologous blood product use and postoperative bleeding . The study is design ed to determine the differences in blood loss and transfusion requirements associated with a minimized CPB circuit vs. a st and ard bypass circuit . METHODS From February 2009 to August 2009 , 80 patients were prospect ively r and omized to undergo elective CABG . Group A included 40 patients who had the minimized bypass circuit ( Medtronic Resting Heart Circuit ) . Group B had an equal number of patients who had the st and ard CPB circuit ( Stockert III , SEC.BM ) . Laboratory parameters for hemoglobin , hematocrit and platelet count were measured at baseline after initiation of CPB and after bypass . Blood usage was controlled by study -specific protocol ( transfusion for hemoglobin < 8 g/dl ) . Records were kept for blood products . The chest and mediastinal drainage was monitored for the first 24 postoperative hours . Ventilation time , inotropic use and intensive care unit ( ICU ) stay was compared in both groups . RESULTS There were no statistical differences in terms of patients ' demographics . Statistically significant differences were seen in transfused red blood cells volume ( 1.47±1.13 units in group A vs. 2.05±1.19 in group B , P<0.05 ) , fresh frozen plasma ( 2.5±1.62 unit vs. 3.55±2.58 units , P<0.001 ) , platelets ( 1.95±2.95 units vs. 3.23±2.85 ) , and postoperative drainage in 24 hours ( 531.62±220.12 ml vs. 729±294.9 ml , P<0.05 ) . The hematocrit was 33±5 % in group A , and 27±1 % in group B. There was statistical differences seen in the mean hemoglobin level which was 10.19±0.65 g/dl in group A , and 9.4±0.68 g/dl in group B. There was statistical difference in the duration of ventilation , length of ICU stay . The requirement of inotropic support was lower in group A. CONCLUSIONS The adoption of mini-bypass significantly reduces morbidity including donor blood usage and postoperative bleeding in routine CABG patients OBJECTIVES Although minimal extracorporeal circulation ( MECC ) and off-pump surgery are equal or better alternatives to conventional cardiopulmonary bypass ( CCPB ) regarding perioperative morbidity , use of blood and blood products and completeness of revascularization , CCPB is still being used in the majority of coronary artery bypass grafting ( CABG ) operations . METHODS AND RESULTS We investigated 1472 CABG operations in our center . A total of 1143 CABG operations were performed using CCPB , 220 using MECC and 109 were performed as off-pump coronary artery bypass ( OPCAB ) . All patients were recorded prospect ively . Perioperative follow-up was focused on the occurrence of arrhythmia , neurocognitive disorders and the need of blood and blood products . Operative mortality rates were comparable in all three groups . The mean number of distal anastomoses was 3.2+/-0.6 in the MECC group , 3.4+/-0.7 in the CCPB group and 1.9+/-0.8 in the OPCAB group ( P=0.01 ) . Arrhythmia occurred in 25 % of the MECC group and in 35.6 % of the CCPB group ( P=0.05 ) . Arrhythmia occurred in 21.7 % of the OPCAB group . Seven patients ( 3 % ) of the MECC group suffered neurocognitive disorders perioperatively compared to 74 ( 7 % ) patients of the CCPB group ( P=0.05 ) and three patients of the OPCAB group ( 3 % ) . The median number of blood transfusions per patient was 0.8 in the MECC group , 1.8 in the CCPB group and 0.8 in the OPCAB group ( P<0.0001 ) . CONCLUSIONS Perioperative morbidity of MECC and OPCAB is comparable to or even less in comparison to CCPB . MECC allows CABG surgery in cardiac arrest so that completeness of revascularization is being warranted and longer patency rates can be guaranteed . Furthermore , the use of blood and blood products is significantly less in MECC surgery so that MECC should be considered first choice in CABG surgery over CCPB and OPCAB We design ed a pilot study to assess as primary end point the safety and efficacy of a new phosphorylcholine-coated , closed cardiopulmonary bypass ( CPB ) system ( extracorporeal circulation , optimized [ ECC.O ] , Dideco , Mir and ola , Italy ) . The secondary end point was to compare results with two retrospectively matched cohorts of patients who underwent isolated coronary artery by-pass graft ( CAGB ) with nonphosphorylcholine-bonded circuits and cardiotomy suction ( Group II , n = 32 ) and off-pump coronary artery by-pass ( OPCAB ) ( Group III , n = 26 ) . In January 2005 , 30 patients ( Group I ) undergoing first-time CABG were assigned to the ECC.O group . Five minutes after CPB , initial hematocrit levels were significantly and consistently highest in Group I relative to Group II ( Group I , 29.7 + /- 4.4 vs. Group II , 22.7 + /- 4.1 ; P < 0.001 ) . Red blood cell transfusion rate was reduced drastically in Group I versus Group II ( P < 0.001 ) . High differences were also observed in C-reactive protein levels at 24 h after surgery ( Group I vs. Group II-P < 0.001 and vs. Group III-P < 0.001 ) and at 72-h peak value ( Group I vs. Group II-P < 0.001 and vs. Group III-P < 0.001 ) . The routine clinical use of the ECC.O system has been demonstrated to be both clinical ly safe and efficacious . An intensive training program for surgeons , perfusionists , and anesthesiologists is required Isolated aortic valve replacement ( AVR ) or coronary artery bypass grafting ( CABG ) using minimized extracorporeal circulation ( MECC ) has been shown to have less deleterious effects than st and ard cardiopulmonary bypass ( CPB ) . In this prospect i ve cohort study , we evaluated and compared clinical results of combined AVR with CABG using MECC . We prospect ively collected preoperative , intraoperative , postoperative and follow-up data of 65 patients who underwent combined AVR with CABG using MECC and compared these with 135 patients undergoing combined AVR with CABG using st and ard CPB . No significant differences were seen in patients demographic characteristics or intraoperative data . Patients in the MECC group experienced a smaller preoperative haemoglobin drop ( 4.5±0.8 g/dl vs. 5.0±0.5 g/dl , P=0.002 ) result ing in higher haemoglobin at discharge ( 11.3±1.3 g/dl vs. 10.8±1.1 g/dl , P=0.03 ) . They had decreased blood products requirements ( P=0.004 ) compared to patients in the st and ard CPB group . No differences were noted in pulmonary complications , neurological events or mortality . We present for the first time data showing that combined AVR with CABG using MECC is feasible and provides better clinical results compared to st and ard CPB with regard to blood products requirements , without compromising operative morbidity or mortality Since 2005 , we have used a novel technique based on the closed cardiopulmonary bypass system without cardiotomy suction ( minimal cardiopulmonary bypass [ mini-CPB ] ) for aortic valve replacement ( AVR ) . In this study , we investigated the clinical advantages of this approach . We prospect ively studied 32 patients who underwent isolated AVR using the mini-CPB ( group M , n = 13 ) or conventional CPB ( group C , n = 19 ) . We compared the hemodilution ratio , serum interleukin (IL)-6 and IL-8 levels , and blood transfusion volume between the two groups . The characteristics , duration of CPB , and aortic cross-clamping time did not differ between the two groups . The hemodilution ratio was significantly lower in group M just after starting CPB ( M vs. C : 14 % ± 2 % vs. 25 % ± 3 % , p = 0.0009 ) . IL-6 levels increased significantly after surgery in both groups , but the postoperative levels were significantly lower in group M at 6 ( 84.9 ± 24.9 pg/ml vs. 152 ± 78 pg/ml , p = 0.042 ) and 12 ( 72.7 ± 36.1 pg/ml vs. 123 ± 49.6 pg/ml , p = 0.029 ) hours after CPB . There were no differences in IL-8 or blood transfusion volume after CPB . Mini-CPB offers an alternative to conventional CPB for AVR and has some advantages regarding hemodilution and serum IL-6 levels . However , it is unlikely to become the st and ard approach for AVR because there are no marked clinical advantages of mini-CPB Objective Neurocognitive impairment can be a debilitating complication after cardiac surgery . The aim of this study was to assess the effect of minimal extracorporeal circulation ( MECC ) versus conventional extracorporeal circulation ( CECC ) on neurocognitive function after elective coronary artery bypass grafting ( CABG ) and whether this can be attributed to improved cerebral perfusion intraoperatively . Methods and results 64 patients scheduled for elective CABG surgery were prospect ively r and omly assigned to surgical revascularisation with MECC versus CECC . All patients were continuously monitored for changes in cerebral oxygenation with near-infrared spectroscopy during the procedure . Neurocognitive assessment was performed before surgery , on the day of discharge and at 3 months postoperatively using a battery of st and ardised neurocognitive tests . Both groups were comparable in terms of demographic and clinical data . MECC was associated with improved cerebral perfusion during cardiopulmonary bypass ( CPB ) . Eleven patients operated on with MECC and 17 with CECC experienced at least one episode of cerebral desaturation ( 38 % vs 55 % , p=0.04 ) with similar duration ( 10 vs 12.3 min , p=0.1 ) . At discharge patients operated on with MECC showed a significantly improved performance on complex scanning , visual tracking , focused attention and long-term memory . At 3 months significantly improved performance was also evident on visuospatial perception , executive function , verbal working memory and short-term memory . Patients operated on with MECC experienced a significantly lower risk of early cognitive decline both at discharge ( 41 % vs 65 % , p=0.03 ) and at 3-month evaluation ( 21 % vs 61 % , p<0.01 ) . Conclusions Use of MECC attenuates early postoperative neurocognitive impairment after coronary surgery compared with conventional CPB . This finding may have important implication s on the surgical management strategy for coronary artery disease . Clinical trial registration number The study is registered at Clinical Trials.gov , number NCT01213511 BACKGROUND Percutaneous coronary intervention ( PCI ) involving drug-eluting stents is increasingly used to treat complex coronary artery disease , although coronary-artery bypass grafting ( CABG ) has been the treatment of choice historically . Our trial compared PCI and CABG for treating patients with previously untreated three-vessel or left main coronary artery disease ( or both ) . METHODS We r and omly assigned 1800 patients with three-vessel or left main coronary artery disease to undergo CABG or PCI ( in a 1:1 ratio ) . For all these patients , the local cardiac surgeon and interventional cardiologist determined that equivalent anatomical revascularization could be achieved with either treatment . A noninferiority comparison of the two groups was performed for the primary end point -- a major adverse cardiac or cerebrovascular event ( i.e. , death from any cause , stroke , myocardial infa rct ion , or repeat revascularization ) during the 12-month period after r and omization . Patients for whom only one of the two treatment options would be beneficial , because of anatomical features or clinical conditions , were entered into a parallel , nested CABG or PCI registry . RESULTS Most of the preoperative characteristics were similar in the two groups . Rates of major adverse cardiac or cerebrovascular events at 12 months were significantly higher in the PCI group ( 17.8 % , vs. 12.4 % for CABG ; P=0.002 ) , in large part because of an increased rate of repeat revascularization ( 13.5 % vs. 5.9 % , P<0.001 ) ; as a result , the criterion for noninferiority was not met . At 12 months , the rates of death and myocardial infa rct ion were similar between the two groups ; stroke was significantly more likely to occur with CABG ( 2.2 % , vs. 0.6 % with PCI ; P=0.003 ) . CONCLUSIONS CABG remains the st and ard of care for patients with three-vessel or left main coronary artery disease , since the use of CABG , as compared with PCI , result ed in lower rates of the combined end point of major adverse cardiac or cerebrovascular events at 1 year . ( Clinical Trials.gov number , NCT00114972 . OBJECTIVE Cardiopulmonary bypass ( CPB ) is known to cause part of the systemic inflammatory reaction after cardiac surgery that can be responsible for organ failure . A novel technique based on a minimal extracorporeal circulation ( MECC(R ) ) system has been evaluated with regard to the inflammatory response in a prospect i ve study involving patients undergoing coronary artery bypass grafting . METHODS Sixty consecutive patients were r and omly assigned to either st and ard normothermic CPB ( n=30 ) or the MECC system , with a reduced priming volume , no aortic venting and no venous reservoir , excluding the blood-air interface ( n=30 ) . Specific evaluation of cytokine release ( IL-1beta , IL-6 , TNF-alpha ) , as well as neutrophil elastase secretion and beta-thromboglobulin release from platelets and S100 protein assay were performed . Serial blood sample s were taken prior to the onset , after initiation , at the end and after weaning of the CPB ; further sample s were collected 6 and 24h after the end of the CPB . RESULTS All patients were similar with regards to pre- and intra-operative characteristics and clinical outcomes were comparable for both groups . MECC system allowed a reduced hemodilution with a mean drop of the hematocrit of 8.5 vs. 15.3 % ( P<0.05 ) . Mononuclear phagocytes dropped in a more important manner under st and ard CPB conditions ( 247+/-151 vs. 419+/-168 , P=0.002 ) , but both groups demonstrated a rise in monocyte count at the end of the CBP . No significant release of IL-1beta was observed in either group . By the end of CPB , IL-6 levels were significantly lower in the MECC group ( 38.8+/-19.6 vs. 87.9+/-78.9 , P=0.04 ) , despite a higher monocyte count . Plasma levels of TNF-alpha rised significantly more during st and ard CPB than with the MECC system ( 17.8+/-15.4 vs. 10.1+/-5.6 , P=0.002 ) . With MECC , the neutrophil elastase release was reduced ( 72.7+/-47.9 vs. 219.6+/-103.4 , P=0.001 ) . Platelet count remained at higher values with the minimal compared to st and ard CPB . It is noteworthy to consider that beta-thromboglobulin levels showed slightly lower platelet activation in the MECC group at all times of CPB ( 110.5+/-55.6 vs. 134.7+/-46.8 , P=0.10 ) . The pattern of release of S100 protein showed higher values in patients undergoing st and ard CPB than after MECC . CONCLUSIONS The MECC system is suitable to maintain total extracorporeal circulation and demonstrates a lower inflammatory reaction when compared to st and ard CPB OBJECTIVE One of the complications of CPB is the systemic inflammatory response syndrome ( SIRS ) . Recent developments tend to minimize the biological impact of CPB in using miniaturized closed circuit with reduced priming volume and less blood-air interface . The benefit of these miniaturized closed circuits in terms of inflammatory response has been proved in coronary surgery . However , in open heart surgery , the CPB circuit is no more closed and the benefit of the miniaturized set-up could disappear . The aim of the study is to compare the SIRS between st and ard and miniaturized circuits in aortic surgery . METHODS Forty patients who underwent singular aortic valve replacement were r and omly assigned either to a st and ard CPB ( group A , n=20 ) or to a miniaturized CPB ( group B , n=20 ) . Pertinent clinical and surgical data were collected . Hematological parameters ( leukocyte and neutrophil counts ) and biochemical parameters ( C-reactive protein , cytokine tests ) were determined pre- , on and post-CPB . RESULTS There were an increase in leukocyte and neutrophil counts and a decline in hematocrit in both groups . In both groups , there was a raise after CPB , in C-reactive protein , IL-6 , TNF-alpha , neutrophil elastase , and IL-10 . However , the raises of elastase and TNF-alpha were significantly lower after the weaning of miniaturized CPB ( 116+/-46 ng/ml and 10+/-4 pg/ml , respectively ) compared to st and ard CPB ( 265+/-120 ng/ml , P=0.01 and 18+/-7 pg/ml , P=0.03 ) . The raise of IL-10 is also lower with miniaturized circuit ( 15+/-6 pg/ml ) compared to st and ard circuit ( 51+/-26 , P=0.004 ) . CONCLUSIONS This study demonstrates in aortic surgery , the lesser inflammatory response of a miniaturized CPB compared to a st and ard CPB . However , there is always some inflammation after CPB and a small bio-reactive free perfusion circuit is still to be found in open heart surgery During the last decade , minimized extracorporeal circulation ( MECC ) systems have shown beneficial effects to the patients over the conventional cardiopulmonary bypass ( CECC ) circuits . This is a prospect i ve r and omized study of 99 patients who underwent coronary artery bypass grafting ( CABG ) surgery , evaluating the postoperative haematological effects of these systems . Less haemodilution ( p=0.001 ) and markedly less haemolysis ( p<0.001 ) , as well as better preservation of the coagulation system integrity ( p=0.01 ) , favouring the MECC group , was found . As a clinical result , less bank blood requirements were noted and a quicker recovery , as far as mechanical ventilation support and ICU stay are concerned , was evident with the use of MECC systems . As a conclusion , minimized extracorporeal circulation systems may attenuate the adverse effects of conventional circuits on the haematological profile of patients undergoing CABG surgery OBJECTIVE This prospect i ve r and omized study sought to verify the systemic inflammatory response , inflammatory myocardial damage , and early clinical outcome in coronary surgery with the miniaturized extracorporeal circulation system or on the beating heart . METHODS Sixty consecutive patients were r and omized to miniaturized extracorporeal circulation ( n = 30 ) or off-pump coronary revascularization ( off-pump coronary artery bypass grafting , n = 30 ) . Intraoperative and postoperative data were recorded . Plasma levels of interleukin-6 and tumor necrosis factor-alpha were measured from systemic blood intraoperatively , at the end of operation , and 24 and 48 hours thereafter . Levels of the same markers and blood lactate were measured from coronary sinus blood intraoperatively to evaluate myocardial inflammation . Markers of myocardial damage were also analyzed . RESULTS One patient died in the off-pump coronary artery bypass grafting group . There was no statistical difference in early clinical outcome in both groups . Release of interleukin-6 was higher in the off-pump coronary artery bypass grafting group 24 hours after the operation ( P = .03 ) , whereas levels of tumor necrosis factor-alpha were not different in both groups . Cardiac release of interleukin-6 , tumor necrosis factor-alpha , and blood lactate were not different in both groups . Release of troponin T was not significantly different in both groups . Levels of creatine kinase mass were statistically higher in the miniaturized extracorporeal circulation group than in the off-pump coronary artery bypass grafting group , but only at the end of the operation ( P < .0001 ) . Hemoglobin levels were significantly higher in the miniaturized extracorporeal circulation group than in the off-pump coronary artery bypass grafting group after 24 hours ( P = .01 ) . CONCLUSION Miniaturized extracorporeal circulation can be considered similar to off-pump surgery in terms of systemic inflammatory response , myocardial inflammation and damage , and early outcome BACKGROUND We studied postoperative mortality and morbidity after coronary artery bypass graft surgery performed using the mini-extracorporeal circulation ( MECC ) system . METHODS From June 2001 to June 2002 , we r and omly enrolled 60 patients who underwent isolated elective coronary artery bypass graft surgery , and were operated on with the MECC system ( 30 patients : group A ) or st and ard cardiopulmonary bypass ( 30 patients : group B ) . Serial blood sample s were collected to evaluate the main preoperative , intraoperative , and postoperative clinical and biological variables ; and to measure hemolysis , interleukin-6 cytokine , and plasma C-reactive protein release . RESULTS A more stable hemoglobin level was detected in group A. The platelet count did not show a significant difference between the two groups . Interleukin-6 cytokine release showed higher values in group B , although no difference between groups was statistically significant . The time course of circulating plasma C-reactive protein concentration exhibited the same increase in both groups . Plasma free hemoglobin levels showed higher hemolysis peaks in group B , although a statistical significant difference was detected only at 4 hours after surgery . A higher cardiac index and reduced systemic and pulmonary vascular resistance index in the early postoperative period were found in group A at postoperative time 30 minutes . CONCLUSIONS Our experience shows that MECC offers satisfactory clinical benefits in terms of good hemodynamic support , safety , and low morbidity , although the study failed to demonstrate a significant clear superiority of MECC versus conventional cardiopulmonary bypass . The results need to be confirmed by a larger prospect i ve , r and omized study comparing MECC and st and ard cardiopulmonary bypass The st and ard heart-lung machine is deemed a major trigger of systemic inflammatory reactions , potentially inducing organ failure . The strict reduction of blood – artificial surface and blood-air contact might represent meaningful improvements of the extracorporeal technology with respect to organ preservation . In this study , we assessed perioperative myocardial damage by using a novel minimal extracorporeal circuit ( MECC ) and a conventional cardiopulmonary bypass ( CPB ) system . Sixty patients scheduled for coronary artery bypass surgery were r and omly assigned to either the MECC or the st and ard CPB system . Myocardial markers were determined by specific immunoassays 6 , 12 , and 24 hours after CPB initiation . Results were corrected for hemodilution . Demographics , hemodynamics , the number of anastomoses , CPB , and cross-clamp time were comparable between the groups . MECC patients demonstrated significantly lower levels of Troponin T ( ng/ml ) at 6 , 12 , and 24 hours ( 0.07 ± 0.01 vs. 0.16 ± 0.04 , p < 0.005 ; 0.12 ± 0.03 vs. 0.28 ± 0.08 , p < 0.008 ; 0.21 ± 0.05 vs. 0.35 ± 0.09 , p < 0.03 , respectively ) and creatine kinase-MB ( U/l ) at 6 and 12 hours ( 22.5 ± 1.5 vs. 40.6 ± 3.3 , p < 0.0001 ; 23.3 ± 3.4 vs. 40.8 ± 8.0 , p < 0.001 , respectively ) . Creatine kinase-MB at 24 hours tended to lower values in the MECC group but did not quite reach statistical significance . The MECC system may not only provide a less invasive solution to meet the requirements during cardiac surgery but also a more organ-preserving alternative to st and ard CPB BACKGROUND Cardiotomy suction and autotransfusion of mediastinal shed blood may contribute to the inflammatory response after cardiac surgery . We compared inflammatory activation , myocardial injury , bleeding , and hemoglobin levels in patients undergoing coronary surgery with or without retransfusion of cardiotomy suction blood and mediastinal shed blood . METHODS Twenty-nine patients were included in a prospect i ve r and omized study . Cardiotomy suction blood and mediastinal shed blood were either retransfused or discarded . Plasma concentrations of the cytokines tumor necrosis factor-alpha and interleukin-6 and complement factor C3a were measured preoperatively and 10 minutes , 2 hours , and 24 hours after cardiopulmonary bypass . C-reactive protein , erythrocyte sedimentation rate , troponin-T , and hemoglobin levels were analyzed preoperatively , and 24 and 48 hours after cardiopulmonary bypass . Postoperative bleeding the first 12 hours was registered . RESULTS Baseline data did not differ between the groups . Plasma concentrations of tumor necrosis factor-alpha , interleukin-6 , and C3a increased after surgery in both groups but significantly less in the group without cardiotomy suction and autotransfusion . The peak delta values in the no-retransfusion group was 36 % ( tumor necrosis factor-alpha ) , 47 % ( interleukin-6 ) , and 75 % ( C3a ) of the values in the retransfusion group . C-reactive protein , erythrocyte sedimentation rate , and troponin-T increased after surgery in both groups without intergroup differences . Postoperative bleeding and hemoglobin levels did not differ between the groups . No patient received homologous blood transfusion . CONCLUSIONS Coronary surgery without retransfusion of cardiotomy suction blood and mediastinal shed blood reduces the postoperative systemic inflammatory response BACKGROUND Coronary-artery bypass grafting ( CABG ) has traditionally been performed with the use of cardiopulmonary bypass ( on-pump CABG ) . CABG without cardiopulmonary bypass ( off-pump CABG ) might reduce the number of complications related to the heart-lung machine . METHODS We r and omly assigned 2203 patients scheduled for urgent or elective CABG to either on-pump or off-pump procedures . The primary short-term end point was a composite of death or complications ( reoperation , new mechanical support , cardiac arrest , coma , stroke , or renal failure ) before discharge or within 30 days after surgery . The primary long-term end point was a composite of death from any cause , a repeat revascularization procedure , or a nonfatal myocardial infa rct ion within 1 year after surgery . Secondary end points included the completeness of revascularization , graft patency at 1 year , neuropsychological outcomes , and the use of major re sources . RESULTS There was no significant difference between off-pump and on-pump CABG in the rate of the 30-day composite outcome ( 7.0 % and 5.6 % , respectively ; P=0.19 ) . The rate of the 1-year composite outcome was higher for off-pump than for on-pump CABG ( 9.9 % vs. 7.4 % , P=0.04 ) . The proportion of patients with fewer grafts completed than originally planned was higher with off-pump CABG than with on-pump CABG ( 17.8 % vs. 11.1 % , P<0.001 ) . Follow-up angiograms in 1371 patients who underwent 4093 grafts revealed that the overall rate of graft patency was lower in the off-pump group than in the on-pump group ( 82.6 % vs. 87.8 % , P<0.01 ) . There were no treatment-based differences in neuropsychological outcomes or short-term use of major re sources . CONCLUSIONS At 1 year of follow-up , patients in the off-pump group had worse composite outcomes and poorer graft patency than did patients in the on-pump group . No significant differences between the techniques were found in neuropsychological outcomes or use of major re sources . ( Clinical Trials.gov number , NCT00032630 . ) OBJECTIVE In an effort to minimize the effect of extracorporeal circulation ( ECC ) , mini-bypass is gaining clinical acceptance in routine coronary artery bypass grafting ( CABG ) . These small circuits target combine the clinical advantages of reduced prime , 100 % bio-coating and suction blood separation . We demonstrate that the use of mini-bypass in routine CABG reduces homologous blood product use and postoperative bleeding . Our goal was to also demonstrate that these small systems are effective in gaseous microemboli ( GME ) management as compared to a conventional extracorporeal system . METHODS Prospect i ve , r and omized study comparing 30 mini-bypass ( Dideco ECC.O ) to 30 conventional systems ( n=30 , Dideco 903 Avant ) . Study included CABG cases only , independent of preoperative coagulative status ; clinic ethical committee approval and informed patient consent was obtained before initiating study . RESULTS There were no statistical differences in terms of patient demographics . Statistically significant differences were seen in transfusion frequency ( 27 % of the study group vs 43 % in the control group , p=0.05 ) , transfused volume ( 133.3+/-244.5 ml vs 325+/-483.1 ml , p<0.05 ) , fresh frozen plasma ( 0 unit vs 3 units , p<0.001 ) , postoperative bleeding ( 301.8+/-531.9 ml vs 785.5+/-1000.4 ml , p<0.05 ) and GME activity post-arterial filter ( 0.14 microl vs 5.32 microl , p<0.05 ) . CONCLUSIONS The adoption of mini-bypass significantly potentially reduces hemodilution , donor blood usage , postoperative bleeding and exposure to GME in routine CABG patients as compared to the use of conventional extracorporeal circulation circuits BACKGROUND The present study was design ed to investigate whether use of left ventricular assisted technique ( LVA ) in beating-heart myocardial revascularization would exert less impact on patients ' inflammatory response , as compared with minimal extracorporeal circulation ( MECC ) . METHODS Seventy-three consecutive high-risk patients undergoing myocardial revascularization were r and omly assigned either to LVA ( group A ) or to MECC ( group B ) . Monocyte count and plasma concentration of C-reactive protein , inflammatory cytokines interleukin-1beta , interleukin-6 , and tumor necrosis factor-alpha , and polymorphonuclear elastase were measured at baseline and at various time points postoperatively . RESULTS Preoperative clinical and demographic data did not differ between the two groups . The two groups also were similar with respect to mortality , number of grafts performed , duration of extracorporeal circulation , and need for inotropes . However , LVA was associated with significantly less inflammatory response postoperatively compared with MECC , as indicated by a significant difference in interleukin-6 ( p = 0.002 ) , C-reactive protein ( p = 0.002 ) , monocyte percentage ( p = 0.006 ) , tumor necrosis factor-alpha ( p = 0.002 ) , and polymorphonuclear elastase ( p = 0.001 ) . CONCLUSIONS High-risk patients undergoing beating-heart myocardial revascularization with LVA show reduced inflammatory response compared with patients treated with the MECC The minimized extracorporeal circulation system ( MECC ) is being used to reduce priming volume and blood/polymer contact during cardiac procedures . In this study , we evaluated the efficacy and potential advantages of the system in coronary artery bypass graft ( CABG ) patients . We included two groups of patients destined for CABG in a prospect i ve , r and omized study : Group A was operated on the usual pump ( n = 30 ) while Group B was operated using the MECC ( n = 50 ) . Pre-operative demographics , intra-operative times and values as well as a series of post-operative outcome data ( blood loss , transfusion requirements , ventilation time , ICU and hospital stay ) were recorded . CK , CK-MB , troponin-T , IL-6 and IL-8 were measured . Pre-operative and post-operative lung function were assessed . In the MECC-operated group , patients developed less post-operative troponin-T ( 0.2 ± 0.3 vs. 0.5 ± 0.5 ng/mL , p=0.031 ) and less IL-8 ( 13.8 ± 5 vs. 22.5 ± 0.5 µg/L , p = 0.05 ) . While blood loss was comparable in both groups , packed red blood cells and fresh frozen plasma were given less frequently in the MECC group ( p = 0.015 resp . 0.022 ) . The one-tailed Student ’s t-test revealed shorter bypass time in the MECC group ( 74 ± 17 vs. 82 ± 24 min ) . There was no difference in ventilation and ICU-time ( patients were not treated in a fast-track fashion ) . The FEV1 was better in the MECC group ( relative values : 70.1 ± 18.2 % vs. 61.1 ± 12.3 % , p = 0.02 ) . Utilization of the MECC may cause less cytokine ( IL-8 ) liberation , owing to less blood/tubing contact , as well as less red blood cell and fresh frozen plasma dem and . It may also be the circuit in patients with chronic obstructive pulmonary disease ( COPD ) To evaluate the clinical results of aortic valve replacement performed with a miniaturized closed circuit extracorporeal circulation ( MECC ) system and to compare it to st and ard cardiopulmonary bypass ( CPB ) . One hundred and twenty consecutive patients undergoing isolated aortic valve replacement were r and omly assigned to either a miniaturized closed circuit CPB with the maquet-cardiopulmonary MECC System ( study group , n=60 ) or to a st and ard CPB ( control group , n=60 ) . Demographic characteristic and operative data were similar in the two groups . No hospital death occurred in either group and no difference in intensive care unit ( ICU ) stay and in-hospital stay was observed . Patients in the study group showed lower chest tube drainage ( 212+/-62 ml vs. 420+/-219 ml , P<0.05 ) and lower need for blood products ( 6.1 % vs. 40.4 % , P<0.05 ) than patients in the control group . Platelet count at ICU arrival was significantly higher in the study group ( 139+/-40 x 10(9)/l vs. 164+/-75 x 10(9)/l , P=0.05 ) . Peak postoperative troponin I release was significantly lower in the MECC group ( 3.81+/-2.7 ng/dl vs. 6.6+/-6.8 ng/dl , P<0.05 ) . In this r and omized study the MECC system has demonstrated best postoperative clinical results in terms of need for transfusion , platelets consumption and myocardial damage as compared to st and ard CPB |
1,636 | 28,301,692 | There is limited low- and very low- quality evidence currently on the effect of vitamin C supplementation and risk of CVD risk factors | BACKGROUND Vitamin C is an essential micronutrient and powerful antioxidant .
Observational studies have shown an inverse relationship between vitamin C intake and major cardiovascular events and cardiovascular disease ( CVD ) risk factors .
Results from clinical trials are less consistent .
OBJECTIVES To determine the effectiveness of vitamin C supplementation as a single supplement for the primary prevention of CVD . | Pathological formation of reactive oxygen species within the coronary circulation has been hypothesized to mediate some clinical manifestations of ischemic heart disease ( IHD ) by interfering with physiological regulation of coronary tone . To determine the degree to which coronary tone responds to acute changes in ambient levels of oxidants and antioxidants in vivo in a clinical setting , we measured the effect of an acute oxidative stress ( breathing 100 % oxygen ) on coronary capacitance artery diameter ( quantitative angiography ) and blood flow velocity through the coronary microcirculation ( intracoronary Doppler ultrasonography ) before and after treatment with the antioxidant vitamin C ( 3-g intravenous infusion ) in 12 IHD patients undergoing a clinical coronary interventional procedure . Relative to room air breathing , 100 % oxygen breathing promptly reduced coronary blood flow velocity by 20 % and increased coronary resistance by 23 % , without significantly changing the diameter of capacitance arteries . Vitamin C administration promptly restored coronary flow velocity and resistance to a slightly suprabasal level , and it prevented the reinduction of coronary constriction with rechallenge with 100 % oxygen . This suggests that acute oxidative stress produces prompt and substantial changes in coronary resistance and blood flow in a clinical setting in patients with IHD , and it suggests that these changes are mediated by vitamin C-quenchable substances acting on the coronary microcirculation . This observation may have relevance for clinical practice OBJECTIVES We sought to determine whether abnormal myocardial blood flow ( MBF ) responses to the cold pressor test ( CPT ) in patients with various risk factors may involve different mechanisms that could lead to varying responses of short- and long-term administration of antioxidants . BACKGROUND There is a growing body of evidence that increased vascular production of reactive oxygen species markedly reduces the bioavailability of endothelium-derived nitric oxide , leading to impaired vasodilator function . It is unknown whether increased oxidative stress is the prevalent mechanism underlying endothelial dysfunction in patients with different coronary risk factors . METHODS Fifty patients with normal coronary angiograms were studied . The MBF responses to CPT was determined by means of positron emission tomography before and after intravenous infusion of 3 g vitamin C or saline ( placebo ) , as well as after 3 months and 2 years of 2 g vitamin C or placebo supplementation daily . RESULTS In hypertensive patients , the change in MBF ( DeltaMBF ) was not modified significantly by short-term vitamin C administration challenges ( 0.20 + /- 0.20 ml/g/min ; p = NS ) but was significantly increased after three months and two years of treatment with vitamin C versus baseline ( 0.58 + /- 0.27 and 0.63 + /- 0.17 vs. 0.14 + /- 0.18 ml/g/min ; both p < or = 0.001 ) . In smokers , DeltaMBF in response to CPT was significantly increased after short-term vitamin C infusion and long-term vitamin C treatment ( 0.52 + /- 0.10 , 0.54 + /- 0.13 , 0.50 + /- 0.07 vs. -0.08 + /- 0.10 ml/g/min ; all p < or = 0.001 ) . In hypercholesterolemic patients , no improvement in DeltaMBF during CPT was observed after short- and long-term vitamin C treatment ( 0.05 + /- 0.14 , 0.08 + /- 0.18 , 0.02 + /- 0.19 vs. 0.08 + /- 0.16 ml/g/min ; p = NS ) . The CPT-induced DeltaMBF in hypertensive patients and smokers after follow-up was significant as compared with placebo and control subjects ( p < or = 0.001 ) . CONCLUSIONS The present study revealed marked heterogeneous responses in MBF changes to short- and long-term vitamin C treatment in patients with various risk factors , which highlights the quite complex nature underlying abnormal coronary vasomotion CONTEXT Basic research and observational studies suggest vitamin E or vitamin C may reduce the risk of cardiovascular disease . However , few long-term trials have evaluated men at initially low risk of cardiovascular disease , and no previous trial in men has examined vitamin C alone in the prevention of cardiovascular disease . OBJECTIVE To evaluate whether long-term vitamin E or vitamin C supplementation decreases the risk of major cardiovascular events among men . DESIGN , SETTING , AND PARTICIPANTS The Physicians ' Health Study II was a r and omized , double-blind , placebo-controlled factorial trial of vitamin E and vitamin C that began in 1997 and continued until its scheduled completion on August 31 , 2007 . There were 14,641 US male physicians enrolled , who were initially aged 50 years or older , including 754 men ( 5.1 % ) with prevalent cardiovascular disease at r and omization . INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily . MAIN OUTCOME MEASURES A composite end point of major cardiovascular events ( nonfatal myocardial infa rct ion , nonfatal stroke , and cardiovascular disease death ) . RESULTS During a mean follow-up of 8 years , there were 1245 confirmed major cardiovascular events . Compared with placebo , vitamin E had no effect on the incidence of major cardiovascular events ( both active and placebo vitamin E groups , 10.9 events per 1000 person-years ; hazard ratio [ HR ] , 1.01 [ 95 % confidence interval { CI } , 0.90 - 1.13 ] ; P = .86 ) , as well as total myocardial infa rct ion ( HR , 0.90 [ 95 % CI , 0.75 - 1.07 ] ; P = .22 ) , total stroke ( HR , 1.07 [ 95 % CI , 0.89 - 1.29 ] ; P = .45 ) , and cardiovascular mortality ( HR , 1.07 [ 95 % CI , 0.90 - 1.28 ] ; P = .43 ) . There also was no significant effect of vitamin C on major cardiovascular events ( active and placebo vitamin E groups , 10.8 and 10.9 events per 1000 person-years , respectively ; HR , 0.99 [ 95 % CI , 0.89 - 1.11 ] ; P = .91 ) , as well as total myocardial infa rct ion ( HR , 1.04 [ 95 % CI , 0.87 - 1.24 ] ; P = .65 ) , total stroke ( HR , 0.89 [ 95 % CI , 0.74 - 1.07 ] ; P = .21 ) , and cardiovascular mortality ( HR , 1.02 [ 95 % CI , 0.85 - 1.21 ] ; P = .86 ) . Neither vitamin E ( HR , 1.07 [ 95 % CI , 0.97 - 1.18 ] ; P = .15 ) nor vitamin C ( HR , 1.07 [ 95 % CI , 0.97 - 1.18 ] ; P = .16 ) had a significant effect on total mortality but vitamin E was associated with an increased risk of hemorrhagic stroke ( HR , 1.74 [ 95 % CI , 1.04 - 2.91 ] ; P = .04 ) . CONCLUSIONS In this large , long-term trial of male physicians , neither vitamin E nor vitamin C supplementation reduced the risk of major cardiovascular events . These data provide no support for the use of these supplements for the prevention of cardiovascular disease in middle-aged and older men . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00270647 One gram of ascorbic acid ( Vitamin C ) administered r and omly to a group of healthy young people ( aged 29 ± 5 years ) produced a significant mean fall in serum cholesterol of 16 per cent within two months . A similar supplement to a group of healthy older people ( aged 58 ± 3 years ) produced a significant mean fall in serum cholesterol of 14 per cent but required six to 12 months ' administration . Serial observations on a mixed age group of healthy people ( aged 38 ± 12 years ) over one calendar year revealed a seasonal fluctuation in serum cholesterol , the lowest levels being in summer ( June 5.5 ± 0.7 mmols/l ) and the highest levels in winter ( January 6.4 ± 0.8 mmols/l ) , a significant rise of 16 per cent . These changes showed an inverse relationship with the leucocyte and serum ascorbic acid levels which also revealed a seasonal fluctuation , the months April/September being higher than the months October/March . The administration of 1 g of ascorbic acid per day throughout the year abolished the winter rise in serum cholesterol levels . These results are discussed in the light of the relationship between cholesterol and vascular disease and the observations by Sir Richard Doll that lowering the cholesterol level , whether achieved by drugs or diet , results in a reduction in morbidity from myocardial infa rct ion Background —Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression , but the evidence from clinical trials is controversial . In the first 3 years of the ASAP trial , the supplementation with 136 IU of vitamin E plus 250 mg of slow-release vitamin C twice daily slowed down the progression of carotid atherosclerosis in men but not women . This article examines the 6-year effect of supplementation on common carotid artery ( CCA ) intima-media thickness ( IMT ) . Methods and Results —The subjects were 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years with serum cholesterol ≥5.0 mmol/L ( 193 mg/dL ) , 440 ( 84.6 % ) of whom completed the study . Atherosclerotic progression was assessed ultrasonographically . In covariance analysis in both sexes , supplementation reduced the main study outcome , the slope of mean CCA-IMT , by 26 % ( 95 % CI , 5 to 46 , P = 0.014 ) , in men by 33 % ( 95 % CI , 4 to 62 , P = 0.024 ) and in women by 14 % ( not significant ) . In both sexes combined , the average annual increase of the mean CCA-IMT was 0.014 mm in the unsupplemented and 0.010 mm in the supplemented group ( 25 % treatment effect , 95 % CI , 2 to 49 , P = 0.034 ) . In men , this treatment effect was 37 % ( 95 CI , 4 to 69 , P = 0.028 ) . The effect was larger in subjects with either low baseline plasma vitamin C levels or CCA plaques . Vitamin E had no effect on HDL cholesterol . Conclusions —These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons Background The grading of recommendation , assessment , development and evaluation ( GRADE ) approach is widely implemented in health technology assessment and guideline development organisations throughout the world . GRADE provides a transparent approach to reaching judgements about the quality of evidence on the effects of a health care intervention , but is complex and therefore challenging to apply in a consistent manner . Methods We developed a checklist to guide the research er to extract the data required to make a GRADE assessment . We applied the checklist to 29 meta-analyses of r and omised controlled trials on the effectiveness of health care interventions . Two review ers used the checklist for each paper and used these data to rate the quality of evidence for a particular outcome . Results For most ( 70 % ) checklist items , there was good agreement between review ers . The main problems were for items relating to indirectness where considerable judgement is required . Conclusions There was consistent agreement between review ers on most items in the checklist . The use of this checklist may be an aid to improving the consistency and reproducibility of GRADE assessment s , particularly for inexperienced users or in rapid review s without the re sources to conduct assessment s by two research ers independently OBJECTIVES To study the efficacy of vitamin E and C supplementation on the progression of carotid atherosclerosis , hypothesizing an enhanced preventive effect in men and in smokers and synergism between vitamins . DESIGN AND SUBJECTS Double-masked two-by-two factorial trial , r and omization in four strata ( by gender and smoking status ) to receive twice daily either 91 mg ( 136 IU ) of d-alpha-tocopherol , 250 mg of slow-release vitamin C , a combination of these or placebo for three years . A r and omized sample of 520 smoking and nonsmoking men and postmenopausal women aged 45 - 69 years with serum cholesterol > /= 5.0 mmol L-1 were studied . SETTING The population of the city of Kuopio in Eastern Finl and . INTERVENTION Twice daily either a special formulation of 91 mg of d-alpha-tocopherol , 250 mg of slow-release vitamin C , a combination of these ( CellaVie(R ) ) or placebo for three years . MEASUREMENTS Atherosclerotic progression , defined as the linear regression slope of ultrasonographically assessed common carotid artery mean intima-media thickness ( IMT ) , was calculated over semi-annual assessment s. RESULTS The average increase of the mean IMT was 0.020 mm year-1 amongst men r and omized to placebo and 0.018 mm year-1 in vitamin E , 0.017 mm year-1 in vitamin C and 0.011 mm year-1 in the vitamin combination group ( P = 0.008 for E + C vs. placebo ) . The respective means in women were 0.016 , 0.015 , 0.017 and 0.016 mm year-1 . The proportion of men with progression was reduced by 74 % ( 95 % CI 36 - 89 % , P = 0.003 ) by supplementation with the formulation containing both vitamins , as compared with placebo . CONCLUSIONS Our study shows that a combined supplementation with reasonable doses of both vitamin E and slow-release vitamin C can retard the progression of common carotid atherosclerosis in men . This may imply benefits with regard to other atherosclerosis-based events BACKGROUND There is evidence for increased formation of free radicals in patients with hypertension , raising the possibility that NO is inactivated by free radicals , which impairs coronary endothelial function . Therefore , we tested the hypothesis that the antioxidant vitamin C could improve abnormal endothelial function of coronary arteries in patients with hypertension . METHODS AND RESULTS In 22 hypertensive patients without relevant coronary artery stenoses , endothelium-dependent vascular responses of the left anterior descending coronary artery ( LAD ) to acetylcholine ( 0.01 , 0.1 , and 1.0 micromol/L ) were determined before and immediately after intravenous infusion of 3 g vitamin C ( 17 patients ) or placebo ( 5 patients ) . In a subgroup of 10 patients , papaverine-induced flow-dependent vasodilation ( FDD ) was measured before and after vitamin C ( 5 patients ) or placebo ( 5 patients ) infusion . Segmental responses of the coronary artery luminal area were analyzed with quantitative coronary angiography . Before vitamin C infusion , the mean changes of LAD luminal areas at increasing doses of acetylcholine were -6.1+/-2.2 % , -15.2+/-4.9 % , and -33.9+/-8.1 % ( negative numbers symbolize vasoconstriction ) and during FDD , 5.4+/-1.0 % . The vasoconstrictor response during acetylcholine was reduced and FDD was augmented by vitamin C. After vitamin C infusion , LAD luminal areas changed by -3.2+/-2.3 % , -5.8+/-3.6 % , and -10.2+/-5.6 % ( P<.05 , acetylcholine ) and 17.8+/-2.8 % ( P<.05 , FDD ) . Doppler flow velocity ( during baseline , acetylcholine , and FDD ) was not significantly affected by vitamin C. CONCLUSIONS Vitamin C improves the endothelium-dependent vasomotor capacity of coronary arteries in patients with hypertension and patent coronary arteries . These findings suggest that increased oxidative stress contributes to endothelial dysfunction in hypertensive patients BACKGROUND Control of hyperlipidemia is vital in patients with cardiovascular disease ( CVD ) . Omega-3 fatty acids ( n-3FAs ) have desirable effects on serum triglyceride ( TG ) levels , thrombosis , and arrhythmia , but lead to increases in serum low-density lipoprotein ( LDL ) and apo-B as well . OBJECTIVE To determine and compare the effects of administration of n-3FAs , vitamin C ( VitC ) and n-3FAs + VitC on the serum levels of LDL , apoB , other serum lipids , and malondialdehyde ( MDA ) . The present study was performed in Tehran University of Medical Sciences from 2000 to 2001 . DESIGN In a double-blind , placebo trial of parallel design , 68 hyperlipidemic patients [ total cholesterol ( TC ) and TG greater than 200 mg/dL ] were r and omly assigned to receive daily 500 mg VitC , 1 g n-3FAs , 500 mg VitC + 1 g n-3FAs , or placebo ( control ) for 10 weeks . Fasting blood sample s were collected at the beginning and at the end of the period . TG , TC , LDL-cholesterol-C ( LDL-C ) , and high-density lipoprotein-cholesterol ( HDL-C ) were measured enzymatically , VitC and MDA colorimetrically , and apo-B and apo-A-I immunoturbidometrically . The pattern of food consumption , socio-economic , and anthropometric indices were determined ; there was no significant change in these indices during the study . RESULTS There was a significant difference in the blood VitC level at the end of the study in comparison to the initial value in the VitC ( p = 0.001 ) and VitC + n-3FAs ( p = 0.027 ) groups . Similarly , the serum TG level at the end of study was significantly different from the initial value in the n-3FAs group ( p = 0.002 ) and also from the final value in the control group ( p = 0.013 ) . In the VitC group , there was a significant decrease in TC ( p = 0.004 ) , apo-B ( p = 0.005 ) , and MDA ( p = 0.015 ) at the end of study as compared to the respective initial values . There was also a significant increase in blood VitC compared to the control value ( p = 0.018 ) and a significant decrease in MDA compared to the n-3FAs group ( p = 0.034 ) . At the end of study , in the n-3FAs group , there was a significant ( p = 0.04 ) and a marginally significant decrease ( p = 0.05 ) , respectively , in TG/HDL and apo-B levels as compared to the initial values , and the TG/HDL ratio showed a significant decrease as compared to the control group ( p = 0.047 ) . CONCLUSION Simultaneous administration of n-3FAs and VitC had no beneficial effects on the lipid profile of hyperlipidemic patients , but 1 g purified n-3FAs daily for 10 weeks is a beneficial supplement for decreasing TG without any increase in LDL-C , apo-B or MDA . Administration of 500 mg VitC for more than 10 weeks might decrease significantly TC and apo-B in hyperlipidemic patients Monocyte recruitment and retention in the vasculature is influenced by oxidative stress and is involved in cardiovascular disease ( CVD ) . Individuals with low plasma ascorbate are at elevated risk of CVD . It is unknown whether vitamin C supplementation affects monocyte adhesion to endothelial cells ( ECs ) in healthy non-smokers . In a r and omised double-blind crossover study the effect of vitamin C supplementation ( six weeks , 250 mg/day ) was determined in subjects with normal ( HIC ) and below average ( LOC ) plasma vitamin C concentration at baseline ( mean=67 microM , n=20 , mean=32 microM , n=20 , respectively ) . LOC subjects showed 30 % greater monocyte adhesion to ECs . This was significantly reduced by 37 % ( P<0.02 ) following vitamin C supplementation to levels of HIC monocyte adhesion . No differences in plasma malondialdehyde concentrations were observed between groups or after supplementation . In conclusion , vitamin C supplementation normalises monocyte adhesion in subjects with low plasma vitamin C ( LOC ) . This process may be related to a direct effect on monocytes , independent of lipid peroxidation There is mounting evidence that antioxidants may help to prevent coronary heart disease and modulate some thrombotic events such a platelet adhesion . However , the effects of antioxidant supplementation on platelet function in vivo are controversial . A double-blind , r and omised , placebo-controlled study was performed on 40 healthy volunteers ( 20 - 50 years ) supplemented daily with vitamin E ( 300 mg ) , vitamin C ( 250 mg ) or beta-carotene ( 15 mg ) for 8 weeks . Platelet function was assessed by platelet aggregation induced by ADP , arachidonic acid or collagen , platelet responsiveness to the inhibitor PGE1 , beta-thromboglobulin release and ATP secretion . Supplementation with vitamin E result ed in a significant increase in platelet alpha-tocopherol level ( + 68 % ) reflecting closely the increase in plasma alpha-tocopherol level ( + 69 % ) . Platelet function was significantly decreased by vitamin E as revealed by the decreased platelet aggregation in response to ADP and arachidonic acid , the increased sensitivity to inhibition by PGE1 , the decreased plasma beta-thromboglobulin concentration and the decreased ATP secretion . Supplementation with vitamin C did not affect platelet function significantly although a trend towards a decreased platelet aggregability and an increased sensitivity to the inhibitor PGE1 were observed . No significant changes in platelet function occurred after supplementation with beta-carotene . In conclusion , supplementation of healthy volunteers with vitamin E decreased platelet function whereas supplementation with vitamin C or beta-carotene had no significant effects Numerous observational studies showed associations of antioxidants ( vitamins C and E ) and folate intake with a reduced risk of cardiovascular disease , but r and omized controlled clinical trials have generally not supported this hypothesis . The objective of this study was to investigate the effects of a daily dosage of 1000 mg vitamin C , 800 mg vitamin E , and 10 mg folate on markers of vascular function in 31 young healthy male adults . Cardiovascular values after a 12-week vitamin ( 14 subjects ) or placebo ( 17 subjects ) intervention were compared to baseline values . Cardiovascular parameters ( blood pressure , stroke volume , heart rate , cardiac output , vascular resistance , arterial compliance ) were measured continuously after an overnight fast under controlled circumstances with a Finometer device . Our main finding was a significant decrease ( p = 0.03 ) in systolic blood pressure in the experimental group . No statistically significant changes were observed within other cardiovascular variables of the experimental group , but possible beneficial decreases in diastolic blood pressure and increases in arterial compliance after 12 weeks of vitamin supplementation were indicated . In conclusion , beneficial effects of antioxidants and folate were observed probably because the supplementation was used by young healthy subjects under carefully controlled conditions The aim of this investigation is to study the hypothesis that vitamin C has beneficial effects on some risk factors of cardiovascular diseases . Sixty-seven volunteers participated in this study . Thirty and thirty-seven subjects were assigned r and omly to two groups . The first was given a placebo and the second was given a vitamin C , respectively . Both regimens were followed for six months . The dose of vitamin C was 500 mg/day . Double blind technique was used throughout the study . These data supported part of the beneficial effects of vitamin C on atherosclerosis process , i.e. reduce significantly body fat , systolic blood pressure , and pulse , and increase significantly high density lipoprotein . On the other h and , these data did not show favourable effects on other lipid parameters , i.e. cholesterol , triglyceride , low density lipoprotein , and very low density lipoprotein OBJECTIVE To examine the relation of serum ascorbic acid level to serum lipid and lipoprotein levels among a r and om sample of the US adult population . METHODS Using linear regression , the relation of serum ascorbic acid level to serum lipid and lipoprotein levels was examined among 5,412 women and 5,116 men enrolled in the Second National Health and Nutrition Examination Survey ( NHANES II ) , 1976 - 1980 . Age , race , body mass index , level of physical activity , level of education , alcohol intake , and dietary energy , cholesterol , and fat intakes , and other potential confounders were included in the multivariate models . RESULTS Serum ascorbic acid level was independently associated with high-density lipoprotein cholesterol ( HDL-C ) among women ; each 1 mg/dl increase in serum ascorbic acid level ( range 0.1 to 2.7 mg/dl ) was associated with a 2 mg/dl increase in HDL-C level ( p = 0.001 ) . Because other investigators have demonstrated an inverse relation between ascorbic acid intake or blood levels and total serum cholesterol in individuals with elevated total serum cholesterol levels , we analyzed four subgroups of NHANES II participants with total serum cholesterol levels > 200 mg/dl . Among women with total serum cholesterol levels > or = 200 mg/dl , each 1 mg/dl increase in serum ascorbic acid level was independently associated with an increase of 2 to 3 mg/dl in HDL-C level ( p < or = 0.05 ) . Serum ascorbic acid level was not significantly associated with other serum lipids or lipoproteins . CONCLUSIONS If the observed associations are linked causally , they would suggest that ascorbic acid is a factor in cholesterol homeostasis among women and may be particularly important for women at increased risk for coronary heart disease BACKGROUND R and omized trials have largely failed to support an effect of antioxidant vitamins on the risk of cardiovascular disease ( CVD ) . Few trials have examined interactions among antioxidants , and , to our knowledge , no previous trial has examined the individual effect of ascorbic acid ( vitamin C ) on CVD . METHODS The Women 's Antioxidant Cardiovascular Study tested the effects of ascorbic acid ( 500 mg/d ) , vitamin E ( 600 IU every other day ) , and beta carotene ( 50 mg every other day ) on the combined outcome of myocardial infa rct ion , stroke , coronary revascularization , or CVD death among 8171 female health professionals at increased risk in a 2 x 2 x 2 factorial design . Participants were 40 years or older with a history of CVD or 3 or more CVD risk factors and were followed up for a mean duration of 9.4 years , from 1995 - 1996 to 2005 . RESULTS A total of 1450 women experienced 1 or more CVD outcomes . There was no overall effect of ascorbic acid ( relative risk [ RR ] , 1.02 ; 95 % CI , 0.92 - 1.13 [ P = .71 ] ) , vitamin E ( RR , 0.94 ; 95 % CI , 0.85 - 1.04 [ P = .23 ] ) , or beta carotene ( RR , 1.02 ; 95 % CI , 0.92 - 1.13 [ P = .71 ] ) on the primary combined end point or on the individual secondary outcomes of myocardial infa rct ion , stroke , coronary revascularization , or CVD death . A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior CVD ( RR , 0.89 ; 95 % CI , 0.79 - 1.00 [ P = .04 ] ; P value for interaction , .07 ) . There were no significant interactions between agents for the primary end point , but those r and omized to both active ascorbic acid and vitamin E experienced fewer strokes ( P value for interaction , .03 ) . CONCLUSION There were no overall effects of ascorbic acid , vitamin E , or beta carotene on cardiovascular events among women at high risk for CVD The purpose of this study was to investigate the impact of ascorbic acid ( AA ) consumption on the oxidative stress status of untrained volunteers participating in a supervised exercise program . The study included 46 young adults ( average age , 23.5 ± 0.59 years ; 37 females , 9 males ) who remained sedentary ( n = 16 ) or participated in 30 min of outdoor aerobic running ( n = 30 ) at an intensity corresponding to 65%-75 % of maximum heart rate for 3 times per week for 12 weeks . Exercised subjects were r and omly assigned to an exercise group without AA supplementation ( control ; n = 10 ) or received either 250 mg ( n = 10 ) or 500 mg ( n = 10 ) of AA supplementation previous to each exercise session . Blood sample s were taken on day 0 and day 84 to evaluate metabolic profiles and antioxidant status . Sedentary subjects underwent in a single bout of aerobic running to determine total antioxidant status ( TAS ) and malondiadehyde ( MDA ) at pre- and postexercise with or without AA supplementation . No significant change in TAS was observed . Plasma MDA significantly increased at postexercise ( P < 0.05 ) , and AA supplementation decreased MDA level significantly ( P < 0.05 ) . After 3 months of exercise , there was no significant change in blood glucose , lipid profile , MDA , TAS , superoxide dismutase ( SOD ) , glutathione peroxidase ( GPx ) , and catalase activities amongst groups . Supplementation of AA was associated with minor and inconsistent reductions in SOD , GPx , and catalase activities ( P < 0.05 ) . These findings indicate that pre-exercise supplementation of ascorbic acid does not alter oxidative stress markers in the plasma and erythrocytes of young adults engaged in a supervised exercise program The aim of the study was to establish whether it is possible , in a group of deliberately selected subjects with hyperlipidaemia , to modulate cholesterol levels by ascorbic acid administered at a dose of 500 mg/day . The authors assessed the levels of vitamin C , total and HDL cholesterol , triacylglycerols in the blood serum of 140 prob and s assigned to an 83-member experimental group , and to a 57-member control group . The experimental group was provided Celaskon effervescens Spofa at a dose of 500 mg/day/person . The experiment lasted for 18 months . Blood collection s were made in the whole cohort at six-month intervals . Administration of L-ascorbic acid led to a highly significant decrease in the levels of total and LDL cholesterol . After 12 months of study , a highly significant decrease in atherogenic index and an increase in HDL cholesterol levels were found persisting until the end of the experiment Plasma ascorbic acid ( AA ) frequently is positively correlated with high-density-lipoprotein ( HDL ) cholesterol and inversely related to total cholesterol concentration . To determine if vitamin C intake can alter cholesterol concentration , we examined the effect of vitamin C supplementation ( 1 g/d ) on lipoprotein cholesterol and triglyceride levels in 138 subjects , aged 20 to 65 years , who completed an 8-month r and omized , double-blinded , placebo-controlled trial . Individuals with higher levels of plasma AA ( > 80 mumol/L for men and > 90 mumol/L for women ) , HDL cholesterol ( > 1.4 mmol/L for men and > 1.7 mmol/L for women ) , and total cholesterol ( > 6.7 mmol/L ) were excluded from this trial . We observed no overall effect of supplementation on plasma concentrations of HDL , LDL , or total cholesterol , apolipoprotein ( apo ) B , or triglyceride . We did observe a marginally significant ( P < 0.10 ) increase of 1.9 mumol/L ( 5.3 mg/dL ) in apo A-I concentration with supplementation and a significant ( P < 0.05 ) difference of 0.10 mmol/L ( 3.8 mg/dL ) in HDL cholesterol concentration between vitamin C and placebo treatment in a nonr and omized subgroup of individuals ( n = 43 ) and a baseline plasma AA level less than 55 mumol/L. Although the apo A-I concentration increase was only marginally significant with supplementation , change in plasma AA concentration was significantly ( P < 0.05 ) correlated with change in apo A-I concentration in the entire sample . The overall results of this trial were negative , but our data do not allow us to rule out the possibility that vitamin C supplementation might increase HDL cholesterol or apo A-I concentrations among individuals with lower plasma AA levels Regulation of monocyte adhesion molecule gene expression is via redox sensitive transcription factors . We have investigated whether dietary antioxidant supplementation with vitamin C ( 250 mg/day ) can modulate monocyte ICAM-1 expression in healthy male subjects with low plasma vitamin C at baseline . In a r and omised , double-blind , crossover study , monocyte ICAM-1 mRNA was analysed using quantitative reverse transcriptase PCR . Protein was determined by flow cytometry ( monocytes ) and ELISA ( plasma ) . Monocyte numbers were unaltered by supplementation . Subjects with low plasma vitamin C ( < 50 microM ) prior to supplementation expressed higher levels of monocyte ICAM-1mRNA , and showed a significant ( 50 % ) reduction in ICAM-1mRNA expression after 6 weeks of 250 mg/day vitamin C supplementation ( p<0.05 ) . This was paralleled by a reduction in sICAM-1 ( p<0.05 ) . For the first time , these results show that dietary vitamin C can modulate monocyte ICAM-1 gene expression in vivo , where regulation of gene expression represents a novel mechanism for benefit from dietary antioxidants BACKGROUND The evidence for a potential benefit of antioxidant vitamins and folic acid in cardiovascular disease ( CVD ) prevention is derived from laboratory , clinical , and observational epidemiological studies but remains inconclusive . Large-scale r and omized trials with clinical end points are necessary to minimize confounding and provide unbiased estimates of the balance of benefits and risks , yet data from such trials are scarce , especially among women . METHODS The Women 's Antioxidant Cardiovascular Study ( WACS ) is a r and omized , double-blind , placebo-controlled trial testing whether antioxidant vitamins and a folic acid/vitamin B(6)/vitamin B(12 ) combination prevent future cardiovascular events among women with preexisting CVD or > or=3 CVD risk factors . This paper describes the design of the trial and baseline characteristics of participants , evaluates the success of r and omization , and addresses the generalizability of future findings . RESULTS In a factorial design , 8171 U.S. female health professionals aged > or=40 years were r and omized to vitamin E , vitamin C , beta-carotene , or placebos . Of these women , 5442 were also subsequently r and omized to folic acid/vitamin B(6)/vitamin B(12 ) or placebo . The r and omization was successful , as evidence d by similar distributions of baseline demographic , health , and behavioral characteristics across treatment groups . The clinical profile of participants was similar to that observed in another large trial of women with CVD . CONCLUSIONS The similar distribution of known potential confounders across treatment groups provides reassurance that unmeasured or unknown potential confounders are also equally distributed . Although a definitive conclusion regarding generalizability requires additional trials in diverse population s , there is little biological basis for supposing that the benefit-risk balance differs in other high-risk women In patients with intermittent claudication , exercise is associated with a marked increase in oxidative stress , likely responsible for systemic endothelial perturbation . In 31 claudicant patients , we assessed the effect of vitamin C administration on the acute changes induced by maximal and submaximal exercise in endothelium-dependent , flow-mediated dilation ( FMD ) , and in plasma levels of thiobarbituric acid-reactive substances ( TBARS ) and soluble intercellular adhesion molecule-1 ( sICAM-1 ) . In 16 claudicants , maximal exercise reduced FMD ( from 8.5+/-0.9 to 3.7+/-0.8 % , P<0.01 ) , and increased plasma levels of TBARS ( from 1.93+/-0.06 to 2.22+/-0.1 nmol/ml , P<0.02 ) and of sICAM-1 ( from 282+/-17 to 323+/-19 ng/ml , P<0.01 ) . In eight of these patients , r and omized to vitamin C , exercise-induced changes in FMD and biochemistry were abolished . This beneficial effect was not observed in the eight patients r and omized to saline . In 15 patients , who walked until the onset of claudication pain ( submaximal exercise ) , and in ten control subjects , who performed maximal exercise , no changes were observed with exercise . Thus , in claudicants , vitamin C prevents the acute , systemic impairment in endothelial function induced by maximal exercise . This finding provides a rationale for trials investigating antioxidant therapy and cardiovascular risk in patients with intermittent claudication Serum lipid and uric acid levels were investigated in two groups of healthy young students . Each member of the control group was given 1 g of citric acid , and each member of the experimental group 4 g of L-ascorbic aicd daily for 4 months . Blood sample s were drawn every month and leucocyte ascorbic acid , serum ascorbic acid , cholesterol , free fatty acids , triglycerides and uric acid were determined . The ascorbic acid did not cause dramatic changes in lipid parameters , and no evidence could be found that ascorbic acid raises serum uric acid levels Objectives To determine the effect of oral vitamin C supplements on ambulatory blood pressure and plasma lipids . Design A 6-month double-blind r and omized placebo-controlled cross-over study with a 1-week washout between cross-over periods . Methods Vitamin C 500 mg daily or matching placebo was given to 40 men and women aged between 60 and 80 years for 3 months each in a cross-over fashion . Clinic and 24-h ambulatory blood pressure , plasma ascorbate and lipids were measured at baseline and at the end of each cross-over phase . Results Clinic blood pressure did not change between placebo and vitamin C phases . Daytime ambulatory blood pressure showed a small but significant fall in systolic blood pressure ( 2.0 ± 5.2 mmHg ; 95 % confidence interval 0–3.9 mmHg ) but not in diastolic blood pressure . Regression analysis showed that with increasing baseline daytime blood pressure the fall in blood pressure with vitamin C supplementation increased . Regression analysis of the change in high-density lipoprotein ( HDL ) cholesterol showed a significant effect of sex on the change in HDL cholesterol . In women , but not men , HDL cholesterol increased significantly by 0.08 ± 0.11 mmol/l , P = 0.007 . There was no change in low-density lipoprotein cholesterol between treatment periods . Conclusion In older adults high intakes of ascorbic acid have modest effects on lowering high systolic blood pressure , which could contribute to the reported association between higher vitamin C intake and lower risk of cardiovascular disease and stroke We have investigated the effect on blood pressure of treatment with vitamin C ( an antioxidant and free radical scavenger ) in patients with both systolic and essential hypertension . Following a 2-week run-in phase , two age- and sex-matched groups of untreated hypertensive subjects were r and omised in a double-blind study to receive 6 weeks ' oral treatment with either vitamin C , 250 mg twice daily ( n = 22 ; 8M/14F , mean age 73.7 + /- 4.9 years ) or placebo , one capsule twice daily ( n = 26 ; 10M/16F , mean age 73.8 + /- 5.3 years ) . Blood pressure was measured in the sitting position using a r and om zero sphygmomanometer on three occasions during the run-in phase , and again at 2 , 4 and 6 weeks after commencing treatment . Venous blood sample s for measurement of plasma ascorbic acid ( AA ) and lipid peroxides ( LP ) were measured in all subjects at baseline and at 4 and 6 weeks after the start of vitamin C or placebo treatment . During the study period , significant falls in both systolic ( vitamin C group , mean change -10.3 ( 95 % CI 0.7 - 20.0 ) mm Hg , p = 0.05 ) and diastolic ( vitamin C group , mean change -5.9 ( 95 % CI 0.2 - 11.5 ) mm Hg , p = 0.03 ; placebo group , mean change -4.7 ( 95 % CI 0.3 - 9.1 ) mm Hg , p = 0.05 ) blood pressure occurred . However , no statistical difference between the effects of either treatment on blood pressure was observed . At baseline , AA concentrations were lower in the vitamin C-treated group compared with the placebo group ( 44.6 + /- 2.4 vs. 57.7 + /- 4.2 mumol/l , p < 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS |
1,637 | 28,604,117 | Overall , there is a growing body of evidence for post-docetaxel treatment options available in patients with mCRPC . | OBJECTIVE Prostate cancer is a highly prevalent form of cancer in older men and is one of the leading causes of death from cancer in men across the globe .
Many therapeutic agents have been approved for patients with metastatic castration-resistant prostate cancer ( mCRPC ) , particularly as a post-docetaxel treatment strategy .
The objective of this systematic literature review was to assess published efficacy and safety data for select mCRPC therapies - such as abiraterone , cabazitaxel , and enzalutamide - in the post-docetaxel setting . | BACKGROUND Enzalutamide ( formerly called MDV3100 ) targets multiple steps in the and rogen-receptor-signaling pathway , the major driver of prostate-cancer growth . We aim ed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy . METHODS In our phase 3 , double-blind , placebo-controlled trial , we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity . We r and omly assigned them , in a 2:1 ratio , to receive oral enzalutamide at a dose of 160 mg per day ( 800 patients ) or placebo ( 399 patients ) . The primary end point was overall survival . RESULTS The study was stopped after a planned interim analysis at the time of 520 deaths . The median overall survival was 18.4 months ( 95 % confidence interval [ CI ] , 17.3 to not yet reached ) in the enzalutamide group versus 13.6 months ( 95 % CI , 11.3 to 15.8 ) in the placebo group ( hazard ratio for death in the enzalutamide group , 0.63 ; 95 % CI , 0.53 to 0.75 ; P<0.001 ) . The superiority of enzalutamide over placebo was shown with respect to all secondary end points : the proportion of patients with a reduction in the prostate-specific antigen ( PSA ) level by 50 % or more ( 54 % vs. 2 % , P<0.001 ) , the soft-tissue response rate ( 29 % vs. 4 % , P<0.001 ) , the quality -of-life response rate ( 43 % vs. 18 % , P<0.001 ) , the time to PSA progression ( 8.3 vs. 3.0 months ; hazard ratio , 0.25 ; P<0.001 ) , radiographic progression-free survival ( 8.3 vs. 2.9 months ; hazard ratio , 0.40 ; P<0.001 ) , and the time to the first skeletal-related event ( 16.7 vs. 13.3 months ; hazard ratio , 0.69 ; P<0.001 ) . Rates of fatigue , diarrhea , and hot flashes were higher in the enzalutamide group . Seizures were reported in five patients ( 0.6 % ) receiving enzalutamide . CONCLUSIONS Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy . ( Funded by Medivation and Astellas Pharma Global Development ; AFFIRM Clinical Trials.gov number , NCT00974311 . ) While programmed cell death 1 ( PD-1 ) inhibitors have shown clear anti-tumor efficacy in several solid tumors , prior results in men with metastatic castration resistant prostate cancer ( mCRPC ) showed no evidence of activity . Here we report unexpected antitumor activity seen in mCRPC patients treated with the anti-PD-1 antibody pembrolizumab . Patients with evidence of progression on enzalutamide were treated with pembrolizumab 200 mg IV every 3 weeks for 4 doses ; pembrolizumab was added to st and ard dose enzalutamide . Three of the first ten patients enrolled in this ongoing phase II trial experienced rapid prostate specific antigen ( PSA ) reductions to ≤ 0.2 ng/ml . Two of these three patients had measurable disease upon study entry ; both achieved a partial response . There were three patients with significant immune-related adverse events . One had grade 2 myositis , one had grade 3 hypothyroidism , and one had grade 2 hypothyroidism . None of these patients had a response . Two of the three responders had a baseline tumor biopsy . Immunohistochemistry from those biopsies showed the presence of CD3 + , CD8 + , and CD163 + leukocyte infiltrates and PD-L1 expression . Genetic analysis of the two responders revealed markers of microsatellite instability in one . The surprising and robust responses seen in this study should lead to re-examination of PD-1 inhibition in prostate cancer R and omised controlled trials and population -based observational research : partners in the evolution of medical OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Purpose : To evaluate the efficacy , safety , biomarkers , and pharmacokinetics of rilotumumab , a fully human , monoclonal antibody against hepatocyte growth factor (HGF)/scatter factor , combined with mitoxantrone and prednisone ( MP ) in patients with castration-resistant prostate cancer ( CRPC ) . Experimental Design : This double-blinded phase II study r and omized ( 1:1:1 ) patients with progressive , taxane-refractory CRPC to receive MP ( 12 mg/m2 i.v . day 1 , 5 mg twice a day orally days 1–21 , respectively ) plus 15 mg/kg rilotumumab , 7.5 mg/kg rilotumumab , or placebo ( i.v . day 1 ) every 3 weeks . The primary endpoint was overall survival ( OS ) . Results : One hundred and forty-four patients were r and omized . Median OS was 12.2 versus 11.1 months [ HR , 1.10 ; 80 % confidence interval ( CI ) , 0.82–1.48 ] in the combined rilotumumab versus control arms . Median progression-free survival was 3.0 versus 2.9 months ( HR , 1.02 ; 80 % CI , 0.79–1.31 ) . Treatment appeared well tolerated with peripheral edema ( 24 % vs. 8 % ) being more common with rilotumumab . A trend toward unfavorable OS was observed in patients with high tumor MET expression regardless of treatment . Soluble MET levels increased in all treatment arms . Total HGF levels increased in the rilotumumab arms . Rilotumumab showed linear pharmacokinetics when co-administered with MP . Conclusions : Rilotumumab plus MP had manageable toxicities and showed no efficacy improvements in this estimation study . High tumor MET expression may identify patients with CRPC with poorer prognosis . Clin Cancer Res ; 19(1 ) ; 215–24 . © 2012 AACR BACKGROUND Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced , hormone-refractory prostate cancer , but it does not improve survival . We compared such treatment with docetaxel plus prednisone in men with this disease . METHODS From March 2000 through June 2002 , 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were r and omly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks , 75 mg of docetaxel per square meter every three weeks , or 30 mg of docetaxel per square meter weekly for five of every six weeks . The primary end point was overall survival . Secondary end points were pain , prostate-specific antigen ( PSA ) levels , and the quality of life . All statistical comparisons were against mitoxantrone . RESULTS As compared with the men in the mitoxantrone group , men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 ( 95 percent confidence interval , 0.62 to 0.94 ; P=0.009 by the stratified log-rank test ) and those given weekly docetaxel had a hazard ratio for death of 0.91 ( 95 percent confidence interval , 0.75 to 1.11 ; P=0.36 ) . The median survival was 16.5 months in the mitoxantrone group , 18.9 months in the group given docetaxel every 3 weeks , and 17.4 months in the group given weekly docetaxel . Among these three groups , 32 percent , 45 percent , and 48 percent of men , respectively , had at least a 50 percent decrease in the serum PSA level ( P<0.001 for both comparisons with mitoxantrone ) ; 22 percent , 35 percent ( P=0.01 ) , and 31 percent ( P=0.08 ) had predefined reductions in pain ; and 13 percent , 22 percent ( P=0.009 ) , and 23 percent ( P=0.005 ) had improvements in the quality of life . Adverse events were also more common in the groups that received docetaxel . CONCLUSIONS When given with prednisone , treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain , serum PSA level , and quality of life , as compared with mitoxantrone plus prednisone BACKGROUND In the AFFIRM trial of patients with metastatic castration-resistant prostate cancer after progression with docetaxel treatment , enzalutamide significantly increased overall survival compared with placebo . Here we present the prospect ively defined analyses of some secondary endpoints , including occurrence of skeletal-related events , measures of pain control , and patient-reported health-related quality of life ( HRQoL ) . METHODS In this phase 3 , double-blind trial , patients were r and omly assigned ( 2:1 ) to receive enzalutamide 160 mg/day or placebo orally , stratified by ECOG baseline performance status ( 0 or 1 vs 2 ) and mean pain score ( Brief Pain Inventory-Short Form [ BPI-SF ] question 3 worst pain , score ≤3 vs ≥4 ) . Secondary endpoints were time to first skeletal-related event ( defined as radiation therapy or surgery to bone ) ; change from baseline to week 13 in pain severity and interference ; pain palliation and progression at week 13 ; time to pain progression ; overall improvement in HRQoL ; improvements in HRQoL domains ; and time to HRQoL deterioration . Analysis was done on the intention-to-treat population for each endpoint . AFFIRM is registered with Clinical Trials.gov , number NCT00974311 . FINDINGS Median time to first skeletal-related event in the enzalutamide ( n=800 ) and placebo ( n=399 ) groups was 16·7 months ( 95 % CI 14·6 to 19·1 ) and 13·3 months ( 95 % CI 9·9 to not yet reached ) , respectively ( hazard ratio [ HR ] 0·69 [ 95 % CI 0·57 - 0·84 ] ; p=0·0001 ) . Pain progression at week 13 occurred in 174 ( 28 % ) of 625 evaluable patients in the enzalutamide group versus 101 ( 39 % ) of 259 patients in the placebo group ( difference -11·2 % , 95 % CI -18·1 to -4·3 ; p=0·0018 ) . Median time to pain progression was not yet reached in the enzalutamide group ( 95 % CI not yet reached to not yet reached ) versus 13·8 ( 13·8 to not yet reached ) months in the placebo group ( HR 0·56 [ 95 % CI 0·41 to 0·78 ] ; p=0·0004 ) . Mean treatment effects for pain severity ( mean change from baseline in the enzalutamide group -0·15 , 95 % CI -0·28 to -0·02 , vs placebo 0·50 , 0·29 to 0·70 ; difference -0·65 , 95 % CI -0·89 to -0·41 ; p<0·0001 ) and interference ( -0·01 , -0·18 to 0·16 , vs 0·74 , 0·47 to 1·00 ; respectively , difference -0·74 , 95 % -1·06 to -0·43 ; p<0·0001 ) were significantly better with enzalutamide than with placebo . 22 ( 45 % ) of 49 evaluable patients in the enzalutamide group reported pain palliation at week 13 versus one ( 7 % ) of 15 in the placebo group ( difference 38·2 % , 95 % CI 19·4 - 57·0 ; p=0·0079 ) . Overall improvement in HRQoL was reported in more patients receiving enzalutamide ( 275 [ 42 % ] of 652 ) than in those receiving placebo ( 36 [ 15 % ] of 248 ; p<0·0001 ) . Patients in the enzalutamide group had longer median time to HRQoL deterioration than did those in the placebo group ( 9·0 months , 95 % CI 8·3 - 11·1 , vs 3·7 months , 95 % CI 3·0 - 4·2 ; HR 0·45 , 95 % CI 0·37 - 0·55 ; p<0·0001 ) in risk of deterioration . INTERPRETATION Our results show that , in addition to improving overall survival , enzalutamide improves wellbeing and everyday functioning of patients with metastatic castration-resistant prostate cancer . FUNDING Astellas Pharma and Medivation To determine the impact of prophylaxis with granulocyte-colony stimulating growth factor ( G-CSF ) on the risk of febrile neutropenia in a cohort of patients enrolled at the University Federico II of Naples and treated with cabazitaxel for metastatic castration-resistant prostate cancer ( mCRPC ) . We carried out a retrospective review of prospect ively collected data of patients enrolled at our institution in a compassionate-use programme with cabazitaxel , aim ed at providing early access to the drug before its commercial availability in mCRPC patients . Besides baseline clinical and demographic characteristics , data on treatment efficacy and toxicity , as well as those on the use of G-CSF per patient per cycle were extracted . Progression-free survival and overall survival were calculated using the Kaplan – Meier method . Fisher ’s exact test was used to explore a relationship between a single event of grade 3 or more neutropenia or febrile neutropenia and previous use of G-CSF . Univariate analysis was carried out to evaluate predictors of grade 3 or more neutropenia and /or febrile neutropenia . Of 34 patients enrolled at our institution from December 2010 to December 2011 , 32 had received at least one dose of cabazitaxel and were included in the analysis . Patients received a median of 10 cabazitaxel cycles . Grade 3 or more neutropenia was common , occurring in 64.5 % of patients . Three patients ( 9.3 % ) developed febrile neutropenia . Twenty-seven patients received prophylaxis with G-CSF during at least one cycle using peg-filgrastim . The risk of grade 3 or more neutropenia and /or febrile neutropenia per patient and per cycle was seven times lower when G-CSF was used . Baseline neutrophil count of less than 4570/mm3 was the strongest predictor of grade 3 or more neutropenia and /or febrile neutropenia . No toxic death was reported . Only one patient discontinued cabazitaxel because of an adverse event . Our analysis suggests that prophylaxis with peg-filgrastim may considerably reduce the incidence of grade 3 or more neutropenia and , possibly , of febrile neutropenia in mCRPC patients treated with cabazitaxel . Further analyses involving a larger population are warranted to confirm our results |
1,638 | 29,662,064 | There is some evidence that electronic alerts reduce excessive prescribing of SABAs , when delivered as part of a multicomponent intervention in an integrated health care system . | Computers are increasingly used to improve prescribing decisions in the management of long-term conditions however the effects on asthma prescribing remain unclear .
We aim ed to synthesis e the evidence for the use of computerised alerts that identify excessive prescribing of short-acting beta2-agonists ( SABAs ) to improve asthma management for people with asthma . | Abstract Objective : To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care . Design : A before and after pragmatic cluster r and omised controlled trial utilising a two by two incomplete block design . Setting : 60 general practice s in north east Engl and . Participants : General practitioners and practice nurses in the study practice s and their patients aged 18 or over with angina or asthma . Main outcome measures : Adherence to the guidelines , based on review of case notes and patient reported generic and condition specific outcome measures . Results : The computerised decision support system had no significant effect on consultation rates , process of care measures ( including prescribing ) , or any patient reported outcomes for either condition . Levels of use of the software were low . Conclusions : No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care . This was probably due to low levels of use of the software , despite the system being optimised as far as was technically possible . Even if the technical problems of producing a system that fully supports the management of chronic disease were solved , there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex , multiple conditions Objective To develop an empirically based framework of the aspects of r and omised controlled trials addressed by qualitative research . Design Systematic mapping review of qualitative research undertaken with r and omised controlled trials and published in peer- review ed journals . Data sources MEDLINE , Pre MEDLINE , EMBASE , the Cochrane Library , Health Technology Assessment , PsycINFO , CINAHL , British Nursing Index , Social Sciences Citation Index and ASSIA . Eligibility criteria Articles reporting qualitative research undertaken with trials published between 2008 and September 2010 ; health research , reported in English . Results 296 articles met the inclusion criteria . Articles focused on 22 aspects of the trial within five broad categories . Some articles focused on more than one aspect of the trial , totalling 356 examples . The qualitative research focused on the intervention being trialled ( 71 % , 254/356 ) ; the design , process and conduct of the trial ( 15 % , 54/356 ) ; the outcomes of the trial ( 1 % , 5/356 ) ; the measures used in the trial ( 3 % , 10/356 ) ; and the target condition for the trial ( 9 % , 33/356 ) . A minority of the qualitative research was undertaken at the pretrial stage ( 28 % , 82/296 ) . The value of the qualitative research to the trial itself was not always made explicit within the articles . The potential value included optimising the intervention and trial conduct , facilitating interpretation of the trial findings , helping trialists to be sensitive to the human beings involved in trials , and saving money by steering research ers towards interventions more likely to be effective in future trials . Conclusions A large amount of qualitative research undertaken with specific trials has been published , addressing a wide range of aspects of trials , with the potential to improve the endeavour of generating evidence of effectiveness of health interventions . Research ers can increase the impact of this work on trials by undertaking more of it at the pretrial stage and being explicit within their articles about the learning for trials and evidence -based practice Background Computer-based decision support has been effective in providing alerts for preventive care . Our objective was to determine whether a personalized asthma management computer-based decision support increases the quality of asthma management and reduces the rate of out-of-control episodes . Methods A cluster-r and omized trial was conducted in Quebec , Canada among 81 primary care physicians and 4447 of their asthmatic patients . Patients were followed from the first visit for 3–33 months . The physician control group used the Medical Office of the 21st century ( MOXXI ) system , an integrated electronic health record . A custom-developed asthma decision support system was integrated within MOXXI and was activated for physicians in the intervention group . Results At the first visit , 9.8 % ( intervention ) to 12.9 % ( control ) of patients had out-of-control asthma , which was defined as a patient having had an emergency room visit or hospitalization for respiratory-related problems and /or more than 250 doses of fast-acting β-agonist ( FABA ) dispensed in the past 3 months . By the end of the trial , there was a significant increase in the ratio of doses of inhaled corticosteroid use to fast-acting β-agonist ( 0.93 vs. 0.69 : difference : 0.27 ; 95 % CI : 0.02–0.51 ; P = 0.03 ) in the intervention group . The overall out-of-control asthma rate was 54.7 ( control ) and 46.2 ( intervention ) per 100 patients per year ( 100 PY ) , a non-significant rate difference of −8.7 ( 95 % CI : −24.7 , 7.3 ; P = 0.29 ) . The intervention ’s effect was greater for patients with out-of-control asthma at the beginning of the study , a group who accounted for 44.7 % of the 5597 out-of-control asthma events during follow-up , as there was a reduction in the event rate of −28.4 per 100 PY ( 95 % CI : −55.6 , −1.2 ; P = 0.04 ) compared to patients with in-control asthma at the beginning of the study ( −0.08 [ 95 % CI : −10.3 , 8.6 ; P = 0.86 ] ) . Discussion This study evaluated the effectiveness of a novel computer-assisted ADS system that facilitates systematic monitoring of asthma control status , follow-up of patients with out of control asthma , and evidence -based , patient-specific treatment recommendations . We found that physicians were more likely to use ADS for out-of-control patients , that in the majority of these patients , they were advised to add an inhaled corticosteroid or a leukotriene inhibitor to the patient s treatment regimen , and the intervention significantly increased the mean ratio of inhaled corticosteroids to FABA during follow-up . It also reduced the rate of out-of-control episodes during follow up among patients whose asthma was out-of-control at the time of study entry . Future research should assess whether coupling patient-specific treatment recommendations , automated follow-up , and home care with comparative feedback on quality and outcomes of care can improve guideline adoption and care outcomes . Conclusions A primary care-personalized asthma management system reduced the rate of out-of-control asthma episodes among patients whose asthma was poorly controlled at the study ’s onset . Trial Registration Clinical trials.gov Identifier : NCT00170248 http:// clinical OBJECTIVE Computer-based clinical decision support systems ( CDSSs ) vary greatly in design and function . Using a taxonomy that we had previously developed , we describe the characteristics of CDSSs reported in the literature . METHODS We search ed PubMed and the Cochrane Library for r and omized controlled trials ( RCTs ) published in English between 1998 and 2003 that evaluated CDSSs . We coded each CDSS using our taxonomy . RESULTS 58 studies met our inclusion criteria . The 74 reported CDSSs varied greatly in context of use , knowledge and data sources , nature of decision support offered , information delivery , and workflow impact . Two distinct subsets of CDSSs were seen : patient-directed systems that provided decision support for preventive care or health-related behaviors via mail or phone ( 38 % of systems ) , and inpatient systems targeting clinicians with online decision support and direct online execution of the recommendations ( 18 % ) . 84 % of the CDSSs required extra staffing for h and ling CDSS-related input or output . CONCLUSION Reported CDSSs are heterogeneous along many dimensions . Caution should be taken in generalizing the results of CDSS RCTs to different clinical or workflow setting Beta‐agonist overuse is associated with adverse outcomes in asthma , however , the relationships between different metrics of salbutamol use and future risk are uncertain . BACKGROUND US national guidelines recommend assessing short-acting beta-agonist ( SABA ) medication use as a marker of asthma severity and control . However , the relationship between recent SABA use and asthma exacerbations is not currently known . OBJECTIVE To evaluate the proximal relationship between the type and frequency of SABA use and asthma-related outcomes . METHODS We evaluated SABA use among patients with asthma ages 5 to 56 years who were members of a large health maintenance organization in southeast Michigan . Frequency of use was estimated from pharmacy data assessing the timing and amount of SABA fills . Cox proportional hazards models were used to examine the prospect i ve relationship between average daily SABA use for 3 months and outcomes associated with poor asthma control ( ie , oral corticosteroids use , asthma-related emergency department visits , and asthma-related hospitalizations ) . We separately accounted for SABA metered-dose inhaler ( MDI ) and SABA nebulizer use . RESULTS Of the 2,056 patients who met study criteria , 1,569 ( 76.3 % ) had used a SABA medication in their baseline year . After adjusting for potential confounders , SABA nebulizer use was associated with asthma-related emergency department visits ( adjusted hazard ratio [ aHR ] , 6.32 ; 95 % confidence interval [ CI ] , 2.38 to 16.80 ) and asthma-related hospitalizations ( aHR , 21.62 ; 95 % CI , 3.17 to 147.57 ) . In contrast , frequency of SABA MDI use was not associated with these outcomes . CONCLUSIONS Frequency of SABA use during a 3-month period was associated with poor asthma outcomes . The relationship with poor asthma outcomes was strongest for SABA nebulizer use , suggesting that the type of SABA used is also of prognostic importance PRIMARY OBJECTIVE To investigate whether computer decision support software used in the management of patients with asthma improves clinical outcomes . RESEARCH DESIGN R and omized controlled trial with practice s each reporting on 30 patients with asthma over a 6 month period . METHODS AND PROCEDURES 447 patients were r and omly selected from practice asthma registers managed by 17 general practice s from throughout the UK . Intervention practice s used the software during consultations with these patients throughout the study while control practice s did not . MAIN OUTCOMES AND RESULTS Practice consultations , acute exacerbations of asthma , hospital contacts , symptoms on assessment and medication use . A smaller proportion of patients within the intervention group initiated practice consultations for their asthma : 34 ( 22 % ) vs 111 ( 34 % ) , odds ratio ( OR ) = 0.59 , 95 % confidence interval ( CI ) ( 0.37 - 0.95 ) ; and suffered acute asthma exacerbations : 12 ( 8 % ) vs 57 ( 17 % ) , OR = 0.43 , 95 % CI = 0.21 - 0.85 six months after the introduction of the computer decision support software . There were no discernable differences in reported symptoms , maintenance prescribing or use of hospital services between the two groups . CONCLUSION The use of computer decision support software that implements guidelines during patient consultations may improve clinical outcomes for patients with asthma BACKGROUND Excessive use of short-acting β2-agonists ( SABA ) indicates impaired asthma control . OBJECTIVE To determine whether real-time outreach to excessive SABA users reduces SABA canister dispensings . METHODS After real-time determination of a seventh SABA canister dispensing in the prior 12 months by using informational pharmacy technology , 12 to 56 year old patients with physician-coded asthma and inhaled corticosteroid dispensing were block r and omized by prior asthma specialist care and medication step-care level into intervention ( n = 1001 ) and control groups ( n = 998 ) . Intervention included real-time letter notification to patients and an electronic message to their physician with management suggestions , including facilitated allergy referral for patients without prior asthma specialist care . The control group received this organization 's st and ard asthma care management without research contact . Frequency of the seventh SABA canister dispensing in the follow-up year was the primary outcome . RESULTS Compared with controls , intervention patients reached 7 SABA canister dispensings less frequently ( 50.7 % vs 57.1 % ; risk ratio 0.89 [ 95 % CI , 0.82 - 0.97 ] ; P = .007 ) and later ( hazard ratio 0.80 [ 95 % CI , 0.71 - 0.91 ; P < .001 ) . SABA canister dispensings ( mean ± SD ) were less in intervention ( 7.5 ± 4.9 canisters ) than controls ( 8.6 ± 5.3 canisters ) ( rate ratio 0.87 [ 95 % CI , 0.82 - 0.93 ] ; P < .001 ) . The intervention reduced the risk of ≥7 SABA canister dispensings in patients without specialist care compared with patients with specialist care in the prior 3 years ( P < .001 ) ( P = .04 for interaction by prior specialist care ) . Visits to allergists were more frequent for intervention patients ( 30.9 % ) than for control patients ( 16.8 % ) ( risk ratio 1.83 [ 95 % CI , 1.54 - 2.16 ] ; P < .001 ) . Asthma exacerbations were unaffected . CONCLUSIONS A novel administrative-based asthma outreach program improves markers of asthma impairment in patients without prior asthma specialist care and is adaptable to managed care organizations with electronic medical records |
1,639 | 29,108,442 | Conclusion : Acute and chronic exercise appears to play a pronounced effect on memory function among young to middle-aged adults . | Objective : To systematic ally summarize the experimental effects of exercise on cognitive-related memory function among young to middle-aged adults , which has yet to be done in the literature . | In the current work we asked whether executive function , as measured by tests of working memory capacity , might benefit from an acute bout of exercise and , more specifically , whether individuals who are lower or higher in working memory to begin with would be more or less affected by an exercise manipulation . Healthy adults completed working memory measures in a nonexercise ( baseline ) session and immediately following a 30-min self-paced bout of exercise on a treadmill ( exercise session ) . Sessions were conducted 1 week apart and session order was counterbalanced across participants . A significant Session x Working Memory interaction was obtained such that only those individuals lowest in working memory benefited from the exercise manipulation . This work suggests that acute bouts of exercise may be most beneficial for healthy adults whose cognitive performance is generally the lowest , and it demonstrates that the impact of exercise on cognition is not uniform across all individuals The effects of acute aerobic exercise on cognitive functions in humans have been the subject of much investigation ; however , these studies are limited by several factors , including a lack of r and omized controlled design s , focus on only a single cognitive function , and testing during or shortly after exercise . Using a r and omized controlled design , the present study asked how a single bout of aerobic exercise affects a range of frontal- and medial temporal lobe-dependent cognitive functions and how long these effects last . We r and omly assigned 85 subjects to either a vigorous intensity acute aerobic exercise group or a video watching control group . All subjects completed a battery of cognitive tasks both before and 30 , 60 , 90 , or 120 min after the intervention . This battery included the Hopkins Verbal Learning Test-Revised , the Modified Benton Visual Retention Test , the Stroop Color and Word Test , the Symbol Digit Modalities Test , the Digit Span Test , the Trail Making Test , and the Controlled Oral Word Association Test . Based on these measures , composite scores were formed to independently assess prefrontal cortex- and hippocampal-dependent cognition . A three-way mixed Analysis of Variance was used to determine whether differences existed between groups in the change in cognitive function from pre- to post-intervention testing . Acute exercise improved prefrontal cortex- but not hippocampal-dependent functioning , with no differences found between delay groups . Vigorous acute aerobic exercise has beneficial effects on prefrontal cortex-dependent cognition and these effects can last for up to 2 hr after exercise Cognitive dysfunction has been repeatedly observed in major depressive disorder ( MDD ) , particularly in areas of attention , verbal and nonverbal learning and memory , and executive functioning . Exercise has been shown to improve cognitive outcomes in other population s , including age-associated cognitive decline , but has not to our knowledge been investigated as an augmentation strategy in depression . This study evaluated the effectiveness of exercise augmentation on cognitive performance in persons with MDD and residual symptoms that included cognitive complaints following initial treatment with a selective serotonin reuptake inhibitor ( SSRI ) . Participants enrolled in the Treatment with Exercise Augmentation for Depression ( TREAD ) study were r and omized to receive either a low or high dose exercise regimen . TREAD participants who provided informed consent for the current study completed Cambridge Neuropsychological Test Automated Battery measures assessing Attention , Visual Memory , Executive Function/Set-shifting and Working Memory , and Executive Function/Spatial Planning domains . Data were analyzed for 39 participants completing both baseline and Week 12 cognitive testing . Overall tests indicated a significant task × group × time interaction for the Executive Function/Set-shifting and Working Memory domain . Post-hoc tests indicated improvements in high dose exercisers ' spatial working memory , but decreases in spatial working memory and set-shifting outcomes in low dose exercisers . Both groups improved on measures of psychomotor speed , attention , visual memory and spatial planning . This study suggests a dose-response effect of exercise in specific executive function and working memory tasks among depressed persons with a partial response to SSRI and cognitive complaints , with some cognitive functions improving regardless of exercise dose Persistent long-term memory depends on successful stabilization and integration of new memories after initial encoding [ 1 , 2 ] . This consolidation process is thought to require neuromodulatory factors such as dopamine , noradrenaline , and brain-derived neurotrophic factor [ 3 - 7 ] . Without the release of such factors around the time of encoding , memories will decay rapidly [ 3 , 5 , 6 , 8 ] . Recent studies have shown that physical exercise acutely stimulates the release of several consolidation-promoting factors in humans [ 9 - 14 ] , raising the question of whether physical exercise can be used to improve memory retention [ 15 - 17 ] . Here , we used a single session of physical exercise after learning to exogenously boost memory consolidation and thus long-term memory . Three groups of r and omly assigned participants first encoded a set of picture-location associations . Afterward , one group performed exercise immediately , one 4 hr later , and the third did not perform any exercise . Participants otherwise underwent exactly the same procedures to control for potential experimental confounds . Forty-eight hours later , participants returned for a cued-recall test in a magnetic resonance scanner . With this design , we could investigate the impact of acute exercise on memory consolidation and retrieval-related neural processing . We found that performing exercise 4 hr , but not immediately , after encoding improved the retention of picture-location associations compared to the no-exercise control group . Moreover , performing exercise after a delay was associated with increased hippocampal pattern similarity for correct responses during delayed retrieval . Our results suggest that appropriately timed physical exercise can improve long-term memory and highlight the potential of exercise as an intervention in educational and clinical setting OBJECTIVE Physical exercise has been linked to higher cognitive functioning and enhanced brain plasticity in aging humans . The most consistent positive effects have been reported for executive functions associated with frontal brain regions . In rodents , however , running has been shown to induce functional and structural changes in the hippocampus , a brain region known to be important for memory . It is still a matter of debate which cognitive functions are susceptible to exercise and whether an increase in cardiovascular fitness is beneficial for cognitive functioning . Moreover , little is known about the impact of exercise on cognition in middle-aged humans . METHOD Sixty-eight sedentary men and women between 40 and 56 years of age were r and omly assigned to one of two training programs : aerobic endurance training ( cycling ) or nonendurance training ( stretching/coordination ) . Both groups exercised twice a week for six months . Additionally , a sedentary control group was tested . At baseline and after six months , episodic memory , perceptual speed , executive functions , and spatial reasoning were assessed with st and ardized psychometric tests , and all participants underwent a cardiovascular fitness test . RESULTS Significant improvements in memory were observed in both the cycling and the stretching/coordination group as compared with the sedentary control group . The improvement in episodic memory correlated positively with the increase in cardiovascular fitness . The stretching/coordination training particularly improved selective attention as compared with the cycling training . CONCLUSIONS The results suggest that cardiovascular fitness has beneficial effects even in high-functioning middle-aged participants , but that these benefits are very specific to memory functions rather than a wider range of cognitive functions Cognitive training has received a lot of attention recently , yielding findings that can be conflicting and controversial . In this paper , we present a novel approach to cognitive training based on complex motor activities . In a r and omized controlled design , participants were assigned to one of three conditions : aerobic exercise , working memory training or design ed sport -- an intervention specifically tailored to include both physical and cognitive dem and s. After training for eight weeks , the design ed sport group showed the largest gains in all cognitive measures , illustrating the efficacy of complex motor activities to enhance cognition . Design ed sport training also revealed impressive health benefits , namely decreased heart rate and blood pressure . In this period of skepticism over the efficacy of computerized cognitive training , we discuss the potential of ecological interventions targeting both cognition and physical fitness , and propose some possible applications This condensed review gives an overview about two method ological approaches to study the impact of physical activity on cognition in elderly , namely cross-sectional studies and r and omized controlled intervention studies with pre- and post- measures . Moreover , this review includes studies investigating different types of physical activity and their relation to cognitive functions in older age . Behavioral data are considered but the main focus lies on neuroscientific methods like event-related potentials ( ERPs ) and functional magnetic resonance imaging ( fMRI ) This is the first r and omized , controlled study comparing the cognitive effects of transcranial laser stimulation and acute aerobic exercise on the same cognitive tasks . We examined whether transcranial infrared laser stimulation of the prefrontal cortex , acute high-intensity aerobic exercise , or the combination may enhance performance in sustained attention and working memory tasks . Sixty healthy young adults were r and omly assigned to one of the following four treatments : ( 1 ) low-level laser therapy ( LLLT ) with infrared laser to two forehead sites while seated ( total 8 min , 1064 nm continuous wave , 250 mW/cm2 , 60 J/cm2 per site of 13.6 cm2 ) ; ( 2 ) acute exercise ( EX ) of high-intensity ( total 20 min , with 10-min treadmill running at 85–90 % VO2max ) ; ( 3 ) combined treatment ( LLLT + EX ) ; or ( 4 ) sham control ( CON ) . Participants were tested for prefrontal measures of sustained attention with the psychomotor vigilance task ( PVT ) and working memory with the delayed match-to- sample task ( DMS ) before and after the treatments . As compared to CON , both LLLT and EX reduced reaction time in the PVT [ F(1.56 ) = 4.134 , p = 0.01 , η2 = 0.181 ] and increased the number of correct responses in the DMS [ F(1.56 ) = 4.690 , p = 0.005 , η2 = 0.201 ] , demonstrating a significant enhancing effect of LLLT and EX on cognitive performance . LLLT + EX effects were similar but showed no significantly greater improvement on PVT and DMS than LLLT or EX alone . The transcranial infrared laser stimulation and acute aerobic exercise treatments were similarly effective for cognitive enhancement , suggesting that they augment prefrontal cognitive functions similarly OBJECTIVE To simultaneously examine the effects of acute exercise intensity and free-living physical activity and sedentary behavior on cognitive function in young , healthy adults . PATIENTS AND METHODS Using a counterbalanced , crossover , r and omized controlled design , 87 young adults ( mean age , 21.4 years ) completed various cognitive assessment s with and without an acute bout of exercise preceding the assessment . Participants were r and omized into 1 of 4 groups to complete a 30-minute bout of acute exercise : control ( no exercise ) , light intensity ( 40%-50 % of predicted maximum heart rate [ HR(max ) ] ) , moderate intensity ( 51%-70 % of predicted HR(max ) ) , or vigorous intensity ( 71%-85 % of predicted HR(max ) ) . Subjectively and objective ly determined ( accelerometry ) physical activity and sedentary behavior were assessed to examine the association between these free-living behaviors and cognitive function . The study duration was August 26 , 2013 , to September 11 , 2014 . RESULTS Concentration-related cognition ( mean ± SD Feature Match test score ) was significantly higher after a 30-minute acute bout of moderate-intensity exercise ( 145.1±26.9 ) compared with cognitive assessment without exercise ( 121.3±19.2 ; P=.004 ) . Furthermore , question naire-determined sedentary behavior was inversely associated with visual attention and task switching ( Trail Making Test A score ) ( β=-0.23 ; P=.04 ) . Last , estimated cardiorespiratory fitness ( volume of maximum oxygen consumption ) was positively associated with reasoning-related cognitive function ( Odd One Out test score ) ( β=0.49 ; P=.05 ) ; when adding metabolic equivalent of task minutes per week to this model , the results were not significant ( β=0.47 ; P=.07 ) . CONCLUSION These findings provide some support for acute moderate-intensity exercise , sedentary behavior , and cardiorespiratory fitness being associated with executive functioning-related cognitive function in young , healthy adults In this study , we tested the effect of acute exercise on long-term memory , specifically the timing of exercise relative to the memory challenge . We assessed memory via paragraph recall , in which participants listened to two paragraphs ( exposure ) and recounted them following a 35-min delay . Participants ( n = 48 ) were r and omly assigned to one of three groups : exercise prior to exposure , exercise after exposure , or no-exercise . Exercise consisted of 30 min on a cycle ergometer , including 20 min at moderate intensity . Only the exercise-prior group recalled significantly more than the control group ( p < .05 ) . Differences among the exercise groups failed to reach significance ( p = .09 ) . Results indicated that acute exercise positively influenced recall and that exercise timing relative to memory task may have an impact on this effect There is a paucity of methods for improving the affective experience of exercise . We tested a novel method based on discoveries about the relation between exercise intensity and pleasure , and lessons from behavioral economics . We examined the effect of reversing the slope of pleasure during exercise from negative to positive on pleasure and enjoyment , remembered pleasure , and forecasted pleasure . Forty-six adults were r and omly assigned to a 15-min bout of recumbent cycling of either increasing intensity ( 0 - 120 % of watts corresponding to the ventilatory threshold ) or decreasing intensity ( 120 - 0 % ) . Ramping intensity down , thereby eliciting a positive slope of pleasure during exercise , improved postexercise pleasure and enjoyment , remembered pleasure , and forecasted pleasure . The slope of pleasure accounted for 35 - 46 % of the variance in remembered and forecasted pleasure from 15 min to 7 days postexercise . Ramping intensity down makes it possible to combine exposure to vigorous and moderate intensities with a pleasant affective experience Objective : In the present study , we examined the effect of working while seated , while st and ing , or while walking on measures of short-term memory , working memory , selective and sustained attention , and information-processing speed . Background : The advent of computer-based technology has revolutionized the adult workplace , such that average adult full-time employees spend the majority of their working day seated . Prolonged sitting is associated with increasing obesity and chronic health conditions in children and adults . One possible intervention to reduce the negative health impacts of the modern office environment involves modifying the workplace to increase incidental activity and exercise during the workday . Although modifications , such as sit-st and desks , have been shown to improve physiological function , there is mixed information regarding the impact of such office modification on individual cognitive performance and thereby the efficiency of the work environment . Method : In a fully counterbalanced r and omized control trial , we assessed the cognitive performance of 45 undergraduate students for up to a 1-hr period in each condition . Results : The results indicate that there is no significant change in the measures used to assess cognitive performance associated with working while seated , while st and ing , or while walking at low intensity . Conclusion : These results indicate that cognitive performance is not de grade d with short-term use of alternate workstations In a free recall experiment , participants learned lists of words in two physiological states : at rest and while exercising aerobically on a bicycle ergometer . Recall of the words was required in either the state consistent with learning or in the alternative state . Word lists learned during aerobic exercise were recalled best during aerobic exercise and vice versa . Greater changes in heart rate in the changed state conditions were associated with greater retrieval decrements . Recall levels for words both learned and recalled at exercise were equivalent to those for words both learned and recalled at rest . This finding rules out the possibility that exercise per se interfered with the original learning . The study is consistent with the view that state-dependent memory should be viewed as a particular form of cue-dependent memory Two questions about the relationship between arousal and memory were investigated : First , does the source of arousal influence memory , and , second , what impact does arousal have on memory for detail ? In Experiment 1 , physiological arousal ( running or not running in place ) was factorially combined with emotional arousal ( viewing a neutral or an emotional slide sequence ) . Recognition memory was tested for gist , central detail , and background detail . Experiments 2 and 3 were similar to Experiment 1 , with the exception that a cued recall task was used in Experiment 2 and physiological arousal was manipulated with stationary biking in Experiment 3 . The results of these experiments indicated that physiological arousal had little impact on memory and that emotional arousal led to improvements in memory for both central and background detail . Overall , these results supported the notions that the source of arousal is an important determinant of an event ’s memorability ( Christianson , 1992a ) and that emotional arousal serves to enhance the scope of memory ( i.e. , flashbulb memory ; Brown & Kulik , 1977 ) Substantial evidence from animal studies suggests that enhanced memory associated with emotional arousal results from an activation of beta-adrenergic stress hormone systems during and after an emotional experience . To examine this implication in human subjects , we investigated the effect of the beta-adrenergic receptor antagonist propranolol hydrochloride on long-term memory for an emotionally arousing short story , or a closely matched but more emotionally neutral story . We report here that propranolol significantly impaired memory of the emotionally arousing story but did not affect memory of the emotionally neutral story . The impairing effect of propranolol on memory of the emotional story was not due either to reduced emotional responsiveness or to nonspecific sedative or attentional effects . The results support the hypothesis that enhanced memory associated with emotional experiences involves activation of the beta-adrenergic system |
1,640 | 23,320,860 | The local application of chlorhexidine and metronidazole showed a minimal effect when compared with placebo ( WMD between 0.1 and 0.4 mm ) .
The scientific evidence supports the adjunctive use of local antimicrobials to debridement in deep or recurrent periodontal sites , mostly when using vehicles with proven sustained release of the antimicrobial | AIMS To up date the existing scientific evidence on the efficacy of local antimicrobials as adjuncts to subgingival debridement in the treatment of chronic periodontitis . | BACKGROUND The aim of this clinical study was to evaluate the association of locally delivered doxycycline ( 10 % ) with scaling and root planing in the periodontal treatment of smokers . METHODS Forty-three patients with chronic periodontitis and a minimum of four pockets ( > or = 5 mm ) on anterior teeth that bled on probing were selected . Patients were r and omly assigned to scaling and root planing ( SRP ) or scaling and root planing followed by local application of doxycycline ( SRP-D ) . Plaque , bleeding on probing , gingival recession , relative attachment level ( RAL ) , and probing depth ( PD ) were recorded at baseline , 45 days , and 3 and 6 months . Differences between baseline and each period were considered for analysis . RESULTS At 6 months , no difference was found between groups regarding plaque , bleeding reduction , gingival recession or PD ( P > 0.05 ) . However , RAL gain was greater for SRP-D ( 1.63 + /- 0.93 mm ) than for SRP ( 1.04 + /- 0.71 mm ) ( P = 0.025 ) . In addition , deep pockets ( > or = 7 mm ) showed a significant reduction ( 3.78 + /- 1.41 versus 2.60 + /- 1.28 mm , P = 0.039 ) and RAL gain ( 2.54 + /- 1.27 mm versus 1.29 + /- 0.95 mm , P = 0.01 ) when doxycycline was applied . The proportion of sites showing RAL gain of 1 to 2 mm was 36.8 % versus 21.7 % for SRP-D and SRP , respectively ( P = 0.01 ) . CONCLUSION The use of locally delivered doxycycline may constitute an important adjunct for the treatment of severe periodontal disease in smokers BACKGROUND Although scaling and root planing are considered the therapeutic st and ard for periodontitis , weakly responding sites often occur . To improve treatment outcome , several chemomechanical treatment concepts have been developed . Recently , the clinical surplus value of a highly concentrated chlorhexidine varnish has been shown when used as an adjunct to sequential scaling and root planing . The aim of this study was to explore the clinical effects of a treatment strategy for chronic periodontitis based on a combination of same-day full-mouth root planing and subgingival chlorhexidine varnish administration . METHODS A r and omized , controlled , single-blind , parallel trial was conducted on 12 chronic periodontitis patients . The control group received oral hygiene instructions and same-day full-mouth root planing . The test group received the same instructions and treatment ; however , all pockets were additionally disinfected using a chlorhexidine varnish . Clinical response parameters were recorded at baseline and subsequently after 1 and 3 months . RESULTS Both treatment strategies showed significant reductions in probing depth at both follow-up visits in comparison with baseline levels ( P < or=0.029 ) . Yet , at 3 months , initially diseased sites of the test group showed significant additional pocket reductions between 0.70 and 1.37 mm ( P < or=0.021 ) . Furthermore , a significant additive clinical attachment gain of 1.17 mm ( P = 0.049 ) for initially deep pockets ( > or=7 mm ) was found favoring the test group . CONCLUSION These preliminary findings suggest that the outcome of same-day full-mouth root planing may benefit from the subgingival administration of a highly concentrated chlorhexidine varnish The present study was performed to assess and compare the clinical healing and the microbiological findings following local application of metronidazole or tetracycline to augment subgingival scaling in previously untreated adult periodontitis sites . Eighteen patients with moderate to severe adult periodontitis at single-rooted teeth were selected . In each patient , 3 interproximal sites having comparable root anatomy , probing depth > or = 5 mm and bleeding on probing were r and omly assigned to 1 of 3 treatment groups : 1 ) two sessions of subgingival scaling and root planing ; 2 ) similar to 1 , with each treatment supplemented with a 25 % metronidazole sustained release gel ; 3 ) similar to 1 with each treatment supplemented with a 3 % tetracycline ointment . The treatments were performed by 1 operator and the clinical variables probing depth , attachment level , and bleeding on probing were evaluated at baseline , 3 months and 6 months by a second blinded examiner . The microbiological findings were evaluated using a commercial test kit . The average probing depth reduction for the 3 groups at 6 months was 1.5 mm and the average gain of clinical attachment was 0.8 mm . There were no significant differences between the effects following topical application of the metronidazole gel or the tetracycline ointment . Scaling and root planing alone appeared as effective as the drug augmented regimens , although there was a weak but non-significant tendency for better results in sites treated with the antibiotic drugs . Actinobacillus actinomycetemcomitans was generally not detected ; Prevotella intermedia was not significantly reduced , while Porphyromonas gingivalis was significantly reduced in all treatment groups . It was concluded that the augmentative effect of the metronidazole gel and the tetracycline ointment was comparable but small compared to scaling and root planing alone . The clinical importance of such small augmentation effects should be further evaluated BACKGROUND Currently , several local antimicrobial delivery systems are available to periodontists . The aim of this 6-month follow-up parallel study was to evaluate the efficacy of three commercially available local delivery systems as adjuncts to scaling and root planing in the treatment of sites with persistent periodontal lesions . METHODS Seventy-nine patients with 4 pockets > or = 5 mm and bleeding on probing and /or suppuration were r and omized into 4 treatment groups which included : scaling and root planing alone ( S ) ( 20 patients ) , or in conjunction with the application of 25 % tetracycline fibers ( S+Tet ) ( 19 patients ) , or 2 % minocycline gel ( S+Min ) ( 21 patients ) , or 25 % metronidazole gel ( S+Met ) ( 19 patients ) . Clinical measurements were taken at baseline , 6 weeks , 3 months , and 6 months after antimicrobial application . Treatments were applied using the distributors ' recommended protocol s. RESULTS All 4 therapies result ed in significant improvements from baseline in probing depth , attachment level , bleeding on probing , and the Modified Gingival Index ( MGI ) scores . The improvements in clinical parameters were greater in all 3 adjunctive treatment groups than scaling and root planing alone . The mean probing depth reductions at 6 months were : scaling + tetracycline = 1.38 mm ; scaling + metronidazole = 0.93 mm ; scaling + minocycline = 1.10 mm ; and scaling alone = 0.71 mm . The probing depth reduction at all time points was significantly greater in the scaling plus tetracycline fiber group than the scaling and root planing alone group ( P<0.01 ) . There was also a significant improvement for scaling plus tetracycline fiber application over scaling and metronidazole at both 6 weeks and 3 months , although this did not remain significant at the 6-month visit . While the frequency of sites with suppuration was markedly reduced following all antimicrobial treatments , the most effective reductions were seen in the scaling plus tetracycline fiber group , followed by the minocycline group . CONCLUSIONS Although all 3 locally applied antimicrobial systems seem to offer some benefit over scaling and root planing alone , a treatment regimen of scaling and root planing plus tetracycline fiber placement gave the greatest reduction in probing depth over the 6 months after treatment BACKGROUND Several antibacterial agents have been studied as a means to produce bactericidal or bacteriostatic activity as an adjunct to mechanical treatment of periodontal disease . The primary purpose of this study was to evaluate the efficacy of tetracycline strips administered singly or in multiples in conjunction with root planing , versus root planing alone , or to an untreated control . Secondary purpose s were to compare gingival crevicular fluid ( GCF ) volume and GCF concentrations of tetracycline in pockets treated with strips ; to evaluate strip insertion time ; and to compare ease of placement for single or multiple strips . METHODS Using a 4-quadrant design , 4 test teeth in 24 patients were treated with either root planing and single strip application ; root planing and multiple strip application ; root planing alone ; or an untreated control . RESULTS Single and multiple strip placement result ed in a significant reduction in probing depth ( P = 0.033 ) compared to root planing and untreated groups . The multiple strip group significantly decreased bleeding on probing ( P = 0.05 ) compared to all other treatment groups . There was no treatment effect on GCF ; however , there was a significant reduction in the GCF volume over time ( P = 0.001 ) . The time required for placement was , on average , 1.9 minutes for single strips and 3.25 minutes for multiple strips . CONCLUSIONS Our data suggest that multiple strips are superior to a single strip in reducing bleeding on probing , and that local delivery of tetracycline is superior to root planing alone in reducing probing depth AIM To determine whether adjunctive metronidazole therapy would compensate for the poorer treatment response to scaling and root planing reported in smokers . METHOD A single-blind , r and omised clinical trial of 28 smokers and 56 non-smokers , stratified for periodontitis disease severity and r and omly allocated to 3 treatment groups : ( 1 ) Scaling and root planing using an ultrasonic scaler with local anaesthesia ( SRP ) , ( 2 ) SRP+ metronidazole tabs 200 mg tds for 7 days , ( 3 ) SRP + 2 subgingival applications of 25 % metronidazole gel . Probing depths ( PD ) and attachment levels ( AL ) were recorded with a Florida probe at baseline , 2 months and 6 months post treatment by a single examiner who was unaware of the treatment modality . Results were analysed for all sites with baseline probing depths equal to or greater than Florida probe recordings of 4.6 mm using analysis of variance . RESULTS Reductions in probing depth at 6 months were significantly less ( p < 0.001 ) in the smokers ( mean 1.23 mm , 95 % confidence intervals = 1.05 to 1.40 mm ) than in the non-smokers ( 1.92 , 1.75 to 2.09 mm ) . Attachment level gains were approximately 0.55 mm and there was no statistically significant difference between smokers and non-smokers . There were no differences in any clinical measure in response to the three treatment regimens at 2 or 6 months for either smokers or non-smokers . A reduction in the proportion of spirochaetes was observed at 6 months which was less in smokers than in non-smokers ( p = 0.034 ) . Multiple linear regression analysis on probing depth at 6 months demonstrated that smoking was a significant explanatory factor ( p < 0.001 ) for poor treatment outcome , whilst the presence or absence of adjunctive metronidazole was not ( p = 0.620 ) . CONCLUSION This study confirms that smokers have a poorer treatment response to SRP , regardless of the application of either systemic or locally applied adjunctive metronidazole BACKGROUND Tetracyclines have been extensively used as adjunctives to conventional periodontal therapy . Emergence of resistant strains , however , has been reported . This study evaluated longitudinally the tetracycline resistance patterns of the subgingival microbiota of periodontitis subjects treated with systemic or local tetracycline therapy+scaling and root planing ( SRP ) . METHODS Thirty chronic periodontitis patients were r and omly assigned to three groups : SRP+500 mg of systemic tetracycline twice/day for 14 days ; SRP alone and SRP+tetracycline fibers ( Actsite ) at four selected sites for 10 days . Subgingival plaque sample s were obtained from four sites with probing pocket depths ( PPD ) > or = 6 mm in each patient at baseline , 1 week , 3 , 6 and 12 months post-therapy . Sample s were dispersed and diluted in pre-reduced anaerobically sterilized Ringer 's solution , plated on Trypticase Soy Agar (TSA)+5 % blood with or without 4 microg/ml of tetracycline and incubated anaerobically for 10 days . The percentage of resistant microorganisms were determined and the isolates identified by DNA probes and the checkerboard method . Significance of differences among and within groups over time was sought using the Kruskal-Wallis and Friedman tests , respectively . RESULTS The percentage of resistant microorganisms increased significantly at 1 week in the tetracycline groups , but dropped to baseline levels over time . The SRP+Actsite group presented the lowest proportions of resistant species at 6 and 12 months . No significant changes were observed in the SRP group . The predominant tetracycline-resistant species included Streptococcus spp . , Veillonela parvula , Peptostreptococcus micros , Prevotella intermedia , Gemella morbillorum and Actinobacillus actinomycetemcomitans ( Aa ) . A high percentage of sites with resistant Aa , Porphyromonas gingivalis and Tanerella forsythensis was observed in all groups at baseline . However , T. forsythensis was not detected in any group and P. gingivalis was not present in the SRP+Actsite group at 1 year post-therapy . Aa was still frequently detected in all groups after therapy . However , the greatest reduction was observed in the SRP+Actsite group . CONCLUSION Local or systemically administered tetracycline results in transitory selection of subgingival species intrinsically resistant to this drug . Although the percentage of sites harboring periodontal pathogens resistant to tetracycline were quite elevated in this population , both therapies were effective in reducing their prevalence over time AIM In the present 6-month multicentre trial , the outcome of 2 different approaches to non-surgical treatment of chronic periodontitis , both involving the use of a locally delivered controlled-release doxycycline , was evaluated . MATERIAL AND METHODS 105 adult patients with moderately advanced chronic periodontitis from 3 centres participated in the trial . Each patient had to present with at least 8 periodontal sites in 2 jaw quadrants with a probing pocket depth ( PPD ) of > or = 5 mm and bleeding following pocket probing ( BoP ) , out of which at least 2 sites had to be > or = 7 mm and a further 2 sites > or = 6 mm . Following a baseline examination , including assessment s of plaque , PPD , clinical attachment level ( CAL ) and BoP , careful instruction in oral hygiene was given . The patients were then r and omly assigned to one of two treatment groups : scaling/root planing ( SRP ) with local analgesia or debridement ( supra- and subgingival ultrasonic instrumentation without analgesia ) . The " SRP " group received a single episode of full-mouth supra-/subgingival scaling and root planing under local analgesia . In addition , at a 3-month recall visit , a full-mouth supra-/subgingival debridement using ultrasonic instrumentation was provided . This was followed by subgingival application of an 8.5 % w/w doxycycline polymer at sites with a remaining PPD of > or = 5 mm . The patients of the " debridement " group were initially subjected to a 45-minute full-mouth debridement with the use of an ultrasonic instrument and without administration of local analgesia , and followed by application of doxycycline in sites with a PPD of > or = 5 mm . At month 3 , sites with a remaining PPD of > or = 5 mm were subjected to scaling and root planing . Clinical re-examinations were performed at 3 and 6 months . RESULTS At 3 months , the proportion of sites showing PPD of < or = 4 mm was significantly higher in the " debridement " group than in the " SRP " group ( 58 % versus 50 % ; p<0.05 ) . The CAL gain at 3 months amounted to 0.8 mm in the " debridement " group and 0.5 mm in the " SRP " group ( p=0.064 ) . The proportion of sites demonstrating a clinical ly significant CAL gain ( > or = 2 mm ) was higher in the " debridement " group than in the " SRP " group ( 38 % versus 30 % ; p<0.05 ) . At the 6-month examination , no statistically significant differences in PPD or CAL were found between the two treatment groups . BoP was significantly lower for the " debridement " group than for the " SRP " group ( p<0.001 ) both at 3- and 6 months . The mean total treatment time ( baseline and 3-month ) for the " SRP " patients was 3:11 h , compared to 2:00 h for the patients in the " debridement " group ( p<0.001 ) . CONCLUSION The results indicate that simplified subgingival instrumentation combined with local application of doxycycline in deep periodontal sites can be considered as a justified approach for non-surgical treatment of chronic periodontitis AIM The aim of this study was to evaluate and compare the efficacy of subgingivally delivered 10 % doxycycline hyclate and xanthan based chlorhexidine gels when used as an adjunct to scaling and root planing ( SRP ) in the treatment of chronic periodontitis . METHODS AND MATERIAL S A r and omized , controlled , single center study was conducted involving 90 sites in 30 patients suffering from moderate to advanced chronic periodontitis . Each patient contributed three sites which were r and omized to three treatment groups : SRP + insertion of doxycycline gel [ SRP+DH ] , SRP + insertion of chlorhexidine gel [ SRP+CHX ] ) , and SRP alone [ SRP ] . Gingival index ( GI ) , plaque index ( PI ) , probing pocket depth ( PPD ) , and clinical attachment level ( CAL ) were recorded at baseline , 1 month , and 3 months post therapy . RESULTS All treatments showed significant reductions in PPD and CAL at 1 and 3 months when compared to baseline values ( p<0.001 ) . At 3 months , sites treated with SRP+DH and SRP+CHX showed an additional reduction in PPD of 0.86 + /- 1.0 mm and 0.66 + /- 1.58 mm , respectively , significantly greater than SRP alone ( p<0.02 ) . Differences in mean PPD reduction between SRP+DH and SRP+CHX were not significant ( p=0.46 ) . At 3 months , differences in relative CAL between both SRP+DH ( 0.80 + /- 0.92 ) and SRP+CHX ( 0.63 + /- 1.47 ) and SRP alone were statistically significant ( p<0.02 ) . Differences in relative CAL between SRP+DH and SRP+CHX were not significant ( p=0.54 ) . CONCLUSION The results suggest treatment with 10 % doxycycline hyclate and xanthan based chlorhexidine gels as an adjunct to SRP improves PPD and CAL patients with periodontitis compared to SRP alone . CLINICAL SIGNIFICANCE The use of local drug therapy may refocus the need for surgical periodontal therapy toward deeper pockets AIM A clinical trial was performed to determine if a single dose of subgingival minocycline has ( i ) a clinical spillover effect at adjacent and remote sites and ( ii ) an adjunctive effect to scaling and root-planing . MATERIAL S AND METHODS Each of the 15 adult subjects included in the study had to present with at least two pairs of adjacent 6 - 9 mm pockets each pair located on adjacent teeth in an interproximal space , on opposite sides of the mouth . Each study site was required to have at least 3 mm loss of attachment . Following a baseline examination including assessment s of plaque , pocket depth ( PD ) , clinical attachment levels ( CAL ) and bleeding on probing ( BOP ) , instruction in oral hygiene was given . Each subject was treated with a single episode of scaling and root-planing ( SRP ) , of approximately 90 minutes duration using ultrasonic and h and instrumentation under local anaesthetic , if indicated . This was followed by a single application of 1 mg of minocycline in the form of Minocycline Periodontal Therapeutic System ( MPTS ) into one of the four sites selected at r and om by another clinician , who also r and omly selected one of the two sites on the opposite side of the mouth to be design ated the Remote site . Clinical re-examinations were performed at 3- and 6-months . RESULTS At six months the CAL gains at the MPTS sites were statistically significantly different when compared with the Adjacent sites ( P=0.04 ) . The proportion of sites demonstrating a CAL gain ( > or = 2 mm ) was higher in the MPTS group ( 73 % ) compared with the Adjacent ( 40 % ) and Remote sites ( 53 % ) . Periodontal therapy , ( MPTS+SRP ) and ( SRP alone ) result ed in a statistically significant reduction in mean pocket depths ( P<0.01 ) . However no statistically significant differences in pocket depths were found between treatment groups over the six months of the study . The proportion of sites demonstrating a clinical ly significant reduction in PD ( > or = 2 mm ) was higher in the MPTS sites ( 80 % ) compared with the Adjacent sites ( 53 % ) and Remote sites ( 53 % ) . BOP was significantly reduced at all sites over the duration of the study except at the Adjacent sites at three months ( P<0.05 ) . CONCLUSION No apparent clinical spillover effect of minocycline was demonstrated over the six months of the study . There was a trend for greater improvement in all clinical parameters at the MPTS sites compared with the Adjacent and Remote sites except for plaque scores . This trend needs to be examined in a study with a sufficient number of subjects to allow statistical significance In this study , the clinical efficacies of systemic doxycycline ( SD ) and local doxycycline ( LD ) in the treatment of chronic periodontitis were compared . Forty-five patients were studied in 3 main groups with 5 treatments : SD alone , SD+scaling-root planing ( SD+SRP ) , LD alone , LD+SRP and SRP alone . Antibiotic-treated patients were given doxycycline treatment alone in 1 quadrant of their upper jaws , and doxycycline+SRP was given in the contralateral quadrant . The areas included at least 4 teeth with > or = 5 mm pockets . Probing depth ( PD ) , clinical attachment level , gingival index , sulcular bleeding index and plaque index values were recorded at baseline and the 7th week . The results were statistically analyzed . All of the clinical parameters were significantly reduced by all treatments ( P < or = 0.05 ) . The SD and LD treatments alone provided significant clinical healings . The significant differences among the groups were only in PD at the 7th week . The LD treatment provided significantly higher PD reduction than the SD treatment ( P < or = 0.05 ) . No significant difference was found between the SD+SRP and the LD+SRP treatments . There was no significant difference between SD+SRP and SRP alone treatment ( P > 0.05 ) . The SD group showed lower PD reduction than SRP group ( P < or = 0.05 ) , while no significant difference was found between LD and SRP treatments . The LD alone treatment seemed more effective than SD alone treatment on PD reduction , but no significant difference was found between them when combined with the SRP . LD may be more preferable than SD as an adjunct to mechanical treatment since LD seems more effective than SD on PD reduction and does not have the side effects of SD The purpose of this study was to compare the efficacy of scaling and root planing ( S and RP ) alone versus tetracycline fiber therapy used adjunctively with S and RP in the treatment of localized recurrent periodontitis sites in maintenance patients . A total of 113 patients receiving regular supportive periodontal therapy ( SPT ) were treated with whole mouth S and RP . Two non-adjacent sites in separate quadrants were selected in each patient for monitoring based on criteria that the sites were 5 to 8 mm deep and had a history of bleeding on probing . The chosen sites were r and omly assigned to one of the two treatment groups . Probing depth ( PD ) , bleeding on probing ( BOP ) , and clinical attachment level ( CAL ) were measured at baseline and 1 , 3 , and 6 months . At 1 , 3 and 6 months , adjunctive fiber therapy was significantly better in reducing PD ( P < 0.05 ) and reducing BOP ( P < 0.05 ) than S and RP alone . At 6 months , fiber therapy was significantly better in promoting clinical attachment gain ( P < 0.05 ) than S and RP alone . Overall , these results indicate that fiber therapy significantly enhanced the effectiveness of S and RP in the management of localized recurrent periodontitis sites , in patients receiving regular supportive periodontal treatment OBJECTIVE The objective of this study was to investigate the association between the antimicrobial and clinical efficacy of minocycline hydrochloride microspheres when used adjunctively with scaling and root planing . METHODS 127 subjects with moderate-to-advanced chronic periodontitis were r and omly assigned to receive either minocycline microspheres plus scaling and root planing ( n = 62 ) or scaling and root planing alone ( n = 65 ) . Deoxyribose nucleic acid analysis and clinical data were obtained at baseline and 30 days after treatment . End points included changes in the mean sum of red complex bacteria , pocket depth , number of deep pockets , bleeding on probing , and clinical attachment level from baseline to day 30 . Regression analysis determined the association between microbiological and clinical efficacy . RESULTS Minocycline microspheres plus scaling and root planing reduced pocket depth , the number of deep pockets and bleeding on probing , and increased clinical attachment level significantly more than scaling and root planing alone ( p < 0.05 ) . Comparing minocycline microspheres plus scaling and root planing with scaling and root planing alone , the number needed to treat for a 2 mm pocket depth reduction difference was 6.5 . Pocket depth reduction correlated significantly with a decrease in the numbers and proportions of red complex bacteria . Minocycline microspheres significantly improved all clinical parameters compared to scaling and root planing alone . CONCLUSIONS The addition of minocycline microspheres to scaling and root planing led to a greater reduction in the proportions and numbers of red complex bacteria . The reduction in pocket depth was significantly correlated with the reduction of the proportions and numbers of red complex bacteria . Additionally , there were statistically greater improvements in all clinical parameters examined BACKGROUND S/ AIMS The aim of our study was to evaluate the clinical , radiological and microbiological response to the local delivery of tetracycline ( TE ) of sites with persistent periodontal lesions . MATERIAL S AND METHODS The study was conducted in a split-mouth design . Nineteen patients with at least four bilateral pockets 4 - 5 mm and bleeding on probing ( BOP ) were treated with scaling and root planing ( SRP ) plus TE fibres ( test sites ) or with SRP alone ( control sites ) . Clinical and radiological measurements were taken at baseline , 6 months and 12 months post-operatively . Subgingival plaque sample s were collected at baseline , at fibres removal , 6 and 12 months following treatment and analysed by polymerase chain reaction . RESULTS Both treatments yielded a statistically significant ( p<0.05 ) reduction of probing depth ( 2.05 and 1.21 mm ) , gain of clinical attachment level ( 1.71 and 0.53 mm ) and reduction of BOP scores ( 23.68 % and 57.89 % ) for TE and SRP groups , respectively , when comparing 12-month data with baseline . The differences between two groups were significant . The prevalence of Treponema denticola and Bacteroides forsythus decreased after therapy in both groups but only in the test sites Actinobacillus actinomycetemcomitans and Prevotella intermedia were not yield detected . The pathogens could be eliminated from five periodontal pockets by SRP alone , while 21 TE sites were not recolonized at 12 months . CONCLUSIONS SRP plus TE fibres gave the greatest advantage in the treatment of periodontal persistent lesions at least 12 months following treatment The present studies evaluated the efficacy of a controlled-release biodegradable chlorhexidine ( CHX ) ( 2.5 mg ) chip when used as an adjunct to scaling and root planing on reducing probing depth ( PD ) and improving clinical attachment level ( CAL ) in adult periodontitis . Two double-blind , r and omized , placebo-controlled multi-center clinical trials ( 5 centers each ) were conducted ; pooled data are reported from all 10 centers ( 447 patients ) . At baseline , following 1 hour of scaling and root planing ( SRP ) in patients free of supragingival calculus , the chip was placed in target sites with PD 5 to 8 mm which bled on probing . Chip placement was repeated at 3 and /or 6 months if PD remained > or = 5 mm . Study sites in active chip subjects received either CHX chip plus SRP or SRP alone ( to maintain study blind ) . Sites in placebo chip subjects received either placebo chip plus SRP or SRP alone . Examinations were performed at baseline ; 7 days ; 6 weeks ; and 3 , 6 , and 9 months . At 9 months significant reductions from baseline favoring the chlorhexidine chip compared with both control treatments were observed with respect to PD ( chlorhexidine chip plus SRP , 0.95 + /- 0.05 mm ; SRP alone , 0.65 + /- 0.05 mm , P < 0.001 ; placebo chip plus SRP , 0.69 + /- 0.05 mm , P < 0.001 ) and CAL ( chlorhexidine chip plus SRP , 0.75 + /- 0.06 mm ; SRP alone , 0.58 + /- 0.06 mm , P < 0.05 ; placebo chip plus SRP , 0.55 + /- 0.06 mm , P < 0.05 ) . The proportion of patients who evidence d a PD reduction from baseline of 2 mm or more at 9 months was significantly greater in the chlorhexidine chip group ( 19 % ) compared with SRP controls ( 8 % ) ( P < 0.05 ) . Adverse effects were minor and transient toothache , including pain , tenderness , aching , throbbing , soreness , discomfort , or sensitivity was the only adverse effect that was higher in the chlorhexidine group as compared to placebo ( P = 0.042 ) . These data demonstrate that the adjunctive use of the chlorhexidine chip results in a significant reduction of PD when compared with both SRP alone or the adjunctive use of a placebo chip . These multi-center r and omized control trials suggest that the chlorhexidine chip is a safe and effective adjunctive chemotherapy for the treatment of adult periodontitis BACKGROUND , AIMS Conventional treatment of chronic periodontitis involves mechanical debridement of periodontal pockets . Recently , subgingival antimicrobials have been used adjunctively following such debridement . This 2-centre study compared the clinical effects of subgingival scaling ( SRP ) with SRP plus subgingival application of 25 % metronidazole gel , Elyzol ( SRP+gel ) , in patients with chronic adult periodontitis . METHOD Voluntary informed written consent was obtained from 45 subjects at the Eastman ( mean age 46 , range 34 - 63 ) and 43 subjects at RAF Halton ( mean age 47 , range 34 - 71 ) who participated in this blind , r and omised split-mouth design study . All had at least 2 sites in each quadrant with probing pocket depth ( PPD ) > or = 5 mm . PPD , bleeding on probing ( BOP ) , and clinical probing attachment levels ( CAL ) measured using a stent , were recorded at baseline and at 1 , 3 , 6 and 9 months post-therapy . After subgingival scaling of all quadrants , 2 quadrants were r and omly selected to be treated with metronidazole gel . RESULTS A paired t-test on baseline values showed no bias between groups . Both treatments effectively reduced the signs of periodontitis . At each follow-up visit , reduction in PPD , CAL and BOP after the combined treatment was greater than for SRP alone . Paired t-tests showed that the improvement in the SRP+gel group was statistically significantly better ( p<0.001 ) than for SRP alone ( mean 0.5 + /- 0.6 mm . 95 % CI 0.4 - 0.6 mm . ) Similarly , the % of sites which improved to a final pocket depth of < or = 3 mm and the % of sites which improved over the 9 months of the study by as much as > or = 2 mm were greater for SRP+gel than for SRP alone . CONCLUSIONS At the end of the study , the mean reductions for PPD were 1.0 mm ( SRP ) compared to 1.5 mm ( SRP+gel ) , and for CAL they were 0.4 mm ( SRP ) compared to 0.8 mm ( SRP+gel ) , with mean difference for CAL between treatments of 0.4 + /- 0.6 mm ( 95 % confidence intervals of 0.3 - 0.6 mm ) . The combination therapy of SRP+gel was superior to the conventional treatment of SRP alone , and these differences were maintained for 9 months The objectives of the present study were to establish in a long-term investigation the safety as well as the clinical and microbiological efficacy of scaling and rootplaning combined with local application of 2 % minocycline hydrochloride-gel versus placebo-gel in patients with moderate to severe chronic adult periodontitis . This was an 18 months , r and omized , double-blind , parallel , comparative study , in which 20 healthy patients with moderate to severe chronic periodontitis participated . At baseline , all patients received professional oral hygiene-instruction and supra- and subgingival scaling and root planing . The minocycline-gel was applied subgingivally baseline , 2 weeks , 1 , 3 , 6 , 9 and 12 months . Microbiological evaluation was carried out using DMDx to identify the following bacteria : Porphyromonas gingivalis , Prevotella intermedia , Actinobacillus actinomycetemcomitans , Campylobacter rectus , Fusobacterium nucleatum and Treponema denticola . In addition st and ard microbiological techniques were used for the detection of P. gingivalis , P. intermedia , P. micros , A. actinomycetemcomitans , C. rectus , F. nucleatum , C. albicans and Enterobacteriaceae . Results showed a statistically significant improvement for all clinical parameters irrespective of the treatment modality . No differences were observed between test and control with regard to probing depth and attachment level . The DMDx data showed a significant reduction in both the numbers and the prevalence over the 15 months period , but no significant difference between groups . Culture data showed that at baseline two-third were positive for P. gingivalis and P. intermedia . Analysis over the 18 month period showed no significant difference between the two treatment modalities . C. albicans and Enterobacteriaceae were detected only in small proportions at each time interval in a limited number of patients . No adverse reactions were observed during the trial period . The present patient group responded favourably to scaling and rootplaning , but did not benefit from an effect of local of minocycline . Subgingival debridement in combination with oral hygiene instruction by itself has been shown to be effective . It remains to be studied whether local application of minocycline can be effective as an adjunct to mechanical therapy in sites that respond poorly to conventional treatment BACKGROUND Alternative regimens using subgingival antimicrobials compared to conventional periodontal maintenance ( PM ) may lead to more efficient protocol s. The purpose of this study was to evaluate treatment time and clinical and radiographic outcomes in 2 periodontitis cohorts , one receiving conventional PM and the other receiving scaling and root planing ( SRP ) and multiple doses of subgingival minocycline . METHODS Moderate to advanced chronic periodontitis patients were concurrently treated with either : 1 ) scaling and root planing and 4 subgingival doses of minocycline microspheres in all > or = 5 mm pockets over a 6-month period ( RP/M ; n = 24 patients ) ; or 2 ) conventional 3-month periodontal maintenance ( PM ; n = 24 patients ) . Clinical and radiographic measurements , including probing depth ( PD ) , clinical attachment level ( CAL ) , and interproximal bone height ( BH ) , were analyzed in 2 premolar/molar interproximal > or = 5 mm pockets at baseline and 1 year using paired t tests , analysis of variance , chi-square analysis , and correlation coefficients . RESULTS Baseline clinical and radiographic data were similar between RP/M and PM patients . Probing depths showed greater mean improvement in RP/M ( 0.9 + /- 0.1 versus 0.4 + /- 0.1 mm , P = 0.02 ) , with 25 % of subjects in RP/M gaining > or = 2 mm compared to 4.2 % in PM ( differences were statistically significant ) . The mean loss in bone height and percent subjects losing bone height were less in RP/M ( 0.05 + /- 0.05 mm ; 12.5 % ) than PM ( 0.09 + /- 0.08 mm ; 16.7 % ) , but bone height differences were not statistically significant . A subset of RP/M molar furcation sites responded with similar PD reduction and no BH loss over 1 year . While cross-sectional RP/M data between CAL and BH , or PD and CAL were highly correlated , changes over 1 year were not correlated among any of these parameters . CONCLUSIONS Scaling and root planing and subgingival minocycline in experimental sites took little time ( < 5 minutes/appointment ) , but result ed in more probing depth reduction and less frequent bone height loss than conventional periodontal maintenance AIM The aim of this r and omised , split-mouth , single-blind study was to determine the efficacy of controlled-release delivery of chlorhexidine gluconate 2.5 mg ( PerioChip ) in patients with residual bleeding pockets ( > 5 mm ) at least 3 months following oral hygiene and root debridement phase therapy . MATERIAL AND METHODS 26 patients ( non-smokers ) were screened and potential study sites identified . Clinical parameters recorded at baseline and all subsequent visits were plaque index ( PI ) , pocket probing depth ( PPD ) , bleeding index ( BI ) and clinical attachment level ( CAL ) . All study sites were debrided using ultrasonic instrumentation . PerioChips ( PC ) were placed in the selected sites of two quadrants ( left or right ) whilst identified sites in the remaining quadrants were left without adjunctive antimicrobial treatment . Clinical measurements were made at follow-up visits after 1 , 3 and 6 months . Mean changes from baseline in PPD , BI and CAL were calculated with the patient as the experimental unit and comparability between the treatments was determined using t-tests . RESULTS At baseline there were no significant differences between PC and control sites for mean PI , PD , BI or CAL . The mean ( SE ) reductions in PPD for PC and control treatments were : 0.47 ( 0.1 ) , 0.46 ( 0.1 ) ; 0.76 ( 0.1 ) , 0.55 ( 0.1 ) ; 0.78 ( 0.1 ) , 0.45 ( 0.1 ) for months 1 , 3 and 6 respectively . Only at month 6 did the difference between treatments approach statistical significance ( p=0.06 ) . Mean ( SE ) reductions in CAL over the same periods were : 0.17 ( 0.1 ) , 0.04 ( 0.08 ) ; 0.38 ( 0.1 ) , 0.21 ( 0.1 ) ; 0.43 ( 0.1 ) , 0.15 ( 0.09 ) p=0.048 . Mean ( SE ) reduction in BI between PC and control treatments only reached statistical significance at 6 months : 1.08 ( 0.1 ) , 0.59 ( 0.1 ) p=0.05 . CONCLUSION These data suggest that PerioChip is beneficial for patients on maintenance therapy although the benefit is not apparent until 6 months after placement AIM This study was carried out to investigate the effect of 2 applications of a metronidazole 25 % dental gel as adjunctive therapy to subgingival scaling with root planing . METHOD 59 of the original collective of 64 patients with adult periodontitis were observed for a 9-month period . This r and omised single-blind study was carried out in split-mouth design . Each patient had to have at least 2 pockets with a probing depth of > or = 5 mm in each quadrant . The clinical parameters , pocket probing depth ( PPD ) , attachment level ( AL ) and bleeding on probing ( BOP ) , were recorded at all teeth on days 0 , 91 , 175 and 259 ; in addition , subgingival plaque sample s taken from 45 patients were analysed by means of dark-field microscopy . Therapy comprised subgingival scaling and root planing ( SRP ) of all quadrants and additional application of metronidazole 25 % , dental gel in 2 r and omly selected quadrants ( SRP+Metro ) . Treatment was confined to teeth with a baseline PPD of > or = 5 mm . Average PPD and AL and the incidence of BOP were computed for all pockets with a baseline PPD of > or = 5 mm , and the 2 methods compared . The main efficacy variable for evaluation of the 2 treatments was the difference in PPD on day 259 . RESULTS Comparison of the 2 treatments revealed a statistically significant improvement in the clinical parameters for both treatment methods over the study period . Between baseline and day 259 , significant differences in PPD ( SRP+Metro : from 6.00 to 4.63 mm , SRP : from 6.02 to 4.83 mm ) and BOP ( SRP+Metro : from 67 to 31 % , SRP : from 64 to 36 % ) were observed between the 2 treatment groups . Evaluation according to different patient groups demonstrated significant advantages of the combined therapy in previously-untreated patients , especially in female prob and s. Dark-field microscopy revealed a shift in the bacterial flora towards " healthy conditions " . CONCLUSIONS The results show that only minor advantages are to be gained from the application of a metronidazole 25 % dental gel as adjunctive therapy to subgingival scaling . The distinctly better results of combined therapy in previously-untreated patients calls for more thorough investigation BACKGROUND The aim of this clinical study was to evaluate the association of locally delivered doxycycline 10 % with scaling and root planing in the periodontal treatment of smokers during a 2-year period . METHODS Forty-eight chronic periodontitis patients , presenting a minimum of four pockets ( > or=5 mm ) that bled on probing on anterior teeth were included . Patients were r and omly assigned to receive one of the following treatments : scaling and root planing ( SRP ) and scaling and root planing followed by local application of doxycycline ( SRP-D ) . Assigned treatments were performed at baseline and at 12 months . Clinical parameters , including probing depth ( PD ) and relative attachment level ( RAL ) , were recorded at baseline ; 45 days ; 3 , 6 , and 12 months ( retreatment ) ; 45 days following retreatment ; and at 15 , 18 , and 24 months . RESULTS In initially deep pockets ( > or=7 mm ) , SRP-D showed greater PD reduction than SRP at 6 and 18 months ( mean difference between groups of 1.18 and 1.73 mm , respectively ; P < 0.05 ) and greater RAL gain in all periods after 3 months ( mean difference between groups of 1.16 , 1.99 , and 1.78 mm , at 6 , 18 , and 24 months , respectively ; P < 0.05 ) . Also , the proportion of sites showing > or=2 mm PD reduction was greater for SRP-D at 6 months ( 81.2 % x 50.8 % ; P < 0.001 ) and at 24 months ( 65.5 % x 46.5 % ; P = 0.01 ) . As for RAL gain , this proportion was 34.4 % and 18.1 % for SRP-D and SRP at 24 months , respectively ( P = 0.008 ) . CONCLUSION The use of locally delivered doxycycline may constitute an important adjunct for the active and supportive treatments of severe periodontal disease in smokers BACKGROUND Little or no data exist on the ability of subgingival application of PerioChip ( 2.5 mg chlorhexidine gluconate in a biodegradable chip ; Astra Pharmaceuticals , Westborough , MA , USA ) to suppress periodontopathic microorganisms . The present study compared the subgingival microbiota of periodontitis sites receiving the chlorhexidine chip plus scaling and root planing ( Sc/Rp ) or Sc/Rp alone . METHODS Seven males and six females , mean age 49 years , with moderate to advanced periodontitis participated in the study . In each patient , two bilateral pockets probing 6 - 7 mm were r and omly assigned to treatment by chlorhexidine chip + Sc/Rp , or by Sc/Rp alone . Subgingival placement of chlorhexidine chips was carried out according to the manufacturer 's instructions . Sc/Rp was performed with h and instruments for at least 10 min in each study tooth . Subgingival sample s were collected by paper-points at baseline , at 2 weeks and at 4 weeks post-treatment . Anaerobic culture methods were used for microbial isolation and identification . The microbiologic examination was carried out blindly . Microbiological data were evaluated by a repeated measures analysis of variance . RESULTS No statistical difference was found in total colony counts between subgingival sites treated with chlorhexidine chip + Sc/Rp and those treated with Sc/Rp alone . Also , the percentage of major periodontal pathogens ( Actinobacillus actinomycetemcomitans , Porphyromonas gingivalis and Bacteroides forsythus ) and the percentage of total periodontal pathogens ( A. actinomycetemcomitans , P. gingivalis , B. forsythus , Prevotella intermedia-group , Fusobacterium , Eubacterium , Campylobacter rectus , Peptostreptococcus micros , Eikenella corrodens , enteric rods ) were not significantly different between the chlorhexidine chip + Sc/Rp group and the Sc/Rp group . At baseline , A. actinomycetemcomitans was recovered from 4 chlorhexidine chip + Sc/Rp sites and 2 Sc/Rp sites , P. gingivalis from 5 chlorhexidine chip + Sc/Rp sites and 4 Sc/Rp sites , and B. forsythus from 9 chlorhexidine chip + Sc/Rp and 7 Sc/Rp sites . At 4 weeks , A. actinomycetemcomitans was detected in 2 chlorhexidine chip + Sc/Rp sites but not in any site receiving Sc/Rp , P. gingivalis in 2 chlorhexidine chip + Sc/Rp sites but not in any Sc/Rp site , and B. forsythus in 1 chlorhexidine chip + Sc/Rp and in 2 Sc/Rp sites . CONCLUSION The present data obtained from bilateral periodontitis lesions of 13 adults suggest that chlorhexidine chip treatment of adult periodontitis lesions provides little or no additional antimicrobial benefits compared to thorough Sc/Rp alone The purpose of this study was to compare the clinical efficacy of scaling and root planing alone versus tetracycline fiber therapy used adjunctively with scaling and root planing in the treatment of nonresponsive active periodontitis in patients under supportive periodontal therapy . Thirty patients who were receiving supportive treatment and had at least two nonadjacent periodontitis sites with a probing depth of between 4 and 8 mm and bleeding on probing , or had aspartate aminotransferase ( AST ) levels above 800 microIU in the gingival crevicular fluid in separate quadrants participated in this study . For each patient , the test sites were treated with scaling and root planing plus tetracycline fibers while the control site was treated with scaling and root planing only . Probing depths , clinical attachment levels , gingival recession , AST levels , and bleeding on probing were recorded and subgingival plaque sample s were collected at baseline and 1 , 3 , and 6 months following treatment . At 3 months after treatment , there was a reduction of bleeding on probing and probing depth , and a gain of clinical attachment in both test and control sites . The mean reduction in probing depth of the test sites was 1.38 mm and the attachment gain was 0.8 mm after 6 months . The clinical response obtained at 3 months following therapy was maintained throughout the 6-month follow-up period . However , there were no statistically significant differences between sites treated with scaling and root planing alone and those treated with combined tetracycline therapy . Most of the reductions of probing depths in the fiber group were attributed to gingival recession . The present study did not confirm the efficacy of adjunctive tetracycline fibers in treating nonresponsive sites in maintenance subjects with regard to probing depth reduction or clinical attachment gain . Reinfection of the pockets from untreated sites and extra-crevicular regions may explain the insignificant response to local tetracycline therapy The aim of this r and omized single-blind multicenter controlled clinical trial was to clinical ly evaluate the effectiveness of adjunctive local controlled drug delivery in the control of bleeding on probing in m and ibular class II furcations during maintenance care . 127 patients presenting with a class II m and ibular furcation with bleeding on probing were included in the study . They had been previously treated for periodontitis and were participating in supportive care programs in periodontal specialty practice s. Treatments consisted of scaling and root planing with oral hygiene instructions ( control ) and scaling and root planing and oral hygiene combined with local controlled drug delivery with tetracycline fibers ( test ) . The following outcomes were evaluated at baseline and 3 and 6 months after therapy at the furcation site : bleeding on controlled force probing ( BOP ) , probing pocket depth ( PD ) and clinical attachment levels ( CAL ) . Levels of oral hygiene and smoking status were also assessed . Both test and controls result ed in significant improvements of BOP and PD at 3 and 6 months . The test treatment , however , result ed in significantly better improvements : BOP decreased by 52 % in the control group and by 70 % in the test group at 3 months ; at 6 months , however , the difference was no longer significant . The test treatment result ed in a 0.5 mm greater reduction of PD than the control at 3 months , the improvement was highly significant but its duration did not extend until the 6 months evaluation . No differences were observed in terms of changes in CAL . These data indicate that addition of tetracycline fibers to mechanical therapy alone result ed in improved control of periodontal parameters during periodontal maintenance of class II m and ibular furcations . Short duration of the effect , however , requires further investigations to optimize conservative treatment of these challenging defects BACKGROUND Previous multi-center trials demonstrated the efficacy of a biodegradable chlorhexidine-gelatin chip ( CHX ) in reducing probing depth in patients with periodontitis . The present study utilized a subset of subjects from the parent study to determine if the CHX chip was effective in maintaining alveolar bone over a 9-month period . METHODS Forty-five subjects with at least four 5 to 8 mm pockets , stratified by smoking status , were enrolled in this double-blind controlled , placebo-controlled trial . Control groups received either placebo chip plus scaling and root planing ( SRP ) or SRP alone . Test group subjects received active CHX chip or SRP alone ( to maintain the blind ) . St and ardized radiographs were taken for quantitative digital subtraction radiography at baseline and 9 months . RESULTS At 9 months , 15 % of SRP treated subjects experienced loss of bone in 1 or more sites , no subject treated with active chip plus SRP lost bone ( P < 0.01 ) . At 9 months , significant differences in the change in probing depth and clinical attachment levels favoring the active chip over SRP alone or SRP plus CHX chip were also observed ( P < 0.05 ) . CONCLUSIONS These data indicate that the CHX chip , when used as an adjunct to scaling and root planing , significantly reduces loss of alveolar bone OBJECTIVE To evaluate a 2 % w/w minocycline gel ( Dentomycin ) in the treatment of older adults with chronic periodontitis . DESIGN Vehicle-controlled , split-mouth SETTING Dental Institute , St Bartholomew 's and the Royal London School of Medicine and Dentistry . SUBJECTS 22 adults ( mean age 60 years ) . INTERVENTIONS At baseline , patients received scaling and root planing . Test and placebo were applied at contralateral disease sites surrounding 22 test and 22 control teeth at baseline , and at weeks 2 and 4 . MAIN OUTCOME MEASURE Probing pocket depth , bleeding on probing and supragingival plaque measurements , and microbiological sampling , at one pocket site per tooth were undertaken at baseline , and at weeks 2 , 4 , 6 and 16 . RESULTS Microbial counts of Porphyromonas gingivalis , Prevotella intermedia and Eikenella corrodens did not change significantly over 16 weeks . No significant reductions in bleeding on probing and supragingival plaque score occurred with either gel . A larger reduction in mean pocket depth , from baseline to week 16 , was found at test ( 6.50 to 4.95 mm ; 24 % reduction ; P < 0.01 ) than at control sites ( 6.41 to 5.53 mm ; 14 % reduction ; P < 0.05 ) . CONCLUSIONS Minocycline gel administration is a useful adjunct to scaling and root planing in the treatment of older adults with periodontitis BACKGROUND The aim of the present study was to determine the effect of a chlorhexidine chip on crevicular prostagl and in E2 ( PGE2 ) levels and on the clinical and microbiological parameters of periodontitis when used as adjunctive therapy to scaling and root planing ( SRP ) in patients with chronic periodontitis . METHODS This r and omized single-blind study was carried out in parallel design . The test group received SRP plus chlorhexidine chip , whereas the control group received SRP alone . Thirty-four subjects , aged 20 to 55 years , with chronic periodontitis were recruited . Clinical indices , microbiological sample s , and gingival crevicular fluid ( GCF ) sample s were evaluated at baseline and after 1 , 3 , and 6 months . Microbiological sample s were evaluated under a light microscope . GCF PGE2 levels were determined using radioimmunoassay . RESULTS Significant improvements could be found for all clinical variables in both groups over the study period . The mean changes in probing depth obtained by SRP plus chlorhexidine chip were greater than those obtained by the SRP alone group at 3 and 6 months . In the test group , there was also significant gain in clinical attachment level at 6 months . When data were combined from all groups , significant reductions in GCF PGE2 levels and number of microorganisms were noted at all time points . However , in the test group , reduction was greater at 6 months for crevicular PGE2 level and at 3 and 6 months for proportions of spirochetes . CONCLUSION Based on the findings of this study , the chlorhexidine chip reduced GCF PGE2 levels and had positive effects on clinical parameters and subgingival flora when used as adjunctive therapy to SRP in patients with chronic periodontitis BACKGROUND Periodontitis is an inflammatory condition of tooth-supporting tissues that is usually treated by mechanical removal of plaque and microorganisms that adhere to teeth . This treatment , known as scaling and root planing , is not optimally effective . Adjunctive therapy with locally delivered antimicrobials has result ed in improved clinical outcomes such as probing depth reduction . This article reports on the efficacy and safety of locally administered microencapsulated minocycline . METHODS Seven hundred forty-eight ( 748 ) patients with moderate to advanced periodontitis were enrolled in a multi-center trial and r and omized to 1 of 3 treatment arms : 1 ) scaling and root planing ( SRP ) alone ; 2 ) SRP plus vehicle ; or 3 ) SRP plus minocycline microspheres . The primary outcome measure was probing depth reduction at 9 months . Clinical assessment s were performed at baseline and 1 , 3 , 6 , and 9 months . RESULTS Minocycline microspheres plus scaling and root planing provided substantially more probing depth reduction than either SRP alone or SRP plus vehicle . The difference reached statistical significance after the first month and was maintained throughout the trial . The improved outcome was observed to be independent of patients ' smoking status , age , gender , or baseline disease level . There was no difference in the incidence of adverse effects among treatment groups . CONCLUSIONS Scaling and root planing plus minocycline microspheres is more effective than scaling and root planing alone in reducing probing depths in periodontitis patients BACKGROUND Chemo-mechanical treatment concepts have been developed to improve the outcome of non-surgical periodontal therapy . Recently , the clinical additive value of a supersaturated chlorhexidine varnish was shown when used as an adjunct to staged scaling and root planing . The aim of this study was to investigate the clinical effects of a treatment strategy for chronic periodontitis based on a combination of same-day full-mouth root planing and subgingival chlorhexidine varnish administration . METHODS A r and omized , controlled , single-blind , parallel trial was conducted on 33 non-smoking chronic periodontitis patients . The control group received oral hygiene instructions and same-day full-mouth root planing . The test group received the same instructions and treatment ; however , all pockets were disinfected using a chlorhexidine varnish . Clinical response parameters were recorded at baseline and after 1 , 3 , and 6 months . RESULTS Both groups showed significant reductions in probing depth following therapy ( P < 0.001 ) . There was no significant difference in full-mouth probing depth between the groups at any examination point . However , when a site-specific comparison was made , additive effects were found in the test group ; an extra pocket reduction of 0.93 mm ( P = 0.044 ) for initially deep pockets ( > or=7 mm ) was found at study termination . Additive clinical attachment gains seemed to be temporary . Impermanent extra pocket reductions and clinical attachment gains were found for initially medium-deep pockets ( 4 to 6 mm ) . CONCLUSION The outcome of same-day full-mouth root planing may benefit from the subgingival administration of a highly concentrated chlorhexidine varnish , at least in terms of pocket reduction in initially deep sites ( > or=7 mm ) OBJECTIVE The aim of this r and omised , split-mouth , controlled clinical trial was to evaluate the effectiveness of a controlled-release chlorhexidine chip ( CHX chip ) as an adjunctive therapy to scaling and root planing ( SRP ) with a newly developed ultrasonic device in supportive periodontal therapy ( SPT ) . MATERIAL S AND METHODS Twenty patients with moderate-to-severe chronic periodontitis , displaying at least four sites with probing depth ( PD ) > or = 5 mm and persistent bleeding on probing ( BOP ) , were recruited for the study . The target sites were r and omly treated with either a newly developed piezo-driven ultrasonic device Vector -- or ultrasonic system ( VUS ) + CHX chip or VUS alone without adjunctive antimicrobial treatment . The clinical parameters , plaque index ( PI ) , gingival index ( GI ) , BOP , PD and clinical attachment level ( CAL ) were recorded at baseline and after 1 , 3 and 6 months . RESULTS At baseline , there were no significant differences between test and control sites for any of the investigated parameters . The average reduction of PD and improvement in CAL was greater in the VUS + CHX chip sites than in sites treated with the VUS alone at 1 , 3 and 6 months ( P < 0.05 ) . The mean reductions on PD and CAL were 0.7 and 0.6 mm for the control sites and 2.2 and 1.9 mm for the test sites , respectively . Also , the mean reduction in BOP scores were higher in the VUS + CHX chip sites compared to VUS alone at 1 , 3 and 6 months ( P < 0.05 ) . PI scores were not significantly different between VUS + CHX chip sites and VUS alone sites at any visit . CONCLUSION These data suggest that CHX chip application following SRP with the tested ultrasonic device is beneficial in improving periodontal parameters in patients on SPT The purpose of this investigation was to evaluate the clinical efficacy of controlled-release tetracycline fiber therapy in adult periodontitis patients . One hundred-twenty-two ( 122 ) adult patients from 3 dental centers were enrolled at baseline for this study . each patient provided at least one site in each of four quadrants that was > or = 5 mm and bled on probing . One or two such sites were selected as test sites and were r and omly assigned to receive one of four treatments : scaling and root planing ( S ) , scaling and root planing plus tetracycline fiber for 10 days ( SF ) , fiber therapy alone for 10 days ( F ) , or two 10-day serial fiber applications ( FF ) . After treatment , no periodontal maintenance or supportive care was provided until the end of this 12-month study . Probing depth ( PD ) , clinical attachment level ( CAL ) , plaque , and bleeding on probing ( BOP ) were measured at baseline and at 1 , 3 , 6 , 9 , and 12 months following treatment . Repeated PD and CAL measurements were taken at three locations within each site and averaged for each site . One hundred-sixteen ( 116 ) subjects completed the study . All treatments result ed in similar improvements in clinical parameters compared to baseline and were equally effective in the treatment of periodontitis as measured by probing depth reduction , clinical attachment level gain , and reduction of bleeding on probing . The clinical response , established primarily by 3 months following therapy , was generally sustained in all treatment groups for 12 months without the benefit of supportive maintenance therapy Locally delivered antibiotics are used to treat periodontitis and these agents are found to be effective in improving the treatment result . Microencapsulated minocycline hydrochloride ( Arestin ) has been tested and reported to provide significantly greater probing depth reduction in conjunction with scaling and root-planing than scaling and root-planing alone . Thus , it was suggested that the use of locally delivered antimicrobial agents should be incorporated as part of an optimal non-surgical therapeutic regimen . This paper evaluates the efficacy of the minocycline microspheres in patients with moderate to severe periodontitis in a model , which is a r and omised , evaluator-blinded study with an open-label ; four arm parallel design . The patients were selected based upon ' active ' disease , as determined by at least two teeth having one site each with pocket depth ( PD ) > or = 6 mm and with prostagl and in E2 ( PGE2 ) levels > 66.2 ng/ml in gingival crevicular fluid . The trial was of 6 months duration and used a formulation of minocycline microspheres containing 1 mg minocycline . Responses of groups receiving SRP followed by one dose per pocket of the minocycline microspheres ( SRP + MPTS ) were compared to SRP alone , MPTS alone or no treatment . There were substantially greater reductions in PD and gains in clinical attachment level ( CAL ) at each post-treatment time point in the SRP + MPTS group compared to the other treatment groups . PD reduction and gain in CAL at month 3 in the SRP + MPTS group vs. SRP alone was statistically significant . These data further support the adjunctive use of minocycline in a slow release vehicle for the treatment of periodontitis with SRP AIM The aim of this study was to evaluate the effectiveness of a controlled-released chlorhexidine chip ( CHX ) as adjunctive therapy to scaling and root planing ( SRP ) in the treatment of chronic periodontitis . MATERIAL AND METHODS Twenty patients with at least four sites with probing depth > or= 5 mm and bleeding on probing were selected . This r and omized single-blind study was carried out in parallel design . The control group received SRP alone , while the test group received SRP plus CHX chip . The clinical parameters , Plaque Index ( PlI ) , Papillary Bleeding Score ( PBS ) , Bleeding on Probing ( BOP ) , Gingival Recession ( GR ) , Probing Depth ( PD ) and Relative Attachment Level ( RAL ) , and the microbiological parameter BANA test were recorded at baseline and after 3 , 6 and 9 months . RESULTS Both groups presented significant improvements in all parameters analyzed over the study period . There were no statistically significant differences between the two groups for any parameter analyzed after 9 months , except for BOP , which was significantly reduced in the control group . The mean reductions on PD and RAL were 2.4 mm and 1.0 mm for the control group and 2.2 mm and 0.6 mm for the test group , respectively . CONCLUSION The CHX chip did not provide any clinical or microbiological benefit beyond that achieved with conventional scaling and root planning , after a 9-month period AIM Evaluation of the clinical effect of topical application of doxycycline adjunctive to non-surgical periodontal therapy . METHODS A total of 111 patients suffering from untreated or recurrent moderate to severe periodontitis at 3 different centers ( Heidelberg , Frankfurt , Nijmegen ) were treated in this double-blind split-mouth study . In each patient , 3 different treatment modalities were assigned r and omly to 3 test teeth : scaling and root planing alone ( SRP ) , SRP with subgingival vehicle control ( VEH ) , and SRP with subgingival application of a newly developed biodegradable 15 % doxycycline gel ( DOXI ) . At baseline , clinical parameters were measured at all single rooted teeth using a reference splint : PlI , PPD , relative attachment level ( RAL-V ) , GI . 3 strata were generated according to baseline PPD : ( i ) 5 - 6 mm , ( ii ) 7 - 8 mm , ( iii ) > or = 9 mm . Not more than 50 % active smokers were allowed to each stratum . 3 and 6 months after therapy re-examination was performed by examiners blinded to baseline data and test sites . The statistical comparison of RAL-V gain and PPD reduction between the treatments was based on a repeated measures ANOVA with correction according to Huynh & Feldt . The comparison of SRP versus DOXI was considered as the main study question . RESULTS 110 patients finished the 3 months and 108 the 6 months examination . The study did not show adverse effects of VEH or DOXI except for one singular inflammation that occurred 2 months after application of the doxycycline gel . DOXI provided statistically significantly more favorable PPD reduction ( SRP : -2.4+/-1.4 mm , VEH : -2.7+/-1.6 mm , DOXI : -3.1+/-1.2 mm ; SRP versus DOXI p=0.0001 , VEH versus DOXI p=0.0066 ) and RAL-V gain ( SRP : 1.6+/-1.9 mm , VEH : 1.6+/-2.2 mm , DOXI : 2.0+/-1.7 mm ; SRP versus DOXI p=0.027 , VEH versus DOXI p=0.038 ) than SRP and VEH after 6 months . CONCLUSIONS Adjunctive topical subgingival application of a biodegradable 15 % doxycycline gel was safe and provided more favorable RAL-V gain and PPD reduction than SRP alone and VEH . Thus , by use of topical doxycycline the threshold for surgical periodontal therapy might be moved toward deeper pockets BACKGROUND The main therapeutic approach for periodontal diseases is mechanical treatment of root surfaces via scaling and root planing ( SRP ) . Multicenter clinical trials have demonstrated that the adjunctive use of a chlorhexidine ( CHX ) chip is effective in improving clinical results compared to SRP alone . However , some recent studies failed to confirm these clinical results , and conflicting results were reported regarding the effects of the CHX chip on subgingival microflora . The aim of this study was to provide further data on the clinical and microbiologic effects of CHX chips when used as an adjunct to SRP . METHODS A total of 116 systemically healthy individuals with moderate to advanced periodontitis , aged 33 to 65 years , were recruited from the Departments of Periodontology of four Italian universities . For each subject , two experimental sites were chosen that had probing depths ( PD ) > or = 5 mm and bleeding on probing ( BOP ) and were located in two symmetric quadrants . These two sites were r and omized at the split-mouth level , with one receiving SRP treatment alone and the other receiving treatment with SRP plus one CHX chip ( SRP + CHX ) . PD , relative attachment level ( RAL ) , and BOP were evaluated at baseline , prior to any treatment , and after 3 and 6 months . Supragingival plaque and the modified gingival index were evaluated at baseline and after 15 days and 1 , 3 , and 6 months . Subgingival microbiologic sample s were harvested at baseline and after 15 days and 1 , 3 , and 6 months , cultured for total bacterial counts ( TBCs ) , and investigated by polymerase chain reaction analysis for the identification of eight putative periodontopathogens . RESULTS When all of the pockets were considered , the PD and RAL were significantly less at 3 and 6 months compared to the baseline scores ( P < 0.01 ) for both treatments . Moreover , the PD was reduced in the SRP + CHX treatment group compared to the SRP treatment group at 3 and 6 months , whereas the RAL was similar for both treatments at 3 months and was reduced in the SRP + CHX treatment group at 6 months . The differences in PD reductions between the treatments were 0.30 and 0.55 mm at 3 and 6 months , respectively ( P < 0.01 ) ; for the RAL gain , the differences were 0.28 and 0.64 mm , respectively ( P < 0.001 ) . The TBCs decreased significantly with both treatments . A similar , although less evident , pattern was noted when only the pockets with an initial PD > or = 7 mm were considered . The percentage of sites positive for BOP was similar between the treatments at each time point . At 15 days and 1 month , the TBC for the SRP + CHX treatment group was significantly lower than for the SRP treatment group ( P < 0.01 and P < 0.05 , respectively ) . Over time , both treatments generally reduced the percentages of sites positive for the eight putative periodontopathic bacteria , although greater reductions were seen often for the SRP + CHX treatment group . CONCLUSIONS The adjunctive use of the CHX chip result ed in a significant PD reduction and a clinical attachment gain compared to SRP alone . These results were concomitant with a significant benefit of SRP + CHX treatment on the subgingival microbiota The aim of this study was to evaluate the efficacy of 3 commercially available periodontal systems for local delivery of antibiotics as adjuncts to scaling and root planing in treatment of sites with persistent periodontal lesions following a course of scaling and root planing . Fifty-four patients with 4 pockets > or = 5 mm and bleeding on probing and /or suppuration were r and omized in 4 treatment groups including : scaling and root planing plus application of 25 % tetracycline fiber ( S + Tet ) ( 13 patients ) , scaling and root planing plus application of 2 % minocycline gel ( S + Min ) ( 14 patients ) , scaling and root planing plus application of 25 % metronidazole gel ( S + Met ) ( 14 patients ) , and scaling and root planing alone ( S ) ( 13 patients ) . Clinical measurements were taken at baseline and 6 weeks after the end of treatment periods . All treatments were applied using the distributors ' recommended protocol s and result ed in significant improvement in probing depth , attachment level , bleeding on probing and the modified gingival index ( MGI ) scores . The improvements in clinical parameters were greater in all three adjunctive treatment groups than scaling and root planing alone . The mean probing depth reductions were : S + Tet = 1.35 mm , S + Met = 0.95 mm , S + Min = 0.87 mm and S = 0.60 mm . The probing depth reduction was significantly greater in the scaling plus tetracycline fiber group than the scaling and root planing alone group ( P = 0.002 ) . The difference between groups in improvement of attachment level or bleeding on probing was not significant Scaling plus tetracycline fiber treatment result ed in the greatest reduction in the MGI scores which was significantly greater than all other groups . While the frequency of sites with suppuration was markedly reduced following all treatments , it reached zero in the scaling plus tetracycline fiber group . No serious adverse effects were observed or reported for any treatment . While all three locally applied antimicrobial systems seem to offer some benefit over scaling and root planing alone , a treatment regimen of scaling and root planing plus tetracycline fiber replacement gave the greatest advantage in the treatment of persistent periodontal lesions at least during the 6-week period following treatment The purpose of this single-blind , r and omized study was to evaluate the clinical efficacy of slow-release tetracycline fibers as an adjunct to initial periodontal therapy in moderate to advanced periodontitis patients who had no periodontal treatment before . A group of 17 patients with at least two sites in each quadrant with probing pocket depths > 5 mm that bled on probing were included in the study . After scaling and root planing , each selected site was r and omly assigned to one of two treatment groups : tetracycline fiber therapy and control group . Plaque index , gingival index , bleeding on probing , probing pocket depth , and clinical attachment level were measured at baseline and at 1 , 3 , and 7 weeks . The change from the baseline of each measurement was studied using analysis of variance with subject and treatment effects and a baseline covariate . Results of this investigation demonstrated that tetracycline fiber treatment as adjunct to scaling and root planing is effective in regard to probing pocket depth reduction and bleeding on probing . On the other h and , fiber application seems to have no beneficial effect on gain of clinical attachment level within limits of this study The safety and efficacy of a degradable , subgingivally placed drug delivery system containing 2.5 mg chlorhexidine ( CHX ) were evaluated in a r and omized , blinded , multi-center study of 118 patients with moderate periodontitis . A split-mouth design was used to compare the treatment outcomes of scaling and root planing ( SRP ) alone with the combined use of SRP and the CHX in pockets with probing depths of 5 to 8 mm . The two maxillary quadrants were used for the two treatment arms of the study . Scaling and root planing was performed at baseline only , while the CHX was inserted both at baseline and at 3 months . Clinical and safety measurements including probing depth ( PD ) , clinical attachment level ( CAL ) , and bleeding on probing ( BOP ) as well as gingivitis , plaque , and staining indices were recorded at baseline , and at 1 , 3 , and 6 months . The average PD reduction in the CHX-treated sites was significantly greater than in the sites receiving SRP alone at both 3 and 6 months with a mean difference of 0.42 mm ( P < or = 0.01 ) at 6 months . The reduction in CAL at the treated sites was greater than at the SRP sites , although the difference was statistically significant at the 6-month visit only . An analysis of patients with initial probing depths of 7 to 8 mm ( n = 56 ) revealed a significantly greater reduction in PD and CAL in those pockets treated with CHX compared to SRP at both 3 and 6 months . The mean differences between test and control sites at 6 months were 0.71 mm and 0.56 mm PD and CAL respectively Topical locally delivered minocycline is an adjunctive to non-surgical periodontal treatment , but there are few reported trials . Previous trials have reported differences between changes in probing depth in treatment and control groups , but no differences in probing attachment level . In the present study , 30 subjects were paired according to gender , age , ethnic group , smoking habits , and probing depths . Both groups received intensive oral hygiene education and root planing with local anaesthesia . Active or placebo gel was placed subgingivally at planed sites in each subject according to a double-blind protocol , immediately after instrumentation , and 2 and 4 weeks later . A periodontal examination was made with a constant force probe before instrumentation , and 6 and 12 weeks later , 2 subjects failed to complete the study , and their pairs were therefore not included in the analysis . Results were tested with analysis of covariance . Differences between groups in mean probing depth did not reach statistical significance at any visit ( baseline : test ( T ) = 5.93 mm , control ( C ) = 5.74 mm ; 6 weeks : T = 3.53 mm , C = 3.63 mm ; 12 weeks : T = 3.29 mm , C = 3.44 mm ) , but mean probing attachment levels were different ( p < 0.05 ) at both re assessment s ( baseline : T = 6.86 mm , C = 6.83 mm ; 6 weeks : T = 4.93 mm , C = 5.30 mm ; 12 weeks T = 4.91 mm , C = 5.27 mm ) . There was also a difference in the number of sites with bleeding on deep probing at 12 weeks ( p < 0.05 ) . This trial showed that adjunctive minocycline gel provided a more advantageous outcome for nonsurgical periodontal treatment in terms of probing attachment level and bleeding on deep probing . This trial was a good example of experimental , as opposed to community , design , and used limited re sources to show a clear result The present study describes results on selected clinical and microbiological parameters obtained by treatment with local ( Elyzol ) and systemic ( Flagyl ) use of metronidazole alone and /or mechanical subgingival debridement in adult periodontitis . Patients were r and omly divided into local and systemic treatment groups each comprising 5 individuals in each of whom 4 sites ( one site/ quadrant ) with a probing depth of > or = 5 mm were selected and treated with separate treatment modalities . The overall treatment design provided 6 different test groups . Groups of quadrants received : ( 1 ) scaling and root planing ; ( 2 ) local metronidazole treatment ; ( 3 ) systemic metronidazole treatment ; ( 4 ) local metronidazole combined with scaling and root planing ; ( 5 ) systemic metronidazole combined with scaling and root planing ; ( 6 ) no treatment . The microbiological and clinical effects of treatment modalities were monitored over a period of 42 days . All treatments result ed in clinical improvements ( gingivitis , probing pocket depth , attachment level ) except for the untreated group . Parallel to the clinical changes , all treatments reduced the number of total bacteria and proportions of obligately anaerobic microorganisms . Although both of the combined treatment groups responded to therapy with better resolution of infection that the pure mechanical and pure metronidazole treatments , local metronidazole in combination with scaling and root planing seems to be more effective in terms of producing both clinical and microbial improvements The purpose of this investigation was to evaluate the effect of local antibiotic therapy with metronidazole adjunctively to scaling and root planing ( SRP ) versus mechanical treatment alone . 30 maintenance- patients were included in this single-blind study . The subjects had to comply with the following criteria : 2 non-adjacent sites with a probing depth > or = 6 mm with bleeding on probing in separate quadrants , no periodontal therapy within the last 3 months , and no antibiotic therapy within the last 6 months . After r and omization , the study sites were assigned to one of the following 2 treatments : SRP plus subgingival application of metronidazole 25 % dental gel ( Elyzol ) 5x during 10 days ( test site ) or SRP alone ( control site ) . Subgingival microbiological sample s were taken prior to , and 21 days and 3 months after scaling . The sample s were analyzed with a commercial chair-side ELISA ( Evalusite ) for Porphyromonas gingivalis , Prevotella intermedia and Actinobacillus actinomycetemcomitans . Probing pocket depth ( PPD ) , attachment level ( AL ) and bleeding on probing ( BOP ) were recorded at baseline and 3 months later . PPD reduction and AL-gain were statistically significant ( p<0.001 ) after both treatments . However , there were no statistically significant differences between them . The same observation was made for BOP . P. gingivalis was reduced significantly after both treatments without statistically significant differences . P. intermedia was reduced significantly only after SRP . A. actinomycetemcomitans was not reduced significantly after either treatment . In conclusion , the repeated local application of metronidazole as an adjunct to SRP and the mechanical treatment alone showed similar clinical and microbiological effects without statistically significant differences with the exception of P. intermedia OBJECTIVE The impact of a locally delivered chlorhexidine chip ( Periochip ) on clinical and microbiological parameters of chronic periodontitis requires further documentation . The aim of the present study was to investigate the effects of the chip as an adjunct to mechanical treatment of chronic periodontitis . METHODS Fifty patients with chronic periodontitis were r and omized into two groups . The test group ( n = 25 ) received scaling and root planing and adjunctive Periochip in four pockets . The control group ( n = 25 ) received scaling and root planing only . Clinical indices ( probing depth , probing attachment level , bleeding on probing ) were assessed at baseline , three and six months . Subgingival sample s were analyzed at baseline , three weeks , three and six months after treatment for levels of eight bacterial species using " checkerboard " DNA-DNA hybridization . RESULTS The targeted difference of probing depth of 2 mm between groups was not observed . Both treatments result ed in improvement of clinical indices and non-statistically significant differences were observed between the two groups at any time point , with the exception of bleeding on probing at three months ( ANOVA , p < 0.05 ) . No major differences were observed concerning levels of important periodontal pathogens ( Mann-Whitney test , p < or = 0.05 ) . CONCLUSIONS In this small , six-month , phase 4 trial , no differences in mean probing depth reduction or " red-complex " periodontal pathogens were detected for patients with chronic periodontitis treated with adjunctive chlorhexidine chip ( single administration ) as compared to patients treated with scaling and root planing alone Introduction : Adjunctive therapy with locally delivered antimicrobials has result ed in improved clinical outcomes . The aim of this study was to evaluate the efficacy and safety of locally administered minocycline microspheres ( Arestin ™ ) in the treatment of chronic periodontitis . Material s and Methods : A total of 60 sites from 15 patients in the age group of 35 - 50 years , who had periodontal pockets measuring 5 - 8 mm and had been diagnosed with chronic periodontitis , were selected for the study . The selected groups were r and omly assigned to either the control group ( group A ) or the treatment/test group ( group B ) . Only scaling and root planing were done at the base line visit for the control sites followed by local application of Arestin ™ ( 1 mg ) . Clinical parameters such as plaque index , gingival index , and gingival bleeding index were recorded at baseline , day 30 , day 90 , and day 180 in the selected sites of both the groups . Probing pocket depth also was recorded at baseline , day 90 , and day 180 for both the groups . Results : A statistically significant reduction was observed in both groups . Group B showed better results than Group A and these differences were statistically significant . Conclusion : The results of this study clearly indicate that treatment with scaling and root planing plus minocycline microspheres ( Arestin ™ ) is more effective and safer than scaling and root planing alone in reducing the signs of chronic periodontitis BACKGROUND The objective of this trial was to measure the antimicrobial effects of a minocycline HCl microsphere ( MM ) local drug-delivery system when used as an adjunct to scaling and root planing ( SRP ) . DNA probe analysis for 40 bacteria was used to evaluate the oral bacteria of 127 subjects with moderate to advanced chronic periodontitis . METHODS Subjects were r and omly assigned to either SRP alone ( N = 65 ) or MM + SRP ( N = 62 ) . The primary endpoints of this study were changes in numbers and proportions of the red-complex bacteria ( RCB ) and the sum of Porphyromonas gingivalis , Tannerella forsythia ( formally T. forsythensis ) , and Treponema denticola relative to 40 oral bacteria at each test site from baseline to day 30 . Numbers of RCB from the five test sites were averaged to provide a value for each subject . RESULTS MM + SRP reduced the proportion of RCB by 6.49 % and the numbers by 9.4 x 10(5 ) . The reduction in RCB proportions and numbers by SRP alone ( 5.03 % and 5.1 x 10(5 ) , respectively ) was significantly less . In addition , MM + SRP reduced probing depth by 1.38 mm ( compared to 1.01 mm by SRP alone ) , bleeding on probing was reduced by 25.2 % ( compared to 13.8 % by SRP alone ) , and a clinical attachment level gain of 1.16 mm ( compared to 0.80 mm by SRP alone ) was achieved . CONCLUSION These observations support the hypothesis that RCBs are responsible for periodontal disease and that local antimicrobial therapy using MM + SRP effectively reduces numbers of RCBs and their proportions to a greater extent than SRP alone The safety and efficacy of subgingivally-applied 2 % minocycline ointment was evaluated in a r and omized , double-blind study of 103 adults with moderate to severe periodontitis . Two groups were compared ; one received the test minocycline ointment and the other a vehicle control . Both groups had scaling and root planing at baseline , after which the test or control ointments were applied with an applicator into the periodontal pockets at baseline , and at 2 , 4 , and 6 weeks . Assessment of clinical response was made by measuring probing depth and probing attachment level and gingival bleeding . These measurements were made at baseline prior to scaling and root planing , and at weeks 4 and 12 . Microbiological assessment of the subgingival flora was carried out with DNA probes at baseline , and at weeks 2 , 4 , 6 , and 12 to identify and quantify Porphyromonas gingivalis , Prevotella intermedia , and Actinobacillus actinomycetemcomitans . Subgingival minocycline ointment result ed in statistically significantly greater reduction of P. gingivalis at weeks 2 , 4 , 6 , and 12 ; P. intermedia at weeks 2 , 4 , 6 , and 12 ; and A. actinomycetemcomitans at weeks 6 and 12 . Probing depth reductions were seen for both groups at weeks 4 and 12 ; however , this reduction was statistically significantly greater in subjects treated with minocycline ointment . Reduction in gingival index and probing attachment gain were seen in both groups , however , the differences between the groups were not statistically significant . ( ABSTRACT TRUNCATED AT 250 WORDS 46 upper and lower molars with furcation grade II involvement were selected from 16 patients with periodontal disease . The teeth were r and omly allocated to the following groups according to treatment ; ( 1 ) 4 consecutive administrations of tetracycline-immobilized cross-linked collagen film ( TC film ) at intervals of 1 week ( TC group ) ; ( 2 ) 1 root planing treatment ( RP group ) ; ( 3 ) combination treatment ( TC + RP group ) ; ( 4 ) no treatment ( control group ) . The therapeutic effects of each treatment were compared both clinical ly and microbiologically . Records of plaque index , gingival index , bleeding on probing , probing depth , probing attachment level and microscopic counts were obtained at 0 , 4 , 6 and 8 weeks . The results showed marked decreases in probing depth and density of micro-organisms in both the RP and TC + RP groups . In particular , the TC + RP group was characterized by a decreased rate of bleeding on pocket probing and an increased probing attachment gain . The above findings demonstrated that root planning is effective in the treatment of furcation involvement and that the effects are enhanced by the local administration of TC films The purpose of this study was to assess the clinical and microbiological effects of a newly developed root conditioning gel system containing tetracycline or a mixture of tetracycline and citric acid on non-surgical periodontal therapy . Sixty-four ( 64 ) single-rooted teeth with a probing depth of 4 to 6 mm were r and omly subjected to one of the following four treatments ; 1 ) root planing alone ( RP group ) ; 2 ) tetracycline-containing gel alone ( TCG group ) ; 3 ) root planing plus tetracycline-containing gel ( RP + TCG group ) ; or 4 ) root planing plus a mixture of tetracycline and citric acid-containing gel ( RP + TC-CAG group ) . Probing depth , attachment level , and tooth mobility were measured and the presence of dental plaque and gingival inflammation was recorded at baseline and after 2 , 4 , 8 , and 12 weeks . Subgingival plaque sample s from each site were collected at the same visits and examined with phase contrast microscopy for proportions of motile rods and spirochetes . Plaque index , gingival sulcus bleeding index ( SBI ) , probing depth , and attachment level decreased significantly in all groups compared to the baseline values ( P < 0.05 ) . A significant decrease in probing pocket depth was noted after 12 weeks in RP + TC-CAG group compared to the other groups ( P < 0.05 ) . Significantly more gain in attachment was detected in the RP + TC-CAG group compared to the TCG group ( P < 0.05 ) . Tooth mobility scores also decreased later in the study . A significant decrease in the proportion of motile rods was found primarily in the RP + TC-CAG group . ( ABSTRACT TRUNCATED AT 250 WORDS The release profile of chlorhexidine from the PerioChip ( Chip ) , a biodegradable local delivery system that contains 2.5 mg of chlorhexidine gluconate ( CHX ) in a cross-linked hydrolyzed gelatin matrix , into the gingival crevice , was evaluated in an in vivo , open label , single-center , 10-day pharmacokinetic study conducted on 19 volunteers with chronic adult periodontitis . Each volunteer had a single chip inserted into each of 4 selected pockets , with probing pocket depths of between 5 - 8 mm , at time 0 . Gingival crevicular fluid ( GCF ) sample s were collected using filter paper strips prior to Chip placement and at 2 h , 4 h , 24 h and 2 , 3 , 4 , 5 , 6 , 8 , and 9 days post-Chip placement . The GCF volume was measured using a calibrated Periotron 6000 . Blood sample s were collected at times 0 , 1 , 4 , 8 , 12 h and 5 days post-dosing . Urine was collected as a total 24-h specimen immediately post-dosing and 2 single sample s at time 0 , prior to dosing , and 5 days . The CHX was eluted from the paper strips and the CHX levels in GCF , blood and urine quantified using HPLC . The results indicate an initial peak concentration of CHX in the GCF at 2 h post-Chip insertion ( 2007 microg/ml ) with slightly lower concentrations of between 1300 - 1900 microg/ml being maintained over the next 96 h. The CHX concentration then progressively decreased until study conclusion with significant CHX concentrations ( mean=57 microg/ml ) still being detectable at study termination . CHX was not detectable in any of the plasma or urine sample s at any time point during the study . These results indicate that the PerioChip can maintain clinical ly effective levels of CHX in the GCF of periodontal pockets for over 1 week with no detectable systemic absorption The clinical efficacy of minocycline in a subgingival local delivery system was evaluated alone ( M ) or as an adjunct to scaling and root planing ( M + SRP ) , in comparison to scaling and root planing ( SRP ) or to no subgingival treatment ( NoTx ) in adult periodontitis . Fifty-one adult patients with > or = 7 mm periodontal pockets demonstrating the presence by culture of Porphyromonas gingivalis ( Pg ) , Prevotella intermedia ( P(i ) ) , or Actinobacillus actinomycetemcomitans ( Aa ) were r and omized into one of the above 4 treatment groups . All sites > or = 5 mm in the most diseased quadrant in each patient received the therapy . Other quadrants were not treated . All patients received st and ardized oral hygiene instructions at the beginning of the study . At 0 , 1 , 3 and 6 months following therapy the 7 mm experimental sites were evaluated for selected periodontal pathogens by DNA probe analysis . At these same time points , the plaque index , gingival index , and bleeding on probing were evaluated as well as probing depth and relative clinical attachment level which were assessed by means of an automated probe . Probing depth reduction with M + SRP was significantly greater than all other groups at one month and significantly greater than NoTx and SRP at 3 months . There were no differences in probing depth reduction among groups at 6 months . At 6 months the gain in clinical attachment level was significantly greater for SRP than for either the NoTx or M groups . The prevalence of Pg decreased significantly in the M and M + SRP groups at one month . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES The aim of this study was to investigate the clinical outcome of a subgingivally applied chlorhexidine varnish when used as an adjunct to scaling and root planing ( SRP ) in the treatment of chronic periodontitis . MATERIAL AND METHODS A r and omized controlled , single blind , parallel trial was conducted on the basis of 16 volunteers suffering from chronic periodontitis . The control group received oral hygiene instructions and was scaled and root planed in two sessions . The test group received the same instructions and treatment , however , all pockets were additionally disinfected using a chlorhexidine varnish . The gingival index , plaque index , bleeding on probing , probing pocket depth ( PPD ) and clinical attachment level ( CAL ) were recorded at baseline and subsequently after 1 and 3 months . RESULTS Both treatment strategies showed significant reductions in PPD and CAL at both follow-up visits by comparison with baseline levels ( p<0.001 ) . Yet , at study termination , combination therapy result ed in additional pocket reductions between 0.73 and 1.23 mm ( p<0.02 ) , and clinical attachment gains between 0.63 and 1.09 mm ( p<0.02 ) . CONCLUSIONS These findings suggest that a varnish-implemented strategy may improve the clinical outcome for the treatment of chronic periodontitis in comparison with SRP alone Objective : To compare clinical and microbiological responses following non-surgical treatment of moderate to advanced adult periodontitis using subgingival scaling with and without adjunctive topical or systemic metronidazole . Design : A single blind r and omised clinical trial of 90 subjects , stratified for periodontitis disease severity and smoking status , divided into three treatment groups : 1 . Subgingival scaling using ultrasonic scalers and local anaesthesia ; 2 . Subgingival scaling using ultrasonic scalers and local anaesthesia plus seven days of systemic metronidazole ( 200 mg tds ) ; 3 . Subgingival scaling using ultrasonic scalers and local anaesthesia plus two applications of 25 % metronidazole gel one week apart in all sites with probing depths more than 4 mm . Evaluations were made before treatment , and 8 weeks and 24 weeks post treatment . Main outcome measures : Probing depths , probing attachment levels and bleeding on probing were measured using a Florida probe . Bacterial morphotypes were evaluated with darkfield microscopy . Results were analysed for all sites with baseline probing depths equal to or greater than Florida probe recordings of 4.6 mm using analysis of variance . Results : 84 subjects completed the trial and the three treatment groups did not differ at baseline for any clinical parameter . Mean probing depths were reduced following treatment by greater than 1.6 mm ( Group 1 = 1.68 mm , Group 2 = 1.62 mm , Group 3 = 1.74 mm at six months post treatment ) but no significant differences were detected between treatment groups at any time point . Similarly , no significant differences were detectable between treatments for changes in mean probing attachment levels , bleeding on probing , plaque scores or proportions of bacterial morphotypes . Conclusions : This study does not support the routine use of adjunctive metronidazole in the non-surgical treatment of BACKGROUND The use of locally delivered antibacterials containing chlorhexidine ( CHX ) was proposed to improve the effectiveness of non-surgical periodontal treatment . The present multicenter r and omized study investigated the effects of a xanthan-based chlorhexidine ( Xan-CHX ) gel used as an adjunct to scaling and root planing ( SRP ) in the treatment of chronic periodontitis . METHODS Ninety-eight systemically healthy subjects with moderate to advanced periodontitis were recruited in four centers ( 59 females and 39 males ; aged 24 to 58 years ) . For each subject , two experimental sites located in two symmetric quadrants were chosen with probing depths ( PD ) > or=5 mm and positive for bleeding on probing ( BOP ) . These two sites were r and omized at the split-mouth level with one receiving a single SRP treatment and the other receiving a single SRP + Xan-CHX gel treatment . Supragingival plaque , modified gingival index , PD , clinical attachment level ( CAL ) , and BOP were evaluated at baseline ( prior to any treatment ) and after 3 and 6 months . At the same times , subgingival microbiologic sample s and gingival crevicular fluid ( GCF ) were collected for the analysis of total bacterial counts ( TBCs ) , including the identification of eight putative periodontopathogens , and alkaline phosphatase ( ALP ) activity , respectively . RESULTS The Xan-CHX treatment group showed greater improvements compared to the SRP group for PD and CAL at 3 and 6 months ( P < 0.001 ) . The differences in PD reduction between the treatments were 0.87 and 0.83 mm at 3 and 6 months , respectively ( P < 0.001 ) ; for CAL , these were 0.94 and 0.90 mm , respectively ( P < 0.001 ) . Similar behavior was seen when the subgroup of pockets > or=7 mm was considered . The percentage of sites positive for BOP was similar between the treatments at each time point . For the comparisons between the treatment groups , no differences were seen in the TBCs and GCF ALP activity at baseline and 6 months ; in contrast , slightly , but significantly , lower scores were recorded for the Xan-CHX treatment group at 3 months ( P = 0.018 and P = 0.045 , respectively ) . Moreover , greater reductions in the percentages of sites positive for the eight putative periodontopathic bacteria were generally seen for the Xan-CHX treatment group compared to SRP alone . CONCLUSIONS The adjunctive use of Xan-CHX gel promoted greater PD reductions and CAL gains compared to SRP alone . These results were concomitant with better microbiologic and biochemical outcomes when Xan-CHX gel use was added to SRP , particularly up to 3 months after treatment |
1,641 | 22,855,899 | Low to very low quality of evidence showed no significant differences between the splint therapy and control groups in terms of quality of life or depression .
None of the trial reports described effect on function . | PURPOSE The authors conducted a systematic review of all published r and omized controlled trials in which investigators compared the effectiveness of splint therapy with that of minimal or no treatment in patients with temporom and ibular disorders ( TMDs ) . | BACKGROUND The authors compared the efficacy of bilateral balanced and canine guidance ( occlusal ) splints in the treatment of temporom and ibular joint ( TMJ ) pain in subjects who experienced joint clicking with a nonoccluding splint in a double-blind , controlled r and omized clinical trial . METHODS The authors r and omly assigned 57 people with signs of disk displacement and TMJ pain into three groups according to the type of splint : bilateral balanced , canine guidance and nonoccluding . The authors followed the groups for six months using analysis of a visual analog scale ( VAS ) , palpation of the TMJ and masticatory muscles , m and ibular movements and joint sounds . They used repeated analysis of variance and a chi(2 ) test to test the hypothesis . RESULTS The type of guidance used did not influence the pain reduction , yet both occlusal splints were superior to the nonoccluding splint , on the basis of the VAS . Despite similar outcomes in relation to opening , left lateral and protrusive movements , TMJ and muscle pain on palpation , subjects who used the occlusal splints had improved clinical outcomes . The frequency of joint noises decreased over time , with no significant differences among groups . Subjects in the groups using the occlusal splints reported more comfort . CONCLUSION The type of lateral guidance did not influence the subjects ' improvement . All of the subjects had a general improvement on the VAS , though subjects in the occlusal splint groups had better results that did subjects in the nonoccluding splint group Sixty-three patients with an arthrographic diagnosis of disk displacement with reduction were r and omly assigned to three treatment groups : ( I ) onlays to maintain disk repositioning , ( II ) flat occlusal splint , or ( III ) untreated controls . Guidance for construction of the disk-repositioning onlays was established during arthrography to obtain a recaptured disk position relative to the condyle . The onlays were cemented to the teeth and maintained the new intercuspal position anteriorly and inferiorly . The flat occlusal splint was used at night only and was adjusted to maintain a maximal occlusal contact in centric relation and centric occlusion . Clinical examinations were performed before and after 6 months of treatment . The disk-repositioning onlays improved joint function and reduced joint and muscle pain when compared with the flat occlusal splint and with nontreatment . The signs and symptoms in the flat occlusal splint group were no different from those in the control group . It is concluded that disk-repositioning onlays are effective in reducing pain and dysfunction associated with disk displacement with reduction in patients in whom the disk can be maintained in a normal relationship to the condyle with the aid of such onlays . The symptoms , however , returned when the onlays were removed after 6 months ; this raises the question of whether a permanent change in the intercuspal position is necessary for long-term success Forty-five individuals with long-st and ing facial pain or headache of muscular origin were r and omly allocated into three groups . The first group was treated with acupuncture , the second group received an occlusal splint , and the third group served as controls . Both acupuncture and occlusal splint therapy significantly reduced subjective symptoms and clinical signs from the stomatognathic system . No differences between these two groups were found with regard to treatment effects . It is concluded that acupuncture is an alternative method to conventional stomatognathic treatment for individuals with craniom and ibular disorders of muscular origin OBJECTIVE To test the reliability and validity of specific instructions to classify blinding , when unclearly reported in r and omized trials , as " probably done " or " probably not done . " STUDY DESIGN AND SETTING We assessed blinding of patients , health care providers , data collectors , outcome adjudicators , and data analysts in 233 r and omized trials in duplicate and independently using detailed instructions . The response options were " definitely yes , " " probably yes , " " probably no , " and " definitely no. " We contacted authors for data verification ( 46 % response ) . For each of the five questions , we assessed reliability by calculating the agreement between the two review ers and validity by calculating the agreement between review ers ' consensus and verified data . RESULTS The percentage with unclear blinding status varied between 48.5 % ( patients ) and 84.1 % ( data analysts ) . Reliability was moderate for blinding of outcome adjudicators ( κ=0.52 ) and data analysts ( κ=0.42 ) and substantial for blinding of patients ( κ=0.71 ) , providers ( κ=0.68 ) , and data collectors ( κ=0.65 ) . The raw agreement between the consensus record and the author-verified record varied from 84.1 % ( blinding of data analysts ) to 100 % ( blinding of health care providers ) . CONCLUSION With the possible exception of blinding of data analysts , use of " probably yes " and " probably no " instead of " unclear " may enhance the assessment of blinding in trials To assess the differential efficacy of two commonly used treatments for temporom and ibular disorders ( TMD ) , intraoral appliances ( IAs ) and biofeedback ( BF ) , separately and in combination , two studies were conducted . The first study directly compared IA treatment , a combination of biofeedback and stress management ( BF/SM ) , and a waiting list control group in a sample of 80 TMD patients . Both treatments were determined to be equally credible to patients , ruling out this potential threat to the validity of the results obtained . The results demonstrated that the IA treatment was more effective than the BF/SM treatment in reducing pain after treatment , but at a 6-month follow-up the IA group significantly relapsed , especially in depression , whereas the BF/SM maintained improvements on both pain and depression and continued to improve . The second study examined the combination of IA and BF/SM in a sample of 30 TMD patients . The results of this study demonstrated that the combined treatment approach was more effective than either of the single treatments alone , particularly in pain reduction , at the 6-month follow-up . These results support the importance of using both dental and psychologic treatments to successfully treat TMD patients if treatment gains are to be maintained BACKGROUND Treatment recommendations for patients with painful temporom and ibular disorders ( TMDs ) range from conservative treatments such as physiotherapy to aggressive and irreversible treatments such as restorative reconstruction and joint surgery . METHODS The authors r and omized 200 subjects diagnosed with TMD into three groups : usual conservative , dentist-prescribed self-care treatment without any intraoral splint appliance ( UT ) ; UT plus a conventional flat-plane hard acrylic splint ( HS ) ; and UT plus a soft vinyl ( a low-cost athletic mouth guard ) splint ( SS ) . Subjects completed question naires and clinical examinations at three , six and 12 months . RESULTS The authors observed no significant differences among the groups in TMD-related pain levels or other common signs and symptoms of TMD at baseline ( BL ) or at any follow-up . The changes from BL were comparable for all three groups . The authors did not note any significant differences at any follow-up for compliance with study protocol s or for occurrences of adverse effects from either splint type . For HS versus SS , there were significant differences in rates of splint use , but these differences were not accompanied by differences in either self-reported symptoms or in clinical findings . CONCLUSIONS All patients improved over time , and traditional splint therapy offered no benefit over the SS splint therapy . Neither splint therapy provided a greater benefit than did self-care treatment without splint therapy . CLINICAL IMPLICATION S These findings suggest that clinicians who treat patients with TMD should consider prescribing low-cost nonsplint self-care therapy for most patients One hundred and ten patients , 23 males and 87 females , participated in a comparative study of the effect of acupuncture and occlusal splint therapy . All the patients exhibited signs and symptoms of craniom and ibular disorders ( CMD ) and had had pain for more than six months . The participants were r and omly assigned to three groups ; acupuncture treatment , occlusal splint therapy or control . The patients were evaluated before and immediately after treatment/control time . Ten different subjective and /or clinical assessment variables were used in the evaluation of the treatment effects . Both acupuncture and occlusal splint therapy reduced the symptoms as compared with the control group in which the symptoms remained essentially unchanged . In this short-term study , acupuncture gave better subjective results ( p < 0.001 ) than the occlusal splint therapy A r and om sample of U.S. dentists was surveyed with a mailed question naire to determine the number of splints that they fabricated over the preceding year for bruxers , patients with myofascial pain-dysfunction syndrome and patients with TM joint pain . The results indicate that a significant number of dentists treat these disorders with dental splints . Estimates are provided for the dental profession 's yearly splint output for each disorder Objectives Studies have suggested overlaps between various chronic pain conditions and painful temporom and ibular disorders ( TMDs ) . The objective of this pilot study was to assess the effectiveness of occlusal splint ( OS ) therapy on self-reported measures of pain in patients with chronic complex regional pain syndrome ( CRPS ) as compared with a nontreatment group . Methods The design was a prospect i ve r and omized controlled clinical trial . Twenty patients with CRPS were r and omly assigned to either the OS or control group . The patients in the OS group were asked to use the OS at nighttime and for 3 hours during daytime for a total of 7 weeks ; the control group had no stomatognathic intervention . The primary outcome was self-reported assessment of CRPS-related pain on numerical rating scales . Secondary outcome measures were the Temporom and ibular Index ( TMI ) , and the Short Form 36 Health Survey ( SF-36 ) . Results All patients had TMD signs and symptoms , but OS had no effect on CRPS-related pain on the numerical rating scale ( P>0.100 ) . The changes in the TMI scores over time were 16.6%±24.6 % ( improvement ) in the OS group and −21.3%±25.9 % ( impairment ) in the control group that was significant ( P=0.004 ) . There were no differences in the changes of SF-36 scores between groups ( P=0.636 ) . Discussion The use of OS for 7 weeks has no impact on CRPS-related pain but improved signs and symptoms of TMD pain . Future studies should include an active control group and evaluate if long-term changes in measures of oral health impact general health in CRPS-related pain Thirty subjects seeking treatment for masticatory muscle pain at a university-based TMJ clinic were r and omly assigned to soft-splint , palliative-treatment , and no-treatment groups . After 4 to 11 weeks of treatment , subjects were evaluated for changes from their baseline levels of symptoms , maximum pain-free opening , pain thresholds measured by a pressure algometer , and occlusal contacts . With the use of the multivariate analysis of variance and analysis of covariance , the results suggest that the soft-splint group had statistically significant improvement ( P < .01 ) , the palliative-treatment group had improvement that was not statistically significant , and the no-treatment group had a slight aggravation of symptoms . The soft-splint group had fewer occlusal contact changes assessed with shimstock compared to the palliative-treatment and no-treatment groups . The findings of this study suggest that the soft splint is an effective short-term treatment for reducing the signs and symptoms of masticatory muscle pain in patients , and the soft splint does not cause occlusal changes Two occlusal splints , the full-arch stabilization splint and the anterior midline point stop ( AMPS ) device , were evaluated for their efficiency in relieving myogenous temporom and ibular disorders ( TMD ) . One hundred and fourteen patients with myogenous TMD were distributed into 3 groups . The first group was treated with the AMPS device , the second with the stabilization splint , and the third group was the control group . Pain intensity was scored using the visual analogue scale before treatment and 1 month and 3 months after treatment . Statistical Package for the Social Sciences ( SPSS , Chicago , Ill ) and multiple comparisons tests were used to compare results before and after treatment and to compare the groups . The use of AMPS device in the first group result ed in a significant improvement after 1 month and 3 months ( P < or = .001 ) and showed a 56.66 % pain reduction . A significant improvement was also noticed in the second group ( P = .001 ) with a 47.71 % pain reduction . Although pain reduction percentage appeared more in the first group , this was not statistically significant . There was a highly significant difference between groups treated with both kinds of splints and the control group . It was concluded that both types of occlusal splints are beneficial to patients with myogenous TMD The purpose of this study was to examine the psychometric properties of the Quality of Life Index ( QLI ) ( Ferrans & Powers , 1985a ) . The sample consisted of 349 patients selected r and omly from the adult , in-unit hemodialysis patient population of Illinois . Factor analysis was used to examine the underlying factor structure . A four-factors solution best fit the data , indicating that there were four dimensions underlying the QLI : health and functioning , socioeconomic , psychological/spiritual , and family . Factor analysis of the four primary factors revealed one higher order factor , representing quality of life . Construct validity also was supported by the contrasted groups approach . As predicted , it was found that those who had higher incomes had significantly higher quality of life scores on the social and economic subscale . Support for convergent validity was provided by a strong correlation ( r = .77 ) between scores from the QLI and an assessment of life satisfaction . Findings supported the internal consistency reliability of the entire QLI ( alpha = .93 ) and the four subscales ( alphas = .87 , .82 , .90 , .77 ) A flat occlusal splint has been extensively used in the treatment of patients with temporom and ibular joint disk displacement without reduction , but no studies with untreated controls have assessed its effect . We r and omly assigned 51 patients with temporom and ibular joint pain and arthrographically verified disk displacement without reduction to be treated with a flat occlusal splint or to serve as untreated control subjects in a 12-month clinical trial . Pain symptoms disappeared in about one third of the patients in each group . Another third of the patients in the control group improved . Sixteen percent of the patients in the control group and 40 % of the patients treated with a flat occlusal splint were worse at the end than at the beginning of the study . Joint pain and muscle tenderness decreased more frequently in the nontreatment controls than in the treatment group . A statistically significant benefit of a flat occlusal splint over nontreatment control subjects could not be identified in this study of patients with painful disk displacement without reduction . The use of a flat occlusal splint in this patient group should therefore be reconsidered & NA ; Oral splints are widely used in the treatment of myofascial pain of masticatory muscles , even though their mechanism of action is unknown . The present study evaluated the therapeutic efficacy of splints using a parallel , r and omized , controlled and blind design . Following a sample size estimation , 63 subjects were recruited and assigned to 3 groups : ( 1 ) passive control : full occlusal splint worn only 30 min at each appointment : ( 2 ) active control : palatal splint worn 24 h/day : and ( 3 ) treatment : full occlusal splint worn 24 h/day . On each of 7 visits over 10 weeks , subjects rated on 100 mm visual analogue scales their pain intensity and unpleasantness at rest and after experimental mastication . The effect of pain on the quality of life was also rated on category scales . All pain ratings decreased significantly with time , and quality of life improved for all 3 groups . However , there were no significant differences between groups in any of the variables . These data suggest that the gradual reduction in the intensity and unpleasantness of myofascial pain , as well as the improvement of quality of life during the trial , was non‐specific and not related to the type of treatment To measure the reliability of chest radiographic diagnosis of acute respiratory distress syndrome ( ARDS ) we conducted an observer agreement study in which two of eight intensivists and a radiologist , blinded to one another 's interpretation , review ed 778 radiographs from 99 critically ill patients . One intensivist and a radiologist participated in pilot training . Raters made a global rating of the presence of ARDS on the basis of diffuse bilateral infiltrates . We assessed interobserver agreement in a pairwise fashion . For rater pairings in which one rater had not participated in the consensus process we found moderate levels of raw ( 0.68 to 0.80 ) , chance-corrected ( kappa 0.38 to 0.55 ) , and chance-independent ( Phi 0 . 53 to 0.75 ) agreement . The pair of raters who participated in consensus training achieved excellent to almost perfect raw ( 0.88 to 0.94 ) , chance-corrected ( kappa 0.72 to 0.88 ) , and chance-independent ( Phi 0.74 to 0.89 ) agreement . We conclude that intensivists without formal consensus training can achieve moderate levels of agreement . Consensus training is necessary to achieve the substantial or almost perfect levels of agreement optimal for the conduct of clinical trials |
1,642 | 24,947,643 | The retrieved studies showed some encouraging trends in terms of trainee satisfaction with improvement after training , but the improvements were mainly on the training tool itself .
Some tools have been proven to be construct-valid . | BACKGROUND Simulation has spread widely this last decade , especially in laparoscopic surgery , and training out of the operating room has proven its positive impact on basic skills during real laparoscopic procedures .
Few articles dealing with advanced training in laparoscopic abdominal surgery , however , have been published .
Such training may decrease learning curves in the operating room for junior surgeons with limited access to complex laparoscopic procedures as a primary operator . | Objective : To develop and vali date a comprehensive ex vivo training curriculum for laparoscopic colorectal surgery . Background : Simulators have been shown to be viable systems for teaching technical skills outside the operating room ; however , integration of simulation training into comprehensive curricula remains a major challenge in modern surgical education . Currently , no curricula have been described or vali date d for advanced laparoscopic procedures . Methods : This prospect i ve , single-blinded r and omized controlled trial allocated 25 surgical residents to receive either conventional residency training or a comprehensive training curriculum for laparoscopic colorectal surgery . The curriculum consisted of proficiency-based psychomotor training on a virtual reality simulator , cognitive training , and participation in a cadaver lab . The primary outcome measure in this study was surgical performance in the operating room . All participants performed a laparoscopic right colectomy , which was video recorded and assessed using 2 previously vali date d assessment tools . Secondary outcome measures were knowledge relating to the execution of the procedure , assessed with a multiple-choice test , and technical performance on the simulator . Results : Curricular-trained residents demonstrated superior performance in the operating room compared with conventionally trained residents ( global score 16.0 [ 14.5–18.0 ] versus 8.0 [ 6.0–14.5 ] , P = 0.030 ; number of operative steps performed 16.0 [ 12.5–17.5 ] versus 8.0 [ 6.0–14.5 ] , P = 0.021 ; procedure-specific score 71.1 [ 54.4–81.6 ] versus 51.1 [ 36.7–74.4 ] , P = 0.122 ) . Curricular-trained residents scored higher on the multiple-choice test ( 10 [ 9–11 ] versus 7.5 [ 5.3–7.5 ] , P = 0.047 ) , and outperformed conventionally trained residents in 7 of 8 tasks on the simulator . Conclusions : Participation in a comprehensive ex vivo training curriculum for laparoscopic colorectal surgery results in improved technical knowledge and improved performance in the operating room compared with conventional residency training . Reg . ID#NCT 01371136 BACKGROUND The efficacy of laparoscopy simulators remains controversial . METHODS This was a comparative prospect i ve study that evaluated the impact of simulator training on technical competence during a real surgical procedure . Residents were divided into 3 groups : the Mcgill Inanimate System for Training and Evaluation of Laparoscopic Skills ( MISTELS ) group , training on a simple simulator ; LAP Mentor group , training on a virtual simulator ; and control group . An initial evaluation was made by a vali date d score during a laparoscopic cholecystectomy . Each resident was then trained for 1 month . A second evaluation was then performed . RESULTS Before/after scores were significantly improved in the MISTELS ( P = .042 ) and LAP Mentor ( P = .026 ) groups . It was not the case in the control group . There was a better progression in the MISTELS ( P = .026 ) and LAP Mentor ( P = .007 ) groups than in the control group . There was no significant difference between the MISTELS and LAP Mentor groups . CONCLUSIONS Simulator training provides a more rapid acquisition of competence in surgical technique BACKGROUND Developing technical skill is essential to surgical training , but using the operating room for basic skill acquisition may be inefficient and expensive , especially for laparoscopic operations . This study determines if laparoscopic skills training using simulated tasks on a video-trainer improves the operative performance of surgery residents . STUDY DESIGN Second- and third-year residents ( n= 27 ) were prospect ively r and omized to receive formal laparoscopic skills training or to a control group . At baseline , residents had a vali date d global assessment of their ability to perform a laparoscopic cholecystectomy based on direct observation by three evaluators who were blinded to the residents ' r and omization status . Residents were also tested on five st and ardized video-trainer tasks . The training group practice d the video-trainer tasks as a group for 30 minutes daily for 10 days . The control group received no formal training . All residents repeated the video-trainer test and underwent a second global assessment by the same three blinded evaluators at the end of the 1-month rotation . Within-person improvement was determined ; improvement was adjusted for differences in baseline performance . RESULTS Five residents were unable to participate because of scheduling problems ; 9 residents in the training group and 13 residents in the control group completed the study . Baseline laparoscopic experience , video-trainer scores , and global assessment s were not significantly different between the two groups . The training group on average practice d the video-trainer tasks 138 times ( range 94 to 171 times ) ; the control group did not practice any task . The trained group achieved significantly greater adjusted improvement in video-trainer scores ( five of five tasks ) and global assessment s ( four of eight criteria ) over the course of the four-week curriculum , compared with controls . CONCLUSIONS Intense training improves video-eye-h and skills and translates into improved operative performance for junior surgery residents . Surgical curricula should contain laparoscopic skills training Objective : To assess the McGill Inanimate System for Training and Evaluation of Laparoscopic Skills ( MISTELS ) physical laparoscopic simulator for construct and predictive validity and for its educational utility . Summary Background Data : MISTELS is the physical simulator incorporated by the Society of American Gastrointestinal and Endoscopic Surgeons ( SAGES ) in their Fundamentals of Laparoscopic Surgery ( FLS ) program . MISTELS ’ metrics have been shown to have high interrater and test-retest reliability and to correlate with skill in animal surgery . Methods : Over 200 surgeons and trainees from 5 countries were assessed using MISTELS in a series of experiments to assess the validity of the system and to evaluate whether practicing MISTELS basic skills ( transferring ) would result in skill acquisition transferable to complex laparoscopic tasks ( suturing ) . Results : Face validity was confirmed through question ing 44 experienced laparoscopic surgeons using global rating scales . MISTELS scores increased progressively with increasing laparoscopic experience ( n = 215 , P < 0.0001 ) , and residents followed over time improved their scores ( n = 24 , P < 0.0001 ) , evidence of construct validity . Results in the host institution did not differ from 5 beta sites ( n = 215 , external validity ) . MISTELS scores correlated with a highly reliable vali date d intraoperative rating of technical skill during laparoscopic cholecystectomy ( n = 19 , r = 0.81 , P < 0.0004 ; concurrent validity ) . Novice laparoscopists were r and omized to practice /no practice of the transfer drill for 4 weeks . Improvement in intracorporeal suturing skill was significantly related to practice but not to baseline ability , career goals , or gender ( P < 0.001 ) . Conclusion : MISTELS is a practical and inexpensive inanimate system developed to teach and measure technical skills in laparoscopy . This system is reliable , valid , and a useful educational tool This study examined the impact of virtual reality ( VR ) surgical simulation on improvement of psychomotor skills relevant to the performance of laparoscopic cholecystectomy OBJECTIVE ( S ) Patient-specific simulated rehearsal ( PsR ) is a technological advance within the domain of endovascular virtual reality ( VR ) simulation . It allows incorporation of patient-specific computed tomography Digital Imaging and Communications in Medicine ( CT DICOM ) data into the simulation and subsequent rehearsal of real patient cases . This study aim ed to evaluate whether a part-task rehearsal ( PTr ) of a carotid artery stenting procedure ( CAS ) on a VR simulator is as effective as a full-task ( FTr ) preoperative run through . METHODS Medical trainees were trained in the CAS procedure and r and omised to a PTr or FTr of a challenging CAS case ( Type-II arch ) . PTr consisted of 30 min of repeated catheterisations of the common carotid artery ( CCA ) . Thereafter , both groups performed the CAS procedure in a fully functional simulated operating suite ( SOS ) with an interventional team . Technical performances were assessed using simulator-based metrics and expert ratings . Other aspects of performance were assessed using the Non-Technical Skills for Surgeons ( NOTSS ) scoring . RESULTS Twenty trainees were evenly r and omised to either PTr or FTr . No differences in performance were seen except for the total time the embolic protection device ( EPD ) was deployed ( 9.4 min for the PT vs. 8.1 min for the FT , p = 0.02 ) . Total time ( 26.3 vs. 25.5 min , p = 0.94 ) , fluoroscopy time ( 15.8 vs. 14.4 min , p = 0.68 ) , number of roadmaps ( 10.5 vs. 11.0 , p = 0.54 ) , amount of contrast ( 53.5 vs. 58.0 ml , p = 0.33 ) , time to deploy the EPD ( 0.9 vs. 0.8 min , p = 0.31 ) and time to catheterise the CCA ( 9.2 vs. 8.9 min , p = 0.94 ) were similar . Qualitative performances as measured by expert ratings ( score 24 vs. 24 , p = 0.49 ) and NOTSS ( p > 0.05 for all categories ) were also comparable . CONCLUSIONS Part- and full-task rehearsals are equally effective with respect to the operative performance of a simulated CAS intervention . This finding makes a patient-specific rehearsal more efficient and may increase the feasibility of implementation of this technology into medical practice Objectives : The development of a structured virtual reality ( VR ) training curriculum for colonoscopy using high-fidelity simulation . Background : Colonoscopy requires detailed knowledge and technical skill . Changes to working practice s in recent times have reduced the availability of traditional training opportunities . Much might , therefore , be achieved by applying novel technologies such as VR simulation to colonoscopy . Scientifically developed device-specific curricula aim to maximize the yield of laboratory-based training by focusing on vali date d modules and linking progression to the attainment of benchmarked proficiency criteria . Methods : Fifty participants comprised of 30 novices ( < 10 colonoscopies ) , 10 intermediates ( 100 to 500 colonoscopies ) , and 10 experienced ( > 500 colonoscopies ) colonoscopists were recruited to participate . Surrogates of proficiency , such as number of procedures undertaken , determined prospect i ve allocation to 1 of 3 groups ( novice , intermediate , and experienced ) . Construct validity and learning value ( comparison between groups and within groups respectively ) for each task and metric on the chosen simulator model determined suitability for inclusion in the curriculum . Results : Eight tasks in possession of construct validity and significant learning curves were included in the curriculum : 3 abstract tasks , 4 part-procedural tasks , and 1 procedural task . The whole-procedure task was valid for 11 metrics including the following : “ time taken to complete the task ” ( 1238 , 343 , and 293 s ; P < 0.001 ) and “ insertion length with embedded tip ” ( 23.8 , 3.6 , and 4.9 cm ; P = 0.005 ) . Learning curves consistently plateaued at or beyond the ninth attempt . Valid metrics were used to define benchmarks , derived from the performance of the experienced cohort , for each included task . Conclusions : A comprehensive , stratified , benchmarked , whole-procedure curriculum has been developed for a modern high-fidelity VR colonoscopy simulator PURPOSE : The aim of this study was to compare skills sets during a h and -assisted and straight laparoscopic colectomy on an augmented reality simulator . METHODS : Twenty-nine surgeons , assigned r and omly in 2 groups , performed laparoscopic sigmoid colectomies on a simulator : group A ( n = 15 ) performed h and -assisted then straight procedures ; group B ( n = 14 ) performed straight then h and -assisted procedures . Groups were compared according to prior laparoscopic colorectal experience , performance ( time , instrument path length , and instrument velocity changes ) , technical skills , and operative error . RESULTS : Prior laparoscopic colorectal experience was similar in both groups . Both groups had better performances with the h and -assisted approach , although technical skill scores were similar between approaches . The error rate was higher with the h and -assisted approach in group A , but similar between both approaches in group B. CONCLUSIONS : These data define the metrics of performance for h and -assisted and straight laparoscopic colectomy on an augmented reality simulator . The improved scores with the h and -assisted approach suggest that with this simulator a h and -assisted model may be technically easier to perform , although it is associated with increased intraoperative errors Background Minimally invasive surgery in small children and infants requires special skills and training . This experimental study compares the efficiency of an in vitro pelvic trainer ( PT ) and an a in vivo animal model ( AM ) . Methods For this study , 12 residents were prospect ively r and omized into two groups . Initially , all had to pass a basic skill assessment ( 3 tasks ) . Then endoscopic small bowel biopsy was performed ( 8 times ) either with the in vitro PT ( group A ) or the in vivo AM ( group B ) . Finally , all had to demonstrate this procedure in the in vivo AM and repeat the basic skill assessment . A quality index ( complications , suture , biopsy ) was evaluated . Results Initially , there was no difference between the two groups . Interestingly , the mean regression gradient of the index for the in vitro PT ( group A ) was significantly better than for the in vivo AM ( group B ) . In the final in vivo operation , however , the mean index for the in vitro PT ( group A ) worsened significantly , whereas it increased for the in vivo AM ( group B ) ( p = 0.037 ) . Conclusion Adequate training for an isolated mechanical task such as gut biopsy can be supplied using a pelvic trainer or animal model with similar effects . However in vivo performance of the same task requires secondary surgical skills , which are conveyed during live training with greater success . Consequently , stepwise teaching with both modules seems reasonable before these procedures are approached in neonates or small children Background We hypothesized that simulator-generated metrics and intraoperative errors may be able to differentiate the technical differences between h and -assisted laparoscopic ( HAL ) and straight laparoscopic ( SL ) approaches . Methods Thirty-eight trainees performed two laparoscopic sigmoid colectomies on an augmented reality simulator , r and omly starting by a SL ( n = 19 ) or HAL ( n = 19 ) approach . Both approaches were compared according to simulator-generated metrics , and intraoperative errors were collected by faculty . Results Sixty-four percent of surgeons were experienced ( > 50 procedures ) with open colon surgery . Fifty-five percent and 69 % of surgeons were inexperienced ( < 10 procedures ) with SL and HAL colon surgery , respectively . Time ( P < 0.001 ) , path length ( P < 0.001 ) , and smoothness ( P < 0.001 ) were lower with the HAL approach . Operative times for sigmoid and splenic flexure mobilization and for the colorectal anastomosis were significantly shorter with the HAL approach . Time to control the vascular pedicle was similar between both approaches . Error rates were similar between both approaches . Operative time , path length , and smoothness correlated directly with the error rate for the HAL approach . In contrast , error rate inversely correlated with the operative time for the SL approach . Conclusions A HAL approach for sigmoid colectomy accelerated colonic mobilization and anastomosis . The difference in correlation between both laparoscopic approaches and error rates suggests the need for different skills to perform the HAL and the SL sigmoid colectomy . These findings may explain the preference of some surgeons for a HAL approach early in the learning of laparoscopic colorectal surgery OBJECTIVE The aim of this study was to compare a simulator with the human cadaver model for h and -assisted laparoscopic colorectal skills acquisition training . DESIGN An observational prospect i ve comparative study was conducted to compare the laparoscopic surgery training models . SETTING The study took place during the laparoscopic colectomy training course performed at the annual scientific meeting of the American Society of Colon and Rectal Surgeons . PARTICIPANTS Thirty four practicing surgeons performed h and -assisted laparoscopic sigmoid colectomy on human cadavers ( n = 7 ) and on an augmented reality simulator ( n = 27 ) . Prior laparoscopic colorectal experience was assessed . Trainers and trainees completed independently objective structured assessment forms . Training models were compared by trainees ' technical skills scores , events scores , and satisfaction . RESULTS Prior laparoscopic experience was similar in both surgeon groups . Generic and specific skills scores were similar on both training models . Generic events scores were significantly better on the cadaver model . The 2 most frequent generic events occurring on the simulator were poor h and -eye coordination and inefficient use of retraction . Specific events were scored better on the simulator and reached the significance limit ( p = 0.051 ) for trainers . The specific events occurring on the cadaver were intestinal perforation and left ureter identification difficulties . Overall satisfaction was better for the cadaver than for the simulator model ( p = 0.009 ) . CONCLUSIONS With regard to skills scores , the augmented reality simulator had adequate qualities for the h and -assisted laparoscopic colectomy training . Nevertheless , events scores highlighted weaknesses of the anatomical replication on the simulator . Although improvements likely will be required to incorporate the simulator more routinely into the colorectal training , it may be useful in its current form for more junior trainees or those early on their learning curve Objective To demonstrate that virtual reality ( VR ) training transfers technical skills to the operating room ( OR ) environment . Summary Background Data The use of VR surgical simulation to train skills and reduce error risk in the OR has never been demonstrated in a prospect i ve , r and omized , blinded study . Methods Sixteen surgical residents ( PGY 1–4 ) had baseline psychomotor abilities assessed , then were r and omized to either VR training ( MIST VR simulator diathermy task ) until expert criterion levels established by experienced laparoscopists were achieved ( n = 8) , or control non-VR-trained ( n = 8) . All subjects performed laparoscopic cholecystectomy with an attending surgeon blinded to training status . Videotapes of gallbladder dissection were review ed independently by two investigators blinded to subject identity and training , and scored for eight predefined errors for each procedure minute ( interrater reliability of error assessment r > 0.80 ) . Results No differences in baseline assessment s were found between groups . Gallbladder dissection was 29 % faster for VR-trained residents . Non-VR-trained residents were nine times more likely to transiently fail to make progress ( P < .007 , Mann-Whitney test ) and five times more likely to injure the gallbladder or burn nontarget tissue ( chi-square = 4.27 , P < .04 ) . Mean errors were six times less likely to occur in the VR-trained group ( 1.19 vs. 7.38 errors per case;P < .008 , Mann-Whitney test ) . Conclusions The use of VR surgical simulation to reach specific target criteria significantly improved the OR performance of residents during laparoscopic cholecystectomy . This validation of transfer of training skills from VR to OR sets the stage for more sophisticated uses of VR in assessment , training , error reduction , and certification of surgeons The aim of this study was to assess skill retention in the operating room following completion of a proficiency-based laparoscopic skills curriculum . Novices ( n = 15 ) were r and omized to a control and a training group that practice d to proficiency on the Fundamentals of Laparoscopic Surgery suturing model . The performance of both groups was assessed on the simulator and on a live porcine laparoscopic Nissen fundoplication model at training completion ( posttest ) and 5 months later ( retention test ) . Training to proficiency required 4.7 ±1.2 hours and 41 ± 10 repetitions . Trained participants outperformed controls , and their performance deteriorated slightly between posttests and retention tests on the simulator ( 505 ± 22 vs 462 ± 50 , respectively ; P < .05 ) but not in operating room ( 263 ± 138 vs 279 ± 88 , respectively ; P = .38 ) . Proficiency-based simulator training results in durable improvement in operative skill of trainees even in the absence of practice for up to 5 months . Minute simulator performance changes do not translate to the operating room OBJECTIVES The purpose of the present study was to evaluate the quality of preservation ( tissue plane , named vessels identification , consistency of colon and rectum ) , quality of performing procedures , difficulties and problems and finally the satisfaction of surgeons in laparoscopic proctocolectomy in soft cadaver . SETTING Colorectal Division , Department of Surgery and Surgical Training Center Department of Anatomy , Faculty of Medicine , Chulalongkorn University . DESIGN Prospect i ve descriptive study MATERIAL AND METHOD 10 soft cadavers were scheduled for laparoscopic proctocolectomy . The procedures ( colon-rectum mobilization and named vessels identification ) were performed by 14 experienced surgeons ( 8 colorectal surgeons ) and assisted by surgical residents . The quality of preservation , successfulness and the satisfaction in performing the procedures were recorded using question naires for evaluation . RESULTS The preservation was very good in every aspect especially tissue plane between colon , mesocolon and retroperitoneum which was clearly dissected , same asfasciapropria of rectum . The named vessels and the tissue consistency were very well preserved and tolerated to laparoscopic equipment h and ling . The surgeons were satisfied with the tissue h and ling and dissections . There were two difficulties , the first was air leakage but simply corrected with purse string suture and the second was unflavored smell which was not concerned . Laparoscopic proctocolectomy could be completely performed in soft cadaver . CONCLUSION Laparoscopic proctocolectomy could be performed in soft cadavers with great satisfaction . Repeated practice is possible , so the surgeons can gain their experiences outside the operating theatre . This success may shorten the learning curve and may be the new era in cadaver-based training Traditionally military aviators have prepared for air-to-ground bombing missions with maps and aerial photographs of their targets . Mission rehearsal systems augment these media by allowing pilots to view simulated ingress to their target , as seen from the cockpit perspective . In the present experiment we assessed the benefits of mission rehearsal with a task requiring observers to view recorded approaches to target objects and to detect the target objects as quickly as possible . Results indicated that premission simulations allowed observers to detect target objects at greater st and -off ranges than did study with maps and aerial photographs alone . Actual or potential applications of this research include the deployment of a mission rehearsal system to assist aviators ' mission planning OBJECTIVE The objective of this study was to determine whether a learning curve for laparoscopic fundoplication can be defined , and whether steps can be taken to avoid any difficulties associated with it . SUMMARY BACKGROUND DATA Although early outcomes after laparoscopic fundoplication have been promising , complications unique to the procedure have been described . Learning curve problems may contribute to these difficulties . Although training recommendations have been published by some professional bodies , there is disagreement about what constitutes adequate supervised experience before the solo performance of laparoscopic antireflux surgery , and the true length of the learning curve . METHODS The outcome of 280 laparoscopic fundoplications undertaken by 11 surgeons during a 46-month period was assessed prospect ively . The experience was analyzed in three different ways : 1 ) by an assessment of the overall learning experience within chronologically arranged groups , 2 ) by an assessment of all individual experiences grouped according to the experience of individual surgeons , and 3 ) by a comparison of early outcomes of operations performed by the surgeons who initiated laparoscopic fundoplication with the early experience of surgeons beginning laparoscopic fundoplication later in the overall institutional experience . RESULTS The complication , reoperation , and laparoscopic to open conversion rates all were higher in the first 50 cases performed by the overall group , and in the first 20 cases performed by each individual surgeon . These rates were even higher in the initial first 20 cases , and the first 5 individual cases . However , adverse outcomes were less likely when surgeons began fundoplication later in the overall experience , when experienced supervision could be provided . CONCLUSIONS A learning curve for laparoscopic fundoplication can be defined . Experienced supervision should be sought by surgeons beginning laparoscopic fundoplication during their first 20 procedures . This should minimize adverse outcomes associated with an individual 's learning curve BACKGROUND The purpose of this study was to develop a performance-based laparoscopic suturing curriculum using simulators and to test the effectiveness ( transferability ) of the curriculum . STUDY DESIGN Surgical residents ( PGY1 to PGY5 , n = 17 ) proficient in basic skills , but with minimal laparoscopic suturing experience , were enrolled in an IRB-approved , r and omized controlled protocol . Subjects viewed an instructional video and were pretested on a live porcine laparoscopic Nissen fundoplication model by placing three gastrogastric sutures tied in an intracorporeal fashion . A blinded rater objective ly scored each knot based on a previously published formula ( 600 minus completion time [ sec ] minus penalties for accuracy and knot integrity errors ) . Subjects were stratified according to pretest scores and r and omized . The trained group practice d on a videotrainer suturing model until an expert-derived proficiency score ( 512 ) was achieved on 12 attempts . The control group received no training . Both the trained and control groups were posttested on the porcine Nissen model . RESULTS For the training group , mean time to demonstrate simulator proficiency was 151 minutes ( range 107 to 224 minutes ) and mean number of attempts was 37 ( range 24 to 51 attempts ) . Both the trained and control groups demonstrated significant improvement in overall score from baseline . But the trained group performed significantly better than the control group at posttesting ( 389 + /- 70 versus 217 + /- 140 , p < 0.001 ) , confirming curriculum effectiveness . CONCLUSIONS These data suggest that training to a predetermined expert level on a videotrainer suture model provides trainees with skills that translate into improved operative performance . Such curricula should be further developed and implemented as a means of ensuring proficiency BACKGROUND Proficiency-based simulator training in laparoscopic suturing leads to improved operative performance , but the skill transfer is incomplete . The objective of this study was to examine the stress level of trainees during the transition from the simulator to the operating room ( OR ) and its impact on performance . METHODS Novices ( n = 20 ) were r and omized into training and control groups . After the training group achieved proficiency in laparoscopic suturing , both groups were tested on a live porcine , laparoscopic Nissen fundoplication model . Participant performance was assessed using an objective score . Stress level was evaluated by recording beat-to-beat heart rate ( BBHR ) and short-term heart rate variability ( STHRV ) at baseline , after achieving proficiency ( only the training group ) and in the OR . Repeated measurement analysis of variance ( ANOVA ) and t test were used for analysis . RESULTS Baseline simulator performance and data for heart rate variability were similar for both groups . After achieving simulator proficiency , the trained group demonstrated the anticipated decrease in performance ( mean average + or - SEM ) in the OR ( 524 + or - 17 vs 290 + or - 95 ; P < .001 ) , and an increase in BBHR ( 98 + or - 14 vs115 + or - 18 ; P < .001 ) but not STHRV ( 4.1 + or - 0.8 vs 3.7 + or - 0.9 ; P = .5 ) . A similar but lesser increase of the BBHR was observed in the control group compared to the study group . CONCLUSION BBHR was a more sensitive measure of stress level compared with STHRV . The increased BBHR observed in the OR that reflects stress and performance anxiety may explain the incomplete transfer of simulator-acquired skill in novice learners OBJECTIVES The purpose of this study was to evaluate the surgical anatomy , tissue plane , organ consistency of soft cadaver and the possibility of minimally invasive surgery training in soft cadaver . SETTING Surgical Training Center . Department of Anatomy and Department of Surgery Faculty of Medicine , Chulalongkorn University . DESIGN Prospect i ve descriptive study . MATERIAL AND METHOD 2 soft cadavers were scheduled for fully laparoscopic surgery in upper gastrointestinal , colorectal , hepatopancreatobiliary and solid organs surgery . All the procedures were performed by the experienced surgical staffs and assisted by surgical staffs and /or surgical residents . The surgical anatomy , tissue plane , organ consistency and the satisfactory in performing the procedures were recorded for evaluation . RESULTS The surgical anatomy , the tissue consistency the anatomical plane were very well preserved with mean score of 4.72 + /- 0.45 . All the surgeons were satisfied with the findings , the mean score was 4.97 + /- 0.18 . All the plan procedures were completely performed with great satisfactory results . CONCLUSION The Minimally Invasive Surgery Training in Soft Cadaver ( MIST-SC ) was feasible with great satisfactory . This successful integration of basic and advanced laparoscopic procedures into the soft cadaver setting would be the next step in evolution of MIS training Implementing laparoscopic surgery is a challenge that should prompt educational research in an attempt to establish a link between instruction and the quality of patient care . This r and omized study was undertaken to compare the impact of instruction versus passive observation on laparoscopic skills . The task was stitching and tying a surgeon 's knot on a perforated ulcer in a foam stomach placed in a simulator . Outcome measures were accuracy error , goal -directed and non– goal -directed actions , operating time , and tissue damage . Time/motion analysis was carried out by an masked assessor . Twelve participants were well matched for h and –eye coordination at pretesting . Regardless of whether instruction was given or not , a positive correlation was found between overall actions and operating time , non– goal -directed actions and operating time , and overall actions and non– goal directed actions . Intraoperative instruction decreased errors , but this study did not have sufficient power to detect small differences in other outcome measures . The teaching of minimal-access surgery should increasingly be based on educational research data rather than on unstructured rating by attending surgeons |
1,643 | 21,435,786 | Suboptimal dosing of TENS and inappropriate outcome assessment were particularly prevalent weaknesses indicating low fidelity .
Poor implementation fidelity was identified as a significant source of bias in systematic review s of TENS studies and might explain lack of consistent treatment effects of TENS in pain . | The benefits of transcutaneous electrical nerve stimulation ( TENS ) for pain relief have not been reliably established , as most systematic review s find poor method ological quality in many studies .
The paradox within the evidence base for TENS is that despite identified sources of bias that may lead to an overestimation of treatment effects , no benefits for TENS can be clearly demonstrated .
Our hypothesis was that low fidelity in studies ( bias leading to an underestimation of treatment effects ) may account for inconclusive findings . | & NA ; The placebo effect of transcutaneous electrical stimulation was studied in 93 patients in a double‐blind cross‐over trial using a genuine stimulator and a placebo machine . Placebo analgesic effects occurred in 32 % of trials , as compared with 48 % for actual stimulation . The placebo effect of the transcutaneous electrical stimulator is similar to the placebo effect that is noted in other double‐blind studies in which medicationms are used The aim of this study was to test the efficacy of shortterm transcutaneous electrical nerve stimulation ( TENS ) treatment in chronic pain with respect to pain intensity and patients ’ satisfaction with treatment results . We therefore performed a r and omised controlled trial comparing TENS and sham TENS . Patients , research ers and therapists were blinded for treatment allocation . One hundred and sixty-three patients with chronic pain referred to the Pain Centre entered the study . Conventional TENS and sham TENS were applied in the segments of pain , for a period of ten days . Outcome measures were pain intensity ( visual analogue scale ) and patients ’ satisfaction with treatment result ( yes or no ) . The proportions of patients satisfied with treatment result differed significantly for TENS compared to sham TENS ( 58 and 42.7 % respectively , x2=3.8 , p=0.05 ) . However , no differences in pain intensity were found for patients treated with TENS or sham TENS . Only for patients satisfied with treatment results pain intensity gradually decrease equally both for TENS and sham TENS with repeated treatment application OBJECTIVE Few non-surgical conditions are more painful than rib fractures . There are a few methods for pain relief in patients with minor rib fractures . METHODS We used a non-steroidal anti-inflammatory drug ( NSAID , Naproxen sodium ) and transcutaneous electrical nerve stimulator ( TENS ) to control pain of the patients with uncomplicated minor rib fractures . One hundred consecutive patients admitted to Kartal Education and Research Hospital Emergency Service , were r and omized into four groups . The patients were assigned to one of the following pain treatments : NSAID , TENS , NSAID plus inactive TENS or placebo . The patients used NSAIDs and placebo four times a day and TENS twice a day for 3 days . All patients were asked to assess their pain level with a scoring system on days 0 , 1 and 3 . RESULTS The most effective treatment was TENS on days 1 and 3 ( P<0.05 ) . Although NSAID and NSAID plus inactive TENS controlled pain better than placebo on day 1 ( P<0.05 ) , this superiority did not continue to day 3 ( P>0.05 ) . There was no difference between NSAID and NSAID plus inactive TENS in controlling pain on either days 1 or 3 . CONCLUSION We conclude that TENS was more effective than NSAID or placebo in patients with uncomplicated minor rib fractures , because of its prominent and admirable efficacy in reduction of pain Venipuncture continues to be considered a painful and unpleasant experience for those receiving medical treatment . A prospect i ve study investigating whether the application of a transcutaneous electrical nerve stimulator ( TENS ) decreases the complaints of pain and unpleasantness with i.v . needle insertion was conducted using a group of 71 subjects who were double-blinded and r and omized to one of three groups : TENS , placebo-TENS , and control . This article gives an overview of this research and describes its findings Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field OBJECTIVE This study examined the optimal stimulation duration of transcutaneous electrical nerve stimulation ( TENS ) for relieving osteoarthritic knee pain and the duration ( as measured by half-life ) of post-stimulation analgesia . SUBJECTS Thirty-eight patients received either : ( i ) 20 minutes ( TENS20 ) ; ( ii ) 40 minutes ( TENS40 ) ; ( iii ) 60 minutes ( TENS60 ) of TENS ; or ( iv ) 60 minutes of placebo TENS ( TENS(PL ) ) 5 days a week for 2 weeks . METHODS A visual analogue scale recorded the magnitude and pain relief period for up to 10 hours after stimulation . RESULTS By Day10 , a significantly greater cumulative reduction in the visual analogue scale scores was found in the TENS40 ( 83.40 % ) and TENS60 ( 68.37 % ) groups than in the TENS20 ( 54.59 % ) and TENS(PL ) ( 6.14 % ) groups ( p < 0.000 ) , such a group difference was maintained in the 2-week follow-up session ( p < 0.000 ) . In terms of the duration of post-stimulation analgesia period , the duration for the TENS40 ( 256 minutes ) and TENS60 ( 258 minutes ) groups was more prolonged than in the other 2 groups ( TENS20 = 168 minutes , TENS(PL ) = 35 minutes ) by Day10 ( p < 0.000 ) . However , the TENS40 group produced the longest pain relief period by the follow-up session . CONCLUSION 40 minutes is the optimal treatment duration of TENS , in terms of both the magnitude ( VAS scores ) of pain reduction and the duration of post-stimulation analgesia for knee osetoarthritis Thirty patients with chronic pain due to osteoarthrosis ( OA ) of the knee were enrolled in a r and omised double-blind cross-over trial of self-administered transcutaneous electrical nerve stimulation ( TENS ) and placebo TENS . Medication was st and ardised to paracetamol tablets only . As measured on visual analogue scales for pain relief 46 % of patients responded to active therapy and 43 % to placebo . The length of pain relief during active therapy was significantly longer than that during placebo . At the end of the trial more patients wanted to continue using active TENS in preference to placebo or their original medication . Although most of the parameters observed favoured active TENS , it was not possible to establish its clear superiority over placebo , because the response rate to placebo TENS was high and sustained for at least 3 weeks . This trial suggests that a longer study is required to establish the role of TENS as a therapeutic agent in the treatment of the pain of chronic arthritis Objective To assess the value of transcutaneous electrical nerve stimulation ( TENS ) during cervical laser therapy BACKGROUND AND PURPOSE It is not fully understood how transcutaneous electrical nerve stimulation ( TENS ) intensity affects mechanical pain threshold . METHOD Sixty-six healthy volunteers ( 13 male , 53 female ; 132 h and s ) without prior experience of TENS participated in the study , which comprised a r and omized single-blind controlled trial . TENS was administered for 20 minutes through electrodes ( 25 x 25 mm ) placed on the h and s and forearms with a fixed frequency of 100 Hz and pulse duration of 150 micros . TENS intensity was r and omized and allocated in a concealed manner so that one arm received TENS with stimulation intensity set at participants ' subjective sensory threshold and the other received TENS with stimulation intensity continuously adjusted by physiotherapists to a strong but comfortable non-painful stimulation . Observers were blinded to stimulation intensity levels . RESULTS Mechanical pain threshold increased significantly , by a mean total of 0.79 kg/cm2 ( 95 % confidence interval [ 95 % CI ] : 0.54 - 1.04 ) ( p < 0.001 ) on the strong but comfortable non-painful stimulation side . The mean change in mechanical pain threshold on the sensory threshold side was 0.19 kg/cm2 and did not reach statistical significance ( 95 % CI-0.15 to 0.51 ) . The mean stimulation intensity level for sensory threshold was 6.7 mA ( 95 % CI : 5.65 to 7.83 ) which was significantly lower ( p < 0.001 ) than the mean stimulation intensity for the strong stimulation , which was 20.5 mA ( 95 % CI 16.6 to 24.4 ) , respectively . The strong stimulation levels were , on average , 3.05 times higher than sensory threshold , but individual variations were large ( range 1.2 - 6.1 ) . CONCLUSIONS TENS administered at a strong but comfortable non-painful stimulation intensity increases mechanical pain threshold ipsi-laterally in healthy subjects , whereas TENS administered at sensory threshold intensity does not . TENS may be ineffective if electrodes are placed contralaterally or distant to the pain site and if stimulation intensity levels are not titrated to subjective strong levels . Further clinical trials are needed to clarify if these findings may also be generalized to population s of chronic pain sufferers A double-blind controlled analgesic study was undertaken in out patients suffering acute traumatic pain . One hundred patients completed the study and were r and omly assigned to four treatment groups , each receiving either functioning transcutaneous electrical nerve stimulators ( TENS ) , placebo TENS , acetaminophen with codeine and a functioning TENS , or acetaminophen with codeine and a placebo TENS . Pain was assessed prior to treatment , at 48 hours , and at one month using a visual analog scale . A statistically significant difference in pain relief occurred between the placebo and functioning TENS groups . The TENS was approximately as effective as acetaminophen ( 300 - 600 mg ) with codeine ( 30 - 60 mg ) but had no side effects . Transcutaneous electrical nerve stimulators have been shown to be effective in the management of acute traumatic pain and may be indicated for patients who can not be given medications & NA ; This study evaluated the effects of varying frequency , intensity and stimulation site , of transcutaneous electrical nerve stimulation ( TENS ) in an experimental model of pain . In a double‐blind design 240 volunteers were r and omised to one of six experimental TENS groups , a sham TENS or control ( n=30 per group ; gender balanced ) . Two TENS frequencies ( 110 or 4 Hz ) and two intensities ( strong but comfortable or highest tolerable ) at a fixed pulse duration ( 200 & mgr;s ) were applied at three sites relative to the measurement site ( segmentally , extrasegmentally or a combination of these ) , for 30 min . Pressure pain thresholds ( PPT ) were measured using a pressure algometer , in the first dorsal interosseous muscle , every 10 min , during stimulation and for a further 30 min . The high frequency , high intensity segmental , and combined stimulation groups , showed rapid onset and significant hypoalgesic effects . This effect was sustained for 20 min post‐stimulation in the high frequency segmental group . All other TENS intervention groups showed hypoalgesic responses similar to the sham TENS group , and none of these groups reached a clinical ly significant hypoalgesic level . Conclusions : The role of TENS frequency , intensity and site are pivotal to achieving optimal hypoalgesic effects , during and after stimulation . Clinical applications of these parameter combinations require further investigations Chronic pain associated with breast cancer treatment is becoming increasingly recognized . Patients with this condition can experience significant physical and psychological morbidity and may benefit from nonpharmacological interventions as part of a multidisciplinary team approach . We compared the effectiveness of transcutaneous electrical nerve stimulation ( TENS ) , transcutaneous spinal electroanalgesia ( TSE ) , and a placebo ( sham TSE ) in a r and omized controlled trial . The study sample comprised 41 women with chronic pain following breast cancer treatment , and outcome measures included pain report , pain relief , pain interference , anxiety and depression , arm mobility , and analgesic consumption . There was little evidence to suggest that TENS or TSE were more effective than placebo . All three interventions had beneficial effects on both pain report and quality of life , a finding that may be due to either psychophysical improvements result ing from the personal interaction involved in the treatment or a placebo response . Although electrical stimulation appears to be well tolerated in this population , further research is needed to establish its effectiveness for chronic cancer treatment-related pain Thirty-six non-hospitalized subjects with chronic pain from OA of the knee participated in an evaluation of transcutaneous electrical nerve stimulation ( TENS ) and naproxen , an NSAID . All pre-experiment treatment was withdrawn . Each subject experienced in some order three 3-week treatment phases : NSAID plus placebo TENS ; TENS plus placebo drug ; and double placebo . A broad range of pain measures was used , including daily diary ratings , and four-times-per-day ratings entered into a small electronic data logger ( the PIPER ) worn by the subject . A substantial placebo response occurred across all conditions , which may have masked treatment differences . Broad comparisons across subjects , combining the four main measures of pain , found no significant differences among the three experimental treatments . Analysis of diary and PIPER data for individuals suggested that , in a small minority of subjects , the NSAID plus placebo TENS combination may be more effective than double placebo . The PIPER ratings seemed to tap aspects of the pain experience different from those captured by conventional measures , suggesting the value of very frequent pain assessment s , such as those entered by a subject into the PIPER , in the study of chronic pain & NA ; Transcutaneous electrical nerve stimulation ( TENS ) is a frequently applied therapy in chronic pain although evidence for effectiveness is inconclusive . Several types of TENS , based on different combinations of frequency , pulse duration and intensity , exist . The precise mechanism of action and the relevance of combinations of stimulus parameters are still unclear . To compare the effectiveness of three types of TENS we conducted a r and omized , single blinded crossover trial . Patients received two times a 2‐week period of daily TENS treatment , separated by a washout period of 2 weeks . In total , 180 chronic pain patients were r and omized into three groups . In group 1 , high frequency , low intensity TENS ( HFT ) was compared with high frequency , high intensity TENS ( HIT ) . In groups 2 and 3 , HFT and HIT were compared with a control TENS ( COT ) . The order of applying the different modalities of TENS in each group was also r and omized . Primary outcome was the patient 's overall assessment of effectiveness and pain reduction ( VAS ) . No differences were found in patient 's assessment or pain reducing effect between the three groups , indicating no superiority of one type of TENS . In total , 56 % continued TENS after the 2‐week treatment period . At 6 months , 42 % of all patients still used TENS . We concluded that there were no differences in effectiveness for the three types of TENS used in this study . Because no placebo group was included , no definite conclusions on effectiveness of TENS in general in the treatment of chronic pain could be made OBJECTIVE To evaluate the efficacy of transcutaneous electrotherapy for chronic painful peripheral neuropathy in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Thirty-one patients with symptoms and signs of peripheral neuropathy were r and omized to the electrotherapy or sham treatment ( control ) group . The electrostimulation was given by a portable unit ( H-Wave machine ) than generated a biphasic , exponentially decaying waveform ( pulse width 4 ms , 25–35 V , ≥ 2 Hz ) . Patients treated each of their lower extremities for 30 min daily for 4 weeks at home . Nine patients from the sham-treatment group participated for a second period , during which all of them received the active electrotherapy . Patient 's degree of pain and discomfort was grade d on a scale of 0 to 5 . RESULTS In the sham-treated group ( n = 13 ) , the neuropathic symptoms improved in five ( 38 % ) patients , and the pain score declined from 2.92 ± 0.13 to 2.38 ± 0.26 ( P < 0.04 ) , suggesting a procedure-related placebo effect . In the electrotherapy group ( n = 18 ) , symptomatic improvement was seen in 15 ( 83 % ) cases , 3 of which were completely asymptomatic ; the pain score declined from 3.17 ± 0.12 to 1.44 ± 0.25 ( P < 0.01 ) and the posttreatment pain scores were considerably lower ( P < 0.03 ) , indicating a substantial treatment effect over and above any placebo influence . Patients in the electrotherapy group reported greater reduction in symptoms ( 52 ± 7 % vs. 27 ± 10 % in control subjects , P < 0.05 ) on an analog scale . Moreover , the electrotherapy decreased pain scores ( from 3.0 ± 0.62 to 1.56 ± 0.32 , P < 0.02 ) in nine patients who had received sham treatment earlier . CONCLUSIONS A form of transcutaneous electrotherapy ameliorated the pain and discomfort associated with peripheral neuropathy . This novel modality offers a potential non-pharmacological treatment option UNLABELLED This multicenter study assessed the feasibility of conducting a phase III trial of transcutaneous electrical nerve stimulation ( TENS ) in patients with cancer bone pain recruited from palliative care services . Eligible patients received active and placebo TENS for 1 hour at site of pain in a r and omized crossover design ; median interval between applications 3 days . Responses assessed at 30 and 60 minutes included numerical and verbal ratings of pain at rest and on movement , and pain relief . Recruitment , tolerability , adverse events , and effectiveness of blinding were also evaluated . Twenty-four patients were r and omised and 19 completed both applications . The intervention was well tolerated . Five patients withdrew : 3 due to deteriorating performance status , and 2 due to increased pain ( 1 each following active and placebo TENS ) . Confidence interval estimation around the differences in outcomes between active and placebo TENS suggests that TENS has the potential to decrease pain on movement more than pain on rest . Nine patients did not consider that a placebo was used ; the remaining 10 correctly identified placebo TENS . Feasibility studies are important in palliative care prior to undertaking clinical trials . Our findings suggest that further work is required on recruitment strategies and refining the control arm before evaluating TENS in cancer bone pain . PERSPECTIVE Cancer bone pain is common and severe , and partly mediated by hyperexcitability . Animal studies suggest that Transcutaneous Electrical Nerve Stimulation can reduce hyperalgesia . This study examined the feasibility of evaluating TENS in patients with cancer bone pain in order to optimize methods before a phase III trial Objective : To investigate the hypoalgesic effects of transcutaneous electrical nerve stimulation ( TENS ) upon low back pain ( LBP ) in people with multiple sclerosis ( MS ) . Design : A r and omized double-blind placebo controlled clinical pilot study . Subjects and setting : Fifteen people with MS were recruited and r and omly allocated to one of the following groups under double blind conditions ( n = 5 per group ) : TENS 1 ( 4 Hz , 200 µs ) , TENS 2 ( 110 Hz , 200 µs ) , placebo TENS . Interventions : Treatment was applied for 45 minutes three times a week for six weeks with a four-week follow-up . Outcome measures : The following outcome measures were taken at weeks 1 , 6 , and 10 : visual analogue scale ( VAS ) ( for current LBP , right leg pain , left leg pain ) ; Leeds Multiple Sclerosis Quality of Life Question naire ; Rol and Morris Disability Question naire ; Short Form-36 ( SF-36 ) Version 1 ; and the McGill Pain Question naire ( MPQ ) . VAS for current LBP , right and left leg pain were also taken before and after treatment , and once a week during the follow-up period . Results : Analysis showed no statistically significant effects for any of the data . However , both active treatment groups showed a trend of improvement in the majority of the outcome measures . Conclusion : Active TENS was more effective than placebo TENS in decreasing VAS scores following each treatment although results were not statistically significant . Further work in this area is warranted and should include a larger number of participants in the form of a r and omized controlled clinical trial to determine the efficacy of this modality OBJECTIVES A preliminary examination of NMES and combined NMES/TENS for the management of chronic back pain . DESIGN Double-blind , placebo-controlled , r and omized repeated measures . SUBJECTS AND SETTING Consecutive sample of 24 chronic back pain patients ( 16 women and 8 men ) attending an outpatient pain clinic ( mean age 51.67 years , mean pain duration 3.83 years ) . All treatments were administered at home . INTERVENTIONS Subjects self-administered NMES , combined NMES/TENS , TENS , and placebo treatments . Each treatment had a duration of 5 consecutive hours per day over 2 consecutive days , with a 2-day hiatus between treatments to minimize carryover effects . MAIN OUTCOME MEASURES Pain reduction was assessed through pretreatment to posttreatment differences on the Present Pain Intensity ( PPI ) scale , and a visual analogue scale of Pain Intensity ( VAS-I ) . Posttreatment pain relief was assessed using a visual analogue scale of Pain Relief ( VAS-R ) . RESULTS Combined treatment , NMES , and TENS each produced significant pretreatment to posttreatment reductions in pain intensity as measured by both the PPI and VAS-I ( p < .05 ) . Combined treatment was superior to placebo on pain reduction ( p = .001 , p = .016 ) as well as pain relief ( p < .001 ) . Combined treatment was also superior to both TENS and NMES for pain reduction and pain relief ( p < .01 ) . NMES and TENS were superior only to placebo for pain relief ( p < .001 ) . CONCLUSIONS Combined NMES/TENS treatment consistently produced greater pain reduction and pain relief than placebo , TENS , or NMES . NMES alone , although less effective , did produce as much pain relief as TENS . Although preliminary , this pattern of results suggests that combined NMES/TENS may be a valuable adjunct in the management of chronic back pain . Further research investigating the effectiveness of both NMES and combined NMES/TENS seems warranted OBJECTIVE To determine whether alternating frequency transcutaneous electric nerve stimulation ( TENS ) at 2 and 100Hz ( 2/100Hz ) has a more potent hypoalgesic effect than a fixed frequency at 2 or 100Hz in healthy participants . DESIGN A single-blind r and omized controlled trial with a convenience sample . SETTING University physiotherapy department . PARTICIPANTS Sixty-four healthy volunteers ( 32 men [ mean age , 28.1+/-5.9y ] , 32 women [ mean age , 27.7+/-5.6y ] ) were recruited and r and omly divided into 4 groups . INTERVENTIONS The 4 groups received TENS delivered at ( 1 ) 2Hz ; ( 2 ) 100Hz ; ( 3 ) 2/100Hz alternating frequency ; and ( 4 ) no treatment ( control group ) , respectively . Electric stimulation was applied over the anterior aspect of the dominant forearm for 30 minutes . MAIN OUTCOME MEASURES Mechanical pain thresholds ( MPTs ) and heat pain thresholds ( HPTs ) were recorded before , during , and after TENS stimulation . The data were analyzed using linear mixed models , with group treated as a between-subject factor and time a within-subject factor . RESULTS During and shortly after electric stimulation , HPT increased significantly in the alternating frequency stimulation group ( P=.024 ) . MPT increased significantly in both the 100Hz ( P=.008 ) and the alternating frequency groups ( P=.012 ) , but the increase was substantially larger in the 100Hz group . CONCLUSIONS Alternating frequency stimulation produced a greater elevation in the HPT , but a greater increase in the MPT was achieved using 100Hz stimulation This study examined the clinical effectiveness of high-frequency transcutaneous electrical nerve stimulation for reducing hypersensitivity of the h and . Nineteen patients suffering from h and hypersensitivity were r and omly assigned into either a treatment or a placebo group . A visual analogue scale and the Downey H and Centre H and Sensitivity Test were used to measure the tactile tolerance of the h and . Grip strength was assessed by a grip dynamometer . Daily applications of electrical stimulation were provided for 2 weeks . Significantly lower pain scores were found in the treatment group than in the placebo group by Day 7 and Day 11 . The ranking of ten dowel textures of the Downey H and Centre H and Sensitivity Test in the treatment group was significantly higher than in the placebo group by Day 7 and Day 11 . However , no significant intergroup difference was found in grip strength & NA ; In this pilot study , to assess the optimal stimulation parameters , 3 different forms of transcutaneous electrical nerve stimulation were performed in 27 patients . Conventional continuous stimulation with a constant frequency of 70 Hz , burst stimulation ( 90 msec trains of pulses with an internal frequency of 100 Hz repeated at 2 Hz , each train consisting of 10 pulses ) , and frequency‐modulated stimulation ( continuous pulses changed from 90 Hz to 55 Hz over 90 msec ) were r and omly delivered to the patients for half an hour in 3 separate sessions . The patients were blind to the modes of stimulation . This pilot study demonstrated that patients preferred modulated stimulation modes such as frequency modulation and burst rather than conventional constant mode This study is design ed to investigate the immediate effectiveness of electrotherapy on myofascial trigger points of upper trapezius muscle . Sixty patients ( 25 males and 35 females ) who had myofascial trigger points in one side of the upper trapezius muscles were studied . The involved upper trapezius muscles were treated with three different methods according to a r and om assignment : group A muscles ( n = 18 ) were given placebo treatment ( control group ) ; group B muscles ( n = 20 ) were treated with electrical nerve stimulation ( ENS ) therapy ; and group C muscles ( n = 22 ) were given electrical muscle stimulation ( EMS ) therapy . The effectiveness of treatment was assessed by conducting three measurements on each muscle before and immediately after treatment : subjective pain intensity [ ( PI ) with a visual analog scale ] , pressure pain threshold [ ( PT ) with algometry ] , and range of motion [ ( ROM ) with a goniometer ] of upper trapezius muscle ( lateral bending of cervical spine to the opposite side ) . When the effectiveness of treatment was compared with that of the placebo group ( group A ) , there was significant improvement in PI and PT in group B ( P < 0.01 ) but not in group C ( P > 0.05 ) . The improvement of ROM was significantly more in group C ( P < 0.01 ) as compared with that in group A or group B. When each group was divided into two additional subgroups based on the initial PI , it was found that ENS could reduce PI and increase PT significantly ( P < 0.05 ) , but did not significantly ( P > 0.05 ) improve ROM , as compared with the placebo group for both subgroups . EMS could significantly ( P < 0.05 ) improve ROM , but not PT , better than the placebo groups , for either subgroup . It could reduce PI significantly more ( P < 0.05 ) than placebo controls only for the subgroup with mild to moderate pain , but not with severe pain . For pain relief , ENS was significantly better ( P < 0.05 ) than EMS ; but for the improvement of ROM , EMS was significantly better ( P < 0.05 ) than ENS . It is concluded that ENS is more effective for immediate relief of myofascial trigger point pain than EMS , and EMS has a better effect on immediate release of muscle tightness than ENS OBJECTIVE To evaluate the effectiveness of transcutaneous electrical nerve stimulation ( TENS ) as a pain control method during office hysteroscopy . DESIGN A prospect i ve , r and omized study . SETTING Centre for Minimally Invasive Surgery , Department of Gynecological Science and Perinatology , " La Sapienza " University , Rome , Italy . PATIENT(S ) One hundred forty-two patients undergoing office hysteroscopy . INTERVENTION(S ) Application of a TENS device on the patient 's abdomen before and during office hysteroscopy . MAIN OUTCOME MEASURES The level of pain experienced by the patients was assessed using a 10 cm visual analog scale ; the side effects and changes in the hemodynamic parameters were evaluated . RESULT ( S ) The patients treated with TENS during hysteroscopy ( group A , n = 71 ) were compared with a control group ( group B , n = 71 ) on whom the TENS device was not used . The women in the TENS group experienced a significantly lower level of pain during hysteroscopy . No differences in side effects were observed between both group . CONCLUSION ( S ) TENS is a simple , efficient , and safe method of relieve pain during office hysteroscopy Abstract Ten patients with pain due to osteoarthritis of the knee were treated in a double‐blind cross‐over study with two weeks of transcutaneous electrical nerve stimulation ( TENS ) and placebo . There was statistically significant pain relief by TENS and half of the patients chose to continue using TENS for pain control after the test month . However , at one year 's follow‐up , only two patients had sufficient benefit to continue using the device The expectation of pain is a statistically significant factor negatively affecting patient compliance with current screening flexible sigmoidoscopy recommendations . Numerous pain reduction modalities have been studied with limited success . Transcutaneous electrical nerve stimulation ( TENS ) has been used to treat pain of various origins . The purpose of this pilot study was to determine the efficacy of TENS in reducing discomfort experienced during screening flexible sigmoidoscopy . A double-blind study was conducted in which 90 subjects were r and omized to receive TENS , sham TENS , or control ( st and ard care ) . The same pulse frequency and intensity were used for all subjects in the TENS group . Subjects completed preprocedural and postprocedural question naires , and the endoscopist completed a postprocedural question naire . A slight , but statistically insignificant ( p = .526 ) reduction in the mean pain score reported by the TENS group was noted when compared with the sham TENS and control groups ( 2.00 , 2.27 , and 2.23 respectively ) . In light of the fact that only one pulse frequency and intensity of the TENS intervention were used in this study , further study with this safe and cost-effective modality is warranted Objective This study was design ed to investigate the hypoalgesic effects of self-applied transcutaneous electrical nerve stimulation ( TENS ) on chronic low-back pain ( LBP ) in a multiple sclerosis ( MS ) population . Methods Ninety participants with probable or definite MS ( aged 21 to 78 y ) presenting with chronic LBP were recruited and r and omized into 3 groups ( n=30 per group ) : ( 1 ) low-frequency TENS group ( 4 Hz , 200 μs ) ; ( 2 ) high-frequency TENS group ( 110 Hz , 200 μs ) ; and ( 3 ) placebo TENS . Participants self-applied TENS for 45 minutes , a minimum of twice daily , for 6 weeks . Outcome measures were recorded at weeks 1 , 6 , 10 , and 32 . Primary outcome measures included : Visual Analog Scale for average LBP and the McGill Pain Question naire . Secondary outcome measures included : Visual Analog Scale for worst and weekly LBP , back and leg spasm ; Rol and Morris Disability Question naire ; Barthel Index ; Rivermead Mobility Index ; Multiple Sclerosis Quality of Life-54 Instrument , and a daily logbook . Data were analyzed blind using parametric and nonparametric tests , as appropriate . Results Results indicated a statistically significant interactive effect between groups for average LBP ( P=0.008 ) ; 1-way analysis of covariance did not show any significant effects at any time point once a Bonferonni correction was applied ( P>0.05 ) . However , clinical ly important differences were observed in some of the outcome measures in both active treatment groups during the treatment and follow-up periods . Discussion Although not statistically significant , the observed effects may have implication s for the clinical prescription and the use of TENS within this population & NA ; Part I of our earlier pilot study demonstrated that patients preferred modulated stimulation forms — frequency modulation and burst — rather than conventional continuous mode . To assess whether long‐term therapeutic effects vali date the immediate test results , this trial was performed in 14 patients with 21 pain conditions . Considering the results of the pilot study , the test stimulator was modified and 4 different forms of transcutaneous electrical nerve stimulation were r and omly delivered to each patient who was blind to the modes of stimulation for 20 min . A second observer assessed the pain scores using visual analogue scales . The stimulation modes employed were : ( 1 ) conventional continuous stimulation ( continuous pulses with a constant frequency of 70 Hz ) , ( 2 ) burst stimulation ( 80 msec long trains of pulses , each train consisting of 8 pulses , with an internal frequency of 90 Hz repeated 1.3 times a second ) , ( 3 ) high‐rate frequency modulation , HRFM ( continuous pulses changed from 90 Hz to 55 Hz over 90 msec , 1.3 times a second ) , ( 4 ) low‐rate frequency modulation , LRFM ( continuous pulses changed from 60 Hz to 20 Hz over 90 msec , 1.3 times a second ) . After the test treatment of 4 sessions in the clinic , depending on the pain scores and duration of pain relief recorded , the most effective stimulation mode was determined for each patient and a portable stimulator preset appropriately for that mode was given to be used at home , under our supervision , for 3 months . Fourteen pain conditions out of 21 ( 66 % ) responded well to the therapy ; the majority preferred was the HRFM and burst‐type stimulation . These results vali date the initial testing of different stimulation modes before assessing long‐term stimulation therapy In 23 patients with pancreatitis , daily pain for at least 3 months , and no abuse of alcohol , the pain-relieving effect of electroacupuncture ( 13 patients ) or transcutaneous electric nerve stimulation ( TENS ) ( 16 patients ) was studied . In two prospect i ve studies with a cross-over design , active acupuncture was compared with sham acupuncture , and TENS of the segmental points of the pancreas with sham treatment . Neither electroacupuncture nor TENS brought about pain relief that could substitute for or supplement medical treatment Objectives Transcutaneous electrical nerve stimulation ( TENS ) is primarily used for pain relief . However , evidence is beginning to emerge that TENS may also have a lowering effect on systemic blood pressure ( BP ) . The purpose of this study was to investigate the comparative effects of 2 intensities on pressure pain threshold ( PPT ) and resting BP in healthy humans , using low-frequency stimulation applied segmentally to the pain site . Methods In a double-blind design , 40 volunteers , stratified by sex , were r and omly allocated to 4 groups : high-intensity ( “ to tolerance without pain ” ) , low-intensity ( “ strong but comfortable ” ) , placebo , and control . TENS ( 2 Hz , 250 μ ) was applied over the distribution of the superficial radial nerve of the dominant h and for 30 minutes . The outcome variables were measured at baseline and at 6 subsequent 10-minute intervals . For the PPTs , 2 measurements were taken bilaterally from the first dorsal interosseous muscle using a pressure algometer . The BP was measured in the brachial artery with an automatic monitor . Data difference scores were analyzed using repeated- measures and 1-way analyses of variance . Results The high-intensity group showed a significant rise in PPT compared with the low-intensity , placebo , and control groups for both measurement sites , which sustained 30 minutes poststimulation . TENS produced no significant effect on BP , regardless of intensity . Discussion These results affirm that high levels of intensity are of fundamental importance in effective TENS dosage . This also applies for low frequency , segmental stimulation . Resting BP seems not to be dependent on intensity The therapeutic effect of once weekly transcutaneous electrical nerve stimulation in patients with rheumatoid arthritis was compared with placebo in a r and omised , double-blind , non-crossover study lasting three weeks . Thirty-two patients with classic or definite rheumatoid arthritis and wrist involvement were evaluated . Transcutaneous electrical nerve stimulation was better than the placebo in relieving pain at rest and while gripping . In addition , grip strength , measured as power and work done , immediately improved following transcutaneous electrical nerve stimulation but returned almost to initial values between assessment s. No significant improvement was shown for the placebo group OBJECTIVES To evaluate the efficacy of transcutaneous electrical nerve stimulation ( TENS ) for its effectiveness in eliminating or minimizing discomfort during office-based flexible cystoscopy . METHODS A total of 148 patients were prospect ively r and omized into one of three groups : flexible cystoscopy with no analgesics , a placebo TENS , or an activated TENS . The patient data collected included patient parameters , number of previous flexible cystoscopies , visual analog pain scores during and after the procedure , surgeon 's difficulty rating of procedure , and International Prostate Symptom Score before and 24 hours after the procedure . RESULTS No statistically significant difference was found among the three groups regarding patient parameters . The visual analog pain scores were similar before and after the procedure . At 30 seconds , the mean visual analog scale score for the control group , placebo group , and TENS study group was 3.73 , 3.65 , and 3.52 , respectively ( control versus placebo , control versus active , and placebo versus active : P = 0.97 , 0.29 , and 0.53 , respectively ) . At 1 and 5 minutes , the corresponding scores were 3.44 , 4.37 , and 3.50 ( P = 0.88 , P = 0.99 , and P = 0.99 ) and 0.86 , 1.23 , and 0.88 ( P = 0.97 , P = 0.35 , and P = 0.56 ) , respectively . The surgeon 's mean difficulty rating for the control procedures was 1.08 and for the placebo group was 2.30 ( P = 0.02 ) . CONCLUSIONS All patients undergoing flexible cystoscopy in the office setting experienced discomfort . The TENS device provided no significant benefit for pain . The trend toward greater pain scores in the control group could be attributed to the greater degree of difficulty The effect of transcutaneous nerve stimulation ( TNS ) was evaluated and compared with placebo TNS in 19 patients ( 17 women , mean age 33 years ) with orofacial functional pain and rheumatic disease involving the temporom and ibular joint . In two double-blind noncrossover experiments , high frequency TNS ( 100 Hz ) and low frequency TNS ( 2 Hz ) were evaluated by comparison of the patients ' functional and rest pain , muscle and joint tenderness , and jaw function . A significant treatment effect was obtained for all treatment methods regarding functional and rest pain and muscle and joint tenderness . None of the parameters except functional pain , which improved significantly more after high frequency TNS than placebo TNS , revealed any difference between the methods . Jaw function , however , revealed a few differences between high frequency TNS and placebo TNS |
1,644 | 29,130,623 | The results remained unchanged after the trim and fill method was applied to correct the bias .
In summary , higher body fatness at a young age may have a protective role in the later development of breast cancer in both premenopausal and postmenopausal women .
However , this potential benefit should not be overemphasized , as our findings suggest that increased body fatness gain from a young age is positively associated with postmenopausal breast cancer risk . | Higher body fatness in adulthood has been consistently associated with an increased risk of postmenopausal breast cancer , as well as a tendency towards a lower risk of premenopausal breast cancer .
However , the association between body fatness at a young age ( ≤30 years ) , body fatness gain and the risk of breast cancer is less defined . | In a large case – control study on breast cancer risk and serum hormone concentrations , nested within the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort , we examined to what extent the relationship of excess body weight with breast cancer risk may be explained by changes in sex steroids . Height , weight , waist and hip circumferences , and serum measurements of testosterone [ T ] , and rostenedione [ Δ4 ] , dehydroepi and rosterone sulphate [ DHEAS ] , estradiol [ E2 ] , estrone [ E1 ] and sex‐hormone binding globulin [ SHBG ] were available for 613 breast cancer cases , and 1,139 matched controls , who were all menopausal at the time of blood donation . Free T [ fT ] and free E2 [ fE2 ] were calculated using mass action equations . Breast cancer risk was related to body mass index ( BMI ) ( RR = 1.11 [ 0.99–1.25 ] , per 5 kg/m2 increase in BMI ) , and waist ( RR = 1.12 [ 1.02–1.24 ] , per 10 cm increase ) and hip circumferences ( RR = 1.14 [ 1.02–1.27 ] , per 10 cm increase ) . The increase in breast cancer risk associated with adiposity was substantially reduced after adjustment for any estrogens , especially for fE2 ( from 1.11 [ 0.99–1.25 ] to 0.99 [ 0.87–1.12 ] , from 1.12 [ 1.02–1.24 ] to 1.02 [ 0.92–1.14 ] and from 1.14 [ 1.02–1.27 ] to 1.05 [ 0.93–1.18 ] for BMI , waist and hip circumferences , respectively ) . A modest attenuation in excess risk was observed after adjustment for fT , but the remaining and rogens had little effect on the association of body adiposity with breast cancer . Our data indicate that the relationship of adiposity with breast cancer in postmenopausal women could be partially explained by the increases in endogenous estrogens , and by a decrease in levels of SHBG . © 2005 Wiley‐Liss , Introduction Overweight and obesity in childhood and adolescence are associated with reduced breast cancer risk , independent of adult body mass index ( BMI ) . These associations may be mediated through breast density . Methods We prospect ively examined associations of early life body fatness with adult breast density measured by MRI in 182 women in the Dietary Intervention Study in Children ( DISC ) who were ages 25–29 at follow-up . Height , weight , and other factors were measured at baseline ( ages 8–10 ) and annual clinic visits through adolescence . We used linear mixed-effects models to quantify associations of percent breast density and dense and non-dense breast volume at ages 25–29 with quartiles of age-specific youth body mass index ( BMI ) Z-scores , adjusting for clinic , treatment group , current adult BMI , and other well-established risk factors for breast cancer and predictors of breast density . Results We observed inverse associations between age-specific BMI Z-scores at all youth clinic visits and percent breast density , adjusting for current adult BMI and other covariates ( all p values < 0.01 ) . Women whose baseline BMI Z-scores ( at ages 8–10 years ) were in the top quartile had significantly lower adult breast density , after adjusting for current adult BMI and other covariates [ least squares mean ( LSM ) : 23.4 % ; 95 % confidence interval ( CI ) : 18.0 % , 28.8 % ] compared to those in the bottom quartile ( LSM : 31.8 % ; 95 % CI : 25.2 % , 38.4 % ) ( p trend < 0.01 ) . Significant inverse associations were also observed for absolute dense breast volume ( all p values < 0.01 ) , whereas there were no clear associations with non-dense breast volume . Conclusions These results support the hypothesis that body fatness during childhood and adolescence may play an important role in premenopausal breast density , independent of current BMI , and further suggest direct or indirect influences on absolute dense breast volume . Clinical Trials Registration NumberNCT00458588 ; April 9 , Greater body fatness during childhood is associated with reduced risk of premenopausal breast cancer , but few studies have addressed the relation of adiposity with sex hormones in girls . We prospect ively examined associations between adiposity and circulating levels of sex hormones and sex hormone – binding globulin ( SHBG ) among 286 girls in the Dietary Intervention Study in Children . Participants were 8 to 10 years old at baseline and were followed for an average of 7 years . Anthropometric measurements were taken at baseline and at subsequent annual visits , and blood sample s were collected every 2 years . Concentrations of dehydroepi and rosterone sulfate ( DHEAS ) during follow-up were higher among girls with greater body mass index ( BMI ) at baseline . The mean for the lowest BMI quartile was 63.0 μg/dL compared with 78.8 μg/dL for the highest quartile , and each kg/m2 increment in baseline BMI was associated with a 4.3 % increase ( 95 % confidence interval , 1.6 - 7.0 % ) in DHEAS levels during follow-up ( Ptrend = 0.002 ) . Concentrations of SHBG during follow-up were lower among girls with greater BMI at baseline . The mean for the lowest BMI quartile was 94.8 nmol compared with 57.5 nmol for the highest quartile , and each kg/m2 increment in baseline BMI was associated with an 8.8 % decrease ( 95 % confidence interval , 7.0 - 10.6 % ) in SHBG levels during follow-up ( Ptrend < 0.0001 ) . Estrogen and progesterone concentrations were similar across BMI quartiles . These findings suggest that adiposity may alter DHEAS and SHBG levels in girls . Whether and how these differences affect breast development and carcinogenesis requires further research . ( Cancer Epidemiol Biomarkers Prev 2007;16(9):1880–8 Abstract Obesity , physical inactivity , and sedentary behavior , concomitants of the modern environment , are potentially modifiable breast cancer risk factors . This study investigated the association of anthropometric measurements , physical activity and sedentary behavior , with the risk of incident , invasive breast cancer using a prospect i ve cohort of women enrolled in the Canadian Study of Diet , Lifestyle and Health . Using a case-cohort design , an age-stratified subcohort of 3,320 women was created from 39,532 female participants who returned completed self-administered lifestyle and dietary question naires at baseline . A total of 1,097 incident breast cancer cases were identified from the entire cohort via linkage to the Canadian Cancer Registry . Cox regression models , modified to account for the case-cohort design , were used to estimate hazard ratios ( HR ) and 95 % confidence intervals ( CI ) for the association between anthropometric characteristics , physical activity , and the risk of breast cancer . Weight gain as an adult was positively associated with risk of post-menopausal breast cancer , with a 6 % increase in risk for every 5 kg gained since age 20 ( HR 1.06 ; 95 % CI 1.01–1.11 ) . Women who exercised more than 30.9 metabolic equivalent task ( MET ) hours per week had a 21 % decreased risk of breast cancer compared to women who exercised less than 3 MET hours per week ( HR 0.79 ; 95 % CI 0.62–1.00 ) , most evident in pre-menopausal women ( HR 0.62 ; 95 % CI 0.43–0.90 ) . As obesity reaches epidemic proportions and sedentary lifestyles have become more prevalent in modern population s , programs targeting adult weight gain and promoting physical activity may be beneficial with respect to reducing breast cancer morbidity The prevalence of obesity at all ages is increasing epidemically worldwide . Information on the association between premenopausal breast cancer and body size during childhood and teenage years is scarce . In 1991 to 1992 , a prospect i ve cohort study was assembled in Norway and Sweden . We included in the analysis presented here 99,717 premenopausal women . During the follow-up period , which ended in December 1999 , 733 of these women developed a primary invasive breast cancer . Overweight and obesity [ body mass index ( BMI ) > 25 kg/m(2 ) ] at enrollment was associated with a decreased risk of premenopausal breast cancer ( P for linear trend = 0.007 ) . Apparent associations between perceived body shape at age 7 and BMI at age 18 , with heavier builds at both ages seemingly being protective for premenopausal breast cancer risk , lost their statistical significance after adjustment for BMI at cohort enrollment . Body size at age 7 was correlated with BMI at age 18 ( r = 0.43 ) ; BMI at age 18 was correlated with adult BMI ( r = 0.48 ) . Changes in body size from age 7 or 18 to adulthood did not affect per se risk of premenopausal breast cancer risk . Height was related to risk , with a statistically significantly 30 % reduced risk only in women shorter than 160 cm as compared with taller ones . The decreased risk of premenopausal breast cancer was observed in overweight and obese women without , but not in those with , a family history of breast cancer This study was conducted to assess the relation between body size and risk of breast cancer among young women . A case-control study was conducted among women aged 21 - 45 years living in three counties in Washington State . Cases were women born after 1944 with invasive or in situ breast cancer that was diagnosed between January 1 , 1983 , and April 30 , 1990 . Controls were selected using r and om digit dialing and were frequency-matched to cases on the basis of age and county of residence . Interviews took place between 1986 and 1992 . Body size was evaluated using indices from several different time periods . After adjustment for confounders , a decreased risk of breast cancer was found for women in the highest quintile of body mass index ( weight (kg)/height (m)2 ) as compared with the lowest quintile ( for maximum lifetime body mass index , odds ratio = 0.69 , 95 % confidence interval ( CI ) 0.51 - 0.94 ) . Age modified the relation between body size and risk of breast cancer . The odds ratio for women in the highest quintile of maximum body mass index who were aged 21 - 35 years was 0.29 ( 95 % CI 0.16 - 0.55 ) , as compared with an odds ratio of 1.5 for women aged 36 - 45 years ( 95 % CI 0.9 - 2.5 ) ( p for interaction = 0.003 ) . This study supports prior research showing a decreased risk of breast cancer associated with increased body size among premenopausal or young women . More detailed analysis in this study found a strong effect that was limited to the youngest age group ( < or = 35 years ) Few prospect i ve studies have investigated the association between BMI at age 20 years ( BMI 20y ) and breast cancer risk with consideration to estrogen/progesterone receptor status ( ER/PR ) . We evaluated the association between BMI 20y and ER/PR‐defined breast cancer risk among 41,594 women in the population ‐based Japan Public Health Center‐based Prospect i ve Study . Anthropometric factors were assessed using self‐reported question naires . Relative risks ( RRs ) were estimated by Cox proportional hazards regression models . Through to the end of 2006 , 452 breast cancer cases were identified . We observed a statistically significant inverse association between BMI 20y and breast cancer incidence [ multivariable‐adjusted RR for each 5‐unit increment 0.75 ( 95%CI = 0.61–0.92 ) ] , which was not modified by menopausal or recent BMI status . In contrast , recent BMI and subsequent BMI gain were not associated with increased risk among premenopausal women , but were substantially associated with increased risk among postmenopausal women [ corresponding RRrecent BMI = 1.31 ( 95%CI = 1.07–1.59 ) ; RRsubsequent BMI gain = 1.32 ( 95%CI = 1.09–1.60 ) ] . In subanalyses by receptor status ( ∼50 % of cases ) , the observed inverse association of BMI 20y with risk was consistent with the result for ER – PR– [ 0.49 ( 95%CI = 0.27–0.88 ) ] , while the observed positive associations of BMI gain with postmenopausal breast cancer risk appeared to be confined to ER+PR+ tumors [ corresponding RRfor subsequent BMI gain = 2.24 ( 95%CI = 1.50–3.34 ) ] . Low BMI at age 20 years was substantially associated with an increased risk of breast cancer . In contrast , high recent BMI and subsequent BMI gain from age 20 were associated with increased risk of postmenopausal ER+PR+ tumors OBJECTIVES We sought to determine whether social class modifies the effect of BMI on breast cancer incidence . METHODS Participants included 5642 postmenopausal White women recruited in 1989 to CLUE II , a prospect i ve cohort study in Washington County , Maryl and . We obtained exposure data from CLUE II and the 1990 US Census . We used survival and r and om-effects Cox proportional hazards analyses to determine the association of social class and BMI with breast cancer incidence . RESULTS Education was independently associated with increased risk of breast cancer incidence ( hazard ratio [HR]=1.06 ; 95 % confidence interval [CI]=1.01 , 1.11 ; P<.05 ) ; context ual measures of social class were not . Education modified the effect of BMI at age 21 years ( HR=0.98 ; 95 % CI=0.97 , 0.99 ) ; area-level social class modified the effect of BMI at baseline ( HR=0.97 ; 95 % CI=0.94 , 0.99 ) and BMI change ( HR=0.98 ; 95 % CI=0.95 , 1.00 ) . Sub population analyses that were adjusted for hormone use , parity , and breast-feeding found similar effects . CONCLUSIONS Social class moderates the influence of body size on breast cancer incidence . Public health efforts , therefore , should advocate for policies that improve social conditions to decrease the burden of breast cancer Obesity increases the risk of certain cancer types , e.g. , cancer of the endometrium , colon and gallbladder . For some other cancer forms , e.g. , prostate cancer , the association is less clear . We examined the association between body mass index ( BMI ) and hormone-dependent tumors , utilizing a cohort of 21,884 Swedish twins born during 1886 - 1925 . Information about BMI at different ages and potential confounding factors was collected prospect ively . The Swedish Cancer Registry was used to identify cases of cancer in the prostate ( n = 666 ) , breast ( n = 607 ) , corpus uteri ( n = 150 ) and ovary ( n = 118 ) during 1969 - 1997 . The material was analyzed as a traditional cohort and with co-twin control analyses that allow for control of genetic influences . Obesity ( BMI > /=30 kg/m(2 ) ) at baseline was positively associated with cancer in the corpus uteri [ relative risk ( RR ) = 3.03 , 95 % confidence interval ( CI ) 1.82 - 5.03 ] , as was BMI at age 25 , independently of BMI at baseline . Increased risk was also found for breast cancer but only in older women ( > /=70 years ) . Overweight at age 25 was associated with decreased risk of breast cancer ( RR = 0.51 , 95 % CI 0.33 - 0.78 ) . No association was found for prostate cancer . We conclude that age is an important effect modifier of cancer risk associated with obesity and that obesity and overweight in young adult life may affect cancer risk also later in life BACKGROUND A high body mass index ( BMI ) has been related to a reduced risk of breast cancer in premenopausal women . The mechanisms underlying this association have not been eluci date d. METHODS We explored whether factors affecting ovulation may explain the inverse association between BMI ( calculated as weight in kilograms divided by the square of height in meters ) and breast cancer in 113,130 premenopausal participants in the Nurses ' Health Study II . During 1,225,520 person-years of prospect i ve follow-up between 1989 and 2003 , 1398 incident cases of invasive breast cancer were diagnosed . Weight , height , ovulatory infertility , menstrual cycle patterns , and a multitude of covariates were assessed throughout follow-up . Cox proportional hazards regression was used to compute hazard ratios and 95 % confidence intervals ( CIs ) . RESULTS We observed a significant linear inverse trend between current BMI and breast cancer incidence ( P<.001 ) that was not explained by menstrual cycle characteristics or infertility due to an ovulatory disorder ( covariate-adjusted hazard ratio for breast cancer in women with a BMI > or = 30 vs 20.0 - 22.4 , 0.81 ; 95 % CI , 0.68 - 0.96 ) . We found BMI at age 18 years to be the strongest predictor of breast cancer incidence ( covariate-adjusted hazard ratio for breast cancer in women with a BMI at age 18 years > or = 27.5 vs 20.0 - 22.4 , 0.57 ; 95 % CI , 0.41 - 0.81 ) . CONCLUSIONS Body size during the early phases of adult life seems to be particularly important in the development of premenopausal breast cancer . Factors other than anovulation are likely to mediate the protection conferred by a high BMI We examined the relationship between body mass [ weight (kg)/height (m)2 ] and breast cancer using data from the Cancer and Steroid Hormone Study . The study compared 4323 women aged 20 - 54 years with newly diagnosed breast cancer identified through population -based tumor registries with 4358 women r and omly selected from the general population of the same geographic areas . Among naturally menopausal women , risk of breast cancer increased with increasing body mass index ( BMI ) ; those severely overweight ( BMI greater than or equal to 32.30 ) had nearly 3-fold higher risk of breast cancer compared with women in the leanest category ( BMI less than 20.00 ) . This positive association appeared stronger with increasing years since menopause and in women who had ever used estrogen replacement therapy . A positive association between body mass and breast cancer risk also was observed among premenopausal women ; however , risk estimates were substantially lower . Substantial weight gain from adolescence to adulthood was a more important risk factor than lifelong obesity . Prevalence of obesity increases with age ; our results suggest that interventions that prevent this trend could have an important effect on breast cancer risk , especially during the menopausal years The relation of body mass index ( BMI ) and weight gain to breast cancer risk is complex , and little information is available on Black women , among whom the prevalence of obesity is high . We assessed BMI and weight gain in relation to breast cancer risk in prospect i ve data from the Black Women 's Health Study . In 1995 , 59,000 African American women enrolled in the Black Women 's Health Study by completing mailed question naires . Data on anthropometric factors were obtained at baseline and every 2 years afterwards . In 10 years of follow-up , 1,062 incident cases of breast cancer occurred . Incidence rate ratios ( IRR ) were computed in multivariable Cox proportional hazards regression . BMI at age 18 years of ≥25 relative to < 20 was associated with a reduced risk of breast cancer among both premenopausal women ( IRR , 0.68 ; 95 % confidence interval , 0.46 - 0.98 ) and postmenopausal women ( IRR , 0.53 ; 95 % confidence interval , 0.35 - 0.81 ) . There was an inverse association of current BMI with premenopausal breast cancer but no association with postmenopausal breast cancer , either overall or among never-users of hormone therapy . Weight gain was not associated with postmenopausal breast cancer risk . In analyses restricted to breast cancers that were estrogen and progesterone receptor positive , IRRs for current BMI and weight gain were elevated but not statistically significant . The findings indicate that being overweight at age 18 years is associated with a reduced risk of both premenopausal and postmenopausal breast cancer in African American women . Underst and ing the reasons for the association may help eluci date the pathways through which adolescent exposures influence breast cancer risk . The lack of association of obesity with receptor-negative tumors in postmenopausal African American women may partially explain why breast cancer incidence in older Black women is not high relative to other ethnic groups in spite of the high prevalence of obesity in Black women . ( Cancer Epidemiol Biomarkers Prev 2007;16(9):1795–802 OBJECTIVE To investigate the association between anthropometry and risk of breast cancer among pre- and post-menopausal women in urban Shanghai . METHODS A total of 73 461 female residents aged 40 to 70 years in urban Shanghai were recruited in a prospect i ve cohort study ( the Shanghai women 's health study ) during 1997 through 2000 , and were actively followed up biennially . During mean follow-up period of 5.66 years , 432 incident cases of breast cancer were identified in the cohort . Cox regression model was used to estimate the adjusted relative risks ( RRs ) and 95 % confidence intervals ( CIs ) . RESULTS After adjustment for some potential confounding factors , baseline weight , body mass index ( BMI ) , waist-to-hip ratio(WHR ) and weight gain since age 20 were positively associated with the increased risk of breast cancer among postmenopausal women . The positive association between height and breast cancer was found among premenopausal women . Among them , those with height taller than 161 cm at age 20 experienced 1.84 fold increased risk ( 95 % CI : 1.30 - 2.61 ) of breast cancer compared to their counterpart with height shorter than 157.1 cm . Women who were either much heavier or lighter than average at age 20 were at reduced risk . Further analyses mutually adjusted for BMI and WHR did not substantially alter the positive association for both BMI and WHR . After further adjustment for BMI , weight gain since age 20 was significantly associated to an increased risk for postmenopausal breast cancer ( RR = 1.61 , 95 % CI : 1.09 - 2.37 ) . CONCLUSIONS Weight gain and central obesity seemed to be strong predictors for the risk of breast cancer among postmenopausal women . Controlling weight and decreasing fat around waist were effective means to prevent postmenopausal breast cancer and height might serve as a risk factor for premenopausal breast cancer |
1,645 | 17,443,629 | Health research ers using postal question naires can increase response rates using the strategies shown to be effective in this systematic review | BACKGROUND Postal question naires are widely used for data collection in epidemiological studies but non-response reduces the effective sample size and can introduce bias .
Finding ways to increase response rates to postal question naires would improve the quality of health research .
OBJECTIVES To identify effective strategies to increase response rates to postal question naires .
SEARCH STRATEGY We aim ed to find all r and omised controlled trials of strategies to increase response rates to postal question naires . | The objective of this study was to compare the impact of closed- versus open-ended question formats on the completeness and accuracy of demographic data collected in a mailed survey question naire . We surveyed general internists in five Canadian provinces to determine their career satisfaction . We r and omized respondents to receive versions of the question naire in which 16 demographic questions were presented in a closed-ended or open-ended format . Two questions required respondents to make a relatively simple computation ( ensuring that three or four categories of response added to 100 % ) . The response rate was 1007/1192 physicians ( 80.0 % ) . The proportion of respondents with no missing data for all 16 questions was 44.7 % for open-ended and 67.0 % for closed-ended formats ( P < 0.001 ) . The odds of having missing items remained higher for open-ended response options after adjusting for a number of respondent characteristics ( 2.67 , 95 % confidence interval 2.01 to 3.55 ) . For the two questions requiring computations focused on professional activity and income , there were more missing data ( P = 0.02 , 0.02 , respectively ) but fewer inaccurate responses ( P = 0.009 , 0.20 , respectively ) for the open-ended compared to the closed-ended format . Investigators can achieve higher response rates for demographic items using closed format response options , but at the risk of increasing inaccuracy in response to questions requiring computation STUDY OBJECTIVE --The aim of the study was to determine whether complete anonymity improves the response rates to a postal question naire . DESIGN --The study derived from a series of postal surveys on AIDS knowledge conducted on six different date s in 1986 and 1987 . The sample was r and omly divided into two , each group being sent the same question naire . One group was informed that the replies were anonymous , the other that they were not . The latter were sent reminders . SETTING --Recipients of the question naires were drawn from the Southampton electoral rolls . PARTICIPANTS --300 people in each survey ( total 1800 ) were sent question naires , representing on each occasion a different 1:500 systematic sample . RESULTS --Response rate was 49 % for the anonymous question naires and 51 % for the numbered question naires . Reminders boosted the response in the numbered group to 72 % . CONCLUSIONS --There is no evidence that anonymity improves response to postal question naires , but the use of reminders may do so Postal health surveys in the general population can provide important information to assist with planning and service provision . 1 High response rates are needed to ensure validity and to minimize costs from following-up non-responders . 2 Only a small number of studies have examined methods to increase response rates in postal surveys . Using a post-office stamp rather than a prepaid business reply envelope may seem more personal and encourage participants to return the question naire . However , results from trials evaluating this are inconsistent and limited to health professionals in North America . 3–5 Consequently there is little evidence to inform the choice of reply envelopes in postal surveys of the general UK population . This was determined in the current study . Methods The sample consisted of 633 adults r and omly selected from a health authority register in the north west of Engl and . A computer-generated r and omization list , stratifying on sex and age ( 18–45 , 46–64 , у65 years ) was used to allocate participants to receive one of two types of reply envelopes , both printed with the return address . One group ( POS ) received a reply envelope with a first-class post-office stamp , while the second group ( PPB ) received a prepaid business-franked envelope to return their health question naire . The initial mail-out included the 16-page health question naire , a personalized letter from the Director of Public Health and one of the two return envelopes . Question naires were sent out in March 2001 and non-responders were sent a reminder postcard 10 days later . The primary outcome was the difference in response rates between the two types of reply envelopes , after follow-up reminders had been sent measured at 4 weeks after posting the survey . The χ 2 test was used to examine statistical significance . Approval was obtained for the study from the Local Research Ethics Committee.2 % ) question naires were returned within 10 days , from the two allocation groups , respectively . After sending reminders to the 182 non-responders in the POS group and 195 in the PPB group ( excluding 6 and 4 participants respectively later found to be not living at that address ) , the return rate increased to 182 ( 58.7 % ) and 179 ( 57.2 % ) in the two groups . This difference of 1.5 % between the two groups is unlikely to be important and was not statistically significant ( χ 2 = 0.08 , P = 0.77 ) . No important difference was observed in return rates between the POS and the PPB group for men or women and across three age groups . However , return rates Mailing surveys to low-income population s is often avoided because of concern about low response rates . In this study , the authors used a mailed survey of a low-income population to test whether $ 1.00 or $ 2.00 cash-response incentives were worth the expense and whether 2-day priority mail ( $ 2.90 postage ) would yield a sufficiently higher response rate than certified mail ( $ 1.52 postage ) to justify its cost . In 1994 , 2,243 r and omly selected families in subsidized health care programs in Pierce County , Washington , were r and omly sent no incentive , $ 1.00 , or $ 2.00 in the first of three mailings . For the third mailing , nonrespondents were r and omly assigned to receive either certified or 2-day priority mail . After 4 weeks , the response rates were 36.7 % , 48.1 % , and 50.3 % for the no-incentive , $ 1.00 , and $ 2.00 groups , respectively . After three mailings , the cost per response was the lowest for the group that received $ 1.00 . The response rate for the certified mailing ( 28.1 % ) was significantly higher than the rate for the more expensive priority mailing ( 21.7 % ) . No incentive-related bias was detected . The authors concluded that the most efficient protocol for this low-income population was to use a $ 1.00 incentive in the first mailing and a certified third mailing OBJECTIVES The effects of incentive size on physicians ' response rates to a mail survey were determined . METHODS One thous and US primary care physicians were assigned r and omly to receive a survey with either a $ 5 bill or a $ 2 bill as an incentive . For each of the two incentive groups , the overall response rate for three mailing waves , the total cost , and the total cost per usable response were measured . RESULTS The response rate among those receiving the $ 5 bill ( 61 % ) was 32 % higher than the response rate among those receiving the $ 2 bill ( 46 % ) ; overall costs were slightly higher in the $ 5 group , but the cost per response for each group was similar ( $ 15.46 versus $ 14.93 ) . For the same cost , a higher response rate could have been achieved in the $ 2 group if costs saved from foregoing the third mailing were instead used to increase the incentive for a portion of the subjects . CONCLUSIONS A $ 5 bill incentive yielded a higher response rate among the physicians in this study than did a $ 2 bill incentive . Moreover , the powerful effect of the incentive size , combined with the consequent decline in the costs of subsequent mailing waves , suggests that re sources in a fixed survey budget are allocated more efficiently to increasing the initial incentive rather than to providing a third wave to nonresponders We studied women 45 - 54 years of age from two communities who failed to return a mailed survey in an experiment to assess the impact on interviewing response rates of leaving messages on telephone answering machines at the time of telephone follow-up . There were 88 and 103 subjects assigned to the " message " and " no message " groups , respectively . After adjustment for age , interviewer , and community , leaving messages increased the rate of reaching a household by about 15 % and improved the overall interviewing response rate by about 15 % as well . This improvement was more apparent in women from the higher socioeconomic status community Study objective : To assess the effectiveness of a telephone reminder in increasing responses to postal surveys and to calculate the differential costs per completed question naire . Design : R and omised controlled trial . Setting : Australian university and rehabilitation medicine practice . Participants : The trial was conducted in 1999 among the 143 non-respondents to a question naire about work related neck and upper body disorders . The question naire was sent to two Australian female sample s : 200 office workers ( Sample A ) and 92 former rehabilitation medicine patients ( Sample B ) . A reminder letter , another copy of the question naire and a final letter were sent at two week intervals . Half of the non-respondents within each sample were r and omly selected to receive a telephone reminder just after the second mailout of the question naire . All direct costs were calculated . Main results : Responses were significantly higher among those who received the telephone reminder intervention ( relative risk 2.54 , 95 % confidence intervals 1.43 to 4.52 ) . Analysed by intention to phone , 47 % of non-respondents in Sample A and 38 % in Sample B returned a complete question naire after the intervention , compared with 21 % and 10 % , respectively , in the control groups . For the 112 women ( combined sample s ) who returned completed question naires before r and omisation , the average cost per respondent was AUD14 . There was a higher total cost for the intervention groups ( AUD851 versus AUD386 for controls ) , but the significantly higher number of additional completed responses ( 31 versus 12 ) result ed in a 15 % lower marginal cost per completed question naire in those groups . Conclusion : Telephone reminders are cost effective in improving responses to postal surveys OBJECTIVES To assess the impact of patient satisfaction survey method on response rate , data quality and satisfaction . PATIENTS AND METHODS Four modes of data collection were assessed during a r and omized trial that included 400 in patients discharged from a teaching hospital . RESULTS The response rate was 58 % within the mail survey group ( 72 % with follow-up letter ) versus 73 % and 81 % within the home and telephone interview group ( p < 0.01 ) . 69 % of the mailed question naires contained no missing values versus 94 % and 96 % for home and telephone interview modes ( p < 0.01 ) . The global satisfaction scale score was greater within the mail survey groups ( 8.1/10 without follow-up letter and 7.9 with follow-up letter ) than within the telephone interview group ( 7.8 ) and the face to face interview group ( 7.3 ) , ( p < 0.05 ) . CONCLUSION Mail survey with follow-up letter constitutes an operational method despite lower data quality and overestimation of patients ' satisfaction scores Although self-administered question naires are major sources of information in epidemiology , comparatively little has been done to study practical aspects of design and mailing . The objective of this study was to evaluate various measures taken to increase the response rate . A question naire was mailed in July 1995 to a r and om sample ( n = 2,000 ) of the Swedish population aged 20 - 79 years . Using a r and omized factorial study design , the question naire and mailing procedures were changed in three ways : preliminary notification , length of the question naire , and mention of telephone contact . The overall question naire retrieval rate was 49 % . Preliminary notification ( adjusted odds ratio of receiving a completed question naire = 1.30 , 95 % confidence interval ( CI ) 1.08 - 1.56 relative to the absence of preliminary notification ) and short length of the question naire ( odds ratio = 1.24 , 95 % CI 1.04 - 1.48 relative to a long question naire ) were both independently associated with a higher retrieval rate . Of eight possible combinations , the one comprising preliminary notification , a short question naire , and no mention of telephone contact gave the highest retrieval rate , 56 % . The lowest retrieval rate , 40 % , was observed for the combination of no preliminary notification , a long question naire , and mention of telephone contact . Young age , male sex , and urban residence significantly lowered the retrieval rate . Although there was a positive association between the question naire retrieval rate and partial nonresponse ( missing answers in retrieved question naires ) , the marginal losses due to the latter did not cancel the gains by optimized mailing routines . Old age was the strongest determinant of partial nonresponse . The data provide evidence that design and mailing strategies , as well as demographic characteristics , may greatly influence the response rate of mailed epidemiologic question naires BACKGROUND A range of factors have been shown to affect the response rate to mailed question naires , but particular strategies to improve patients ' response in trials conducted in general practice require further study . METHODS Non-responders in a larger trial were r and omized to receive a telephone or recorded delivery reminder on the third contact . The cost of administration of each method was estimated . RESULTS Significantly more patients returned completed question naires when sent question naires by recorded delivery , although the cost per patient contacted was nearly three times more than for contact by telephone . CONCLUSION Our study indicates that sending reminders by recorded delivery , although more expensive , is more effective than telephone reminders for recruiting patients to a study in general practice using research question naires In two experiments , findings with college undergraduates ( Ns = 154 and 137 ) suggest social desirability may not affect responses to survey items on HIV-related behaviors and results may not be constrained by anonymity In this study , the authors sought to determine the effects of length and clarity on response rates and data quality for two food frequency question naires ( FFQs ) : the newly developed 36-page Diet History Question naire ( DHQ ) , design ed to be cognitively easier for respondents , and a 16-page FFQ developed earlier for the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial . The PLCO Trial is a 23-year r and omized controlled clinical trial begun in 1992 . The sample for this sub study , which was conducted from January to April of 1998 , consisted of 900 control and 450 screened PLCO participants aged 55 - 74 years . Controls received either the DHQ or the PLCO FFQ by mail . Screenees , who had previously completed the PLCO FFQ at baseline , were administered the DHQ . Among controls , the response rate for both FFQs was 82 % . Average amounts of time needed by controls to complete the DHQ and the PLCO FFQ were 68 minutes and 39 minutes , respectively . Percentages of missing or uninterpretable responses were similar between instruments for questions on frequency of intake but were approximately 3 and 9 percentage points lower ( p < or = 0.001 ) in the DHQ for questions on portion size and use of vitamin/mineral supplements , respectively . Among screenees , response rates for the DHQ and the PLCO FFQ were 84 % and 89 % , respectively , and analyses of questions on portion size and supplement use showed few differences . These data indicated that the shorter FFQ was not better from the perspective of response rate and data quality , and that clarity and ease of administration may compensate for question naire length In a follow-up study , only 64 % of 126,628 US radiologic technologists completed a question naire during 1994 - 1997 after two mailings . The authors conducted a r and omized trial of financial incentives and delivery methods to identify the least costly approach for increasing overall participation . They r and omly selected nine sample s of 300 nonresponders each to receive combinations of no , 1.00 US dollar , 2.00 US dollars , and 5.00 US dollars cash or check incentives delivered by first-class mail or Federal Express . Federal Express delivery did not achieve greater participation than first-class mail ( 23.2 % vs. 23.7 % ) . In analyses pooled across delivery methods , the response was significantly greater for the 2.00 US dollar bill ( 28.9 % , 95 % confidence interval ( CI ) : 25.2 , 32.7 ; p < 0.0001 ) , 5.00 US dollars check ( 27.5 % , 95 % CI : 22.5 , 33.0 ; p = 0.0001 ) , 1.00 US dollar bill ( 24.6 % , 95 % CI : 21.2 , 28.3 ; p = 0.0007 ) , and 2.00 US dollars check ( 21.8 % , 95 % CI : 18.5 , 25.3 ; p = 0.02 ) compared with no incentive ( 16.6 % , 95 % CI : 13.7 , 19.9 ) . The response increased significantly with increasing incentive amounts from 0.00 to 2.00 US dollars cash ( p trend < 0.0001 ) . The 2.00 US dollar bill achieved a 30 % greater response than did a 2.00 US dollars check ( p = 0.005 ) . For incentives sent by first-class mail , the 5.00 US dollars check yielded 30 % greater participation than did the 2.00 US dollars check ( p = 0.07 ) . A 1.00 US dollar bill , chosen instead of the 2.00 US dollars bill because of substantially lower overall cost and sent by first-class mail to the remaining 42,717 nonresponders , increased response from 64 % to 72 % The purpose of this study was to investigate how response rates to a postal question naire are affected by title and length of the survey instrument . Five question naires , which differed according to title and length , were design ed . Each question naire was mailed to a r and om sample of one thous and Norwegian women aged , 35—49 years . A total of 3,106 question naires were returned ( 62.1 % ) . The highest response rate ( 70.2 % ) was achieved by a two-page question naire entitled ` ` Women and Cancer ' ' . An otherwise identical question naire entitled ` ` Oral Contraceptives and Cancer ' ' had a response rate of 60.7 % . Question naires entitled ` ` Women and Cancer ' ' with a length of four and six pages had a response rate of 62.8 % and 63.3 % , respectively . The four page question naire entitled ` ` Women , Lifestyle and Health ' ' had the lowest response rate of 57.1 % . This study shows that in a general population of Norwegian women the title of a postal question naire influences the response rate . The results indicate that although the shortest question naire had the highest response rate , the most extensive survey instrument did not have the lowest response rate . The distribution of risk factors for breast cancer did not vary according to response rate or design of question naire . The overall findings of this study suggest that the benefits from the increased information obtained from extensive postal question naires out-weighs a potential non-response bias due to a somewhat lower response rate In 1989 , the authors tested the effectiveness of two response-enhancing techniques , a postage stamped or franked return envelope and a prenotification letter , in a survey of pregnancy among 10,047 resident physicians in the United States . The techniques were r and omly assigned using a factorial design . No significant interactions were observed between the techniques . After two mailings , those who received a stamped return envelope had a response of 71.2 % , compared with 68.2 % for those who received a franked return envelope ( 95 % confidence interval 1.3 - 4.9 % ) . Men who received the stamped envelope had a 5.9 % greater response than those who received the franked envelope ( p less than 0.001 ) , but the type of postage did not influence response among women ( p = 0.84 ) ; this interaction was statistically significant ( p = 0.006 ) . Physicians who received a prenotification letter had a response of 69.0 % , compared with 70.5 % for those who did not receive the letter ( 95 % confidence interval -3.3 to 0.2 % ) . The authors conclude that seemingly minor changes in survey design could have saved from 12 % to 19 % of the total cost of the study Young adults who had previously participated in a longitudinal survey of youth were sent a question naire . They were r and omly assigned to receive a $ 20 prepayment , a $ 20 postpayment , or a $ 25 postpayment for participation in the latest survey . Those in the large incentive condition were 7 percentage points more likely to return a survey than those in the smaller , postpayment group . Prepayment had a smaller , less reliable effect . Effects of incentive magnitude and timing were consistent at each month of the study period ; only better high school grade s distinguished early responders from late responders . Nonresponders had characteristics suggestive of low social conformity and were more likely than responders to be African American and male and have low SES . The discussion centers on motivations for participating in research and differences in the incentives likely to promote continued response versus initial study enrollment Insufficient response rates are a frequent problem in mailed epidemiologic health surveys . As part of a health survey of 1,235 young adults conducted from November 1992 through January 1993 in Geneva , Switzerl and , a r and omized factorial trial was carried out to assess the contributions of two tactics to increase response rates . The first incentive was the promise of sending 10 Swiss francs ( 7 US dollars ) to respondents ; the second was a red postcard , mailed 2 days after the question naire , which reminded potential participants to complete the question naire . The most effective strategy according to interim analysis was to be selected for follow-up mailings . Two weeks after the first mailing , response rates were 65 % for those who had received both incentives , 57 % for those who had been offered the money reward only , 54 % for recipients of the reminder card , and 48 % for those who had received neither incentive ( p based on chi 2 ( 3 df ) test < 0.001 ) . The relative hazards of responding were 1.34 ( 95 % confidence interval 1.15 - 1.55 ) for the money reward and 1.22 ( 95 % confidence interval 1.05 - 1.41 ) for the reminder card . Follow-up mailings to all nonrespondents included both incentives . At the end of data collection , 1,007 persons ( 82 % ) had returned the question naire . The final response rates were 83 , 84 , 82 , and 78 % in the four groups , respectively ( p = 0.29 ) . Both the promise of a monetary reward and a reminder postcard considerably improved early response rates . The use of both incentives in follow-up mailings brought final response rates above 80 % , except for those who had received no initial incentive . Testing various combinations of incentives in the early stages of a mailed health survey may be a generally useful strategy To evaluate response‐aiding strategies feasible in large surveys , we r and omly allocated general practitioners ( GPs ) to one of four intervention groups : Group 1 received ‘ exhaustive ’ telephone prompts by a medical peer in advance of a question naire ; Group 2 , inclusion of an embossed pen with the question naire ; Group 3 , an advance letter prompt ; and Group 4 , a ‘ single attempt ’ advance telephone prompt by a non‐medical research assistant . Follow‐up procedures were identical . Response rates by group were not significantly different overall ( χ24.59 , df=3 , p=0.20 ) although advance prompts by a medical peer were significantly more effective than other strategies for male GPs . The difference in overall response rates between males ( 63 % ) and females ( 74 % ) was significant ( χ2=15.40 , df=1 , p<0.01 ) . No other response bias was evident . Our demonstration of a significant interaction between respondent sex and response‐aiding strategy invites further research BACKGROUND Low response rates are acknowledged as a potential source of bias in survey results . Response rates are a particular problem in surveys of GPs . Thus , the methods used to encourage response to mailed surveys and the influence of inducements in maximizing response rates are fundamental issues to be examined when addressing the problem of response bias . AIM To increase the overall response rate to a national study of GPs and to explore the effects of financial and non-financial inducements on response rates . METHODS Two mailing waves of a postal question naire to a 20 % r and om sample of all GPs in Engl and and Wales had achieved a 33 % response rate . For the third mailing wave , the non-responding GPs were then divided into a control group , a group who were offered a donation to charity to complete the question naire and a group who were offered cash . The charity and cash groups were further subdivided into 5 pounds and 10 pounds groups to assess the effect of the size of the inducement offered . For the control group , a fourth wave was sent the offer of a 5 pounds or 10 pounds incentive . RESULTS Response was positively affected by the offer of an inducement . Cash , however , had a more substantial effect than the offer of a donation to charity . Older GPs were less likely to participate overall , whereas male GPs were more likely to respond to a cash inducement . Doctors who had seen more patients were less likely to reply earlier and were more likely to respond to the offer of cash . CONCLUSIONS Primary care is going through many changes , some of which have increased the workload of the GP . It may now be that , to achieve the response rates needed to vali date policy-related research , the offer of inducements will become a necessary part of the research process Low response rates , especially among physicians , are a common problem in mailed survey research . We conducted a r and omized trial to examine the effects of cash and lottery incentives on response rates . A total of 4,850 subjects were r and omized to one of three interventions accompanying a mailed survey-no incentive ( n = 1,700 ) , cash payment [ three levels of Hong Kong dollars ( HKD ) $ 10 , $ 20 , and $ 40 ; N = 50 in each subgroup ] , or entry into a lottery ( three levels of HKD$1,000 , $ 2,000 , and $ 4,000 ; N = 1,000 in each subgroup ) on receipt of the completed question naire . The response rates were higher among those offered incentives than those without ( 19.8 % vs. 16.8 % , P = .012 ) . Cash was the more effective incentive compared to lottery ( 27.3 % vs. 19.4 % , P = .017 ) . Response also increased substantially between the first and second mailings ( 14.2 % vs. 18.8 % , P > .001 ) . In addition , those with specialist qualifications were more willing to participate in mailed surveys . We found no significant differences in response outcomes among the various incentive arms . Cash reward at the $ 20 level was the most cost-effective intervention , in terms of cost per responder . Further systematic examination of the effects of different incentive strategies in epidemiologic studies should be encouraged Background Postal question naires are an economical and simple method of data collection for research purpose s but are subject to non-response bias . Several studies have explored the effect of monetary and non-monetary incentives on response . Recent meta-analyses conclude that financial incentives are an effective way of increasing response rates . However , large surveys rarely have the re sources to reward individual participants . Three previous papers report on the effectiveness of lottery incentives with contradictory results . This study aim ed to determine the effect of including a lottery-style incentive on response rates to a postal health survey . Methods R and omised controlled trial . Setting : North and West Birmingham . 8,645 patients aged 18 or over r and omly selected from registers of eight general practice s ( family physician practice s ) . Intervention : Inclusion of a flyer and letter with a health question naire informing patients that returned question naires would be entered into a lottery-style draw for £ 100 of gift vouchers . Control : Health question naire accompanied only by st and ard letter of explanation . Main outcome measures : Response rate and completion rate to question naire . Results 5,209 individuals responded with identical rates in both groups ( 62.1 % ) . Practice , patient age , sex and Townsend score ( a postcode based deprivation measure ) were identified as predictive of response , with higher response related to older age , being female and living in an area with a lower Townsend score ( less deprived ) . Conclusion This RCT , using a large community based sample , found that the offer of entry into a lottery style draw for £ 100 of High Street vouchers has no effect on response rates to a postal health question naire OBJECTIVES To assess the effect of incentive size on response rates , data quality , and cost in a digestive health status mail survey of a community sample of health plan enrollees . DATA SOURCES / SETTING The study population was selected from a data base of enrollees in various health plans obligated to receive care at Park Nicollet Clinic-HealthSystem Minnesota , a large , multispecialty group in Minneapolis , Minnesota , and the nearby suburbs . STUDY DESIGN A total of 1,800 HealthSystem Minnesota enrollees were r and omly assigned to receive a survey with an incentive of $ 5 or $ 2 . The response rates for each incentive level were determined . Data quality , as indicated by item nonresponse and scale scores , was measured . Total cost and cost per completed survey were calculated . PRINCIPAL FINDINGS The response rate among enrollees receiving $ 5 ( 74.3 percent ) was significantly higher than among those receiving $ 2 ( 67.4 percent ) ; differences were more pronounced in the first wave of data collection . Data quality did not differ between the two incentive groups . The total cost per completed survey was higher in the $ 5 condition than in the $ 2 condition . CONCLUSIONS A $ 5 incentive result ed in a higher response rate among a community patient sample with one mailing than did a $ 2 incentive . However , the response rates in the $ 2 condition approached the level of the $ 5 incentive , and costs were significantly lower when the full follow-up protocol was completed . Response rates were marginally increased by follow-up phone calls . The incentive level did not influence data quality . The results suggest if a survey budget is limited and a timeline is not critical , a $ 2 incentive provides an affordable means of increasing participation Background Response rates to surveys are declining and this threatens the validity and generalisability of their findings . We wanted to determine whether paper quality influences the response rate to postal surveys Methods A postal question naire was sent to all members of the British Society of Gynaecological Endoscopy ( BSGE ) . Recipients were r and omised to receiving the question naire printed on st and ard quality paper or high quality paper . Results The response rate for the recipients of high quality paper was 43/195 ( 22 % ) and 57/194 ( 29 % ) for st and ard quality paper ( relative rate of response 0.75 , 95 % CI 0.33–1.05 , p = 0.1 Conclusion The use of high quality paper did not increase response rates to a question naire survey of gynaecologists affiliated to an endoscopic society DESIGN : To assess the feasibility of conducting a re-survey of men who are resident in the United Kingdom 25 years after enrollment in the Whitehall study of London Civil Servants . METHODS : A r and om sample of 401 study survivors resident in three health authority areas was selected for this pilot study . They were mailed a request to complete a self administered question naire , and then asked to attend their general practice to have their blood pressure , weight , and height measured and a blood sample collected into a supplied vacutainer , and mailed to a central laboratory . Using a 2 x 2 factorial design , the impact of including additional questions on income and of an informant question naire on cognitive function was assessed . RESULTS : Accurate addresses were obtained from the health authorities for 96 % of the sample . Question naires were received from 73 % and blood sample s from 61 % of the sample . Questions on income had no adverse effect on the response rate , but inclusion of the informant question naire did . Between 1970 and 1995 there were substantial changes within men in the mean blood pressure and blood total cholesterol recorded , as reflected by correlation coefficients between 1970 and 1995 values of 0.26 , and 0.30 for systolic and diastolic blood pressure and 0.38 for total cholesterol . CONCLUSION : This pilot study demonstrated the feasibility of conducting a re-survey using postal question naires and mailed whole blood sample s. The magnitude of change in blood pressure and blood total cholesterol concentrations within individuals was greater than anticipated , suggesting that such re measurements may be required at different intervals in prospect i ve studies to help interpret risks associations properly . These issues will be considered in a re-survey of the remaining survivors of the Whitehall study The purpose of this research was to study the effect of various direct mail techniques on professional nurses ' response rates to question naires . A r and om sample of 700 registered professional nurses consisting of five groups who were members of New York State Nurses Association ( NYSNA ) were mailed a question naire with 22 items . The study demonstrated that the response rates were directly attributable to techniques used . Providing information about the association was related to significantly decreased response rates and monetary incentives with significantly increased response rates . A combined direct mailing for question naire completion and membership solicitation was not effective for either purpose PURPOSE To investigate the impact on subject response of an information brochure and cash incentives included with mailed question naires in case-control studies . METHODS A r and omized trial was carried out within a case-control study investigating cancer in the Province of Ontario . Brochures were included with half of the mailed question naires sent to 7487 cases and 2561 controls . Controls were also sent cash incentives of $ 2 , $ 5 , or no money . RESULTS With the brochure , response changed from 75.0 % to 75.8 % in cases , and from 70.3 % to 71.1 % in controls . Adjusting for differences in age , residence , sex , and cancer site/status , the change was 0.2 % [ 95 % confidence interval ( CI ) = -1.7 - 2.1 ] in cases , and 0.6 % ( 95 % CI = -3.1 - 4.3 ) in controls . The $ 2 and $ 5 incentives increased overall response in controls from 61.9 % to 72.8 % and 77.2 % , respectively , i.e. , by 10.9 % ( 95 % CI = 6.1 - 15.6 ) and 15.1 % ( 95 % CI = 10.4 - 19.7 ) , after adjustment . This effect was largely confined to urban areas ( for $ 2 and $ 5 , respectively : 5.5 % and 14.2 % in Toronto , 15.3 % and 20.4 % in other urban areas vs. 2.7 % and 1.0 % in rural areas ; p = 0.02 ) . Response time showed little or no improvement when the brochure was included , but was markedly reduced for both the $ 2 and $ 5 incentives . CONCLUSIONS Cash incentives can improve subject response in epidemiologic studies , whereas information brochures do not appear to have an effect Objective : This study measures the effect of an intervention to improve mailed survey response rates Mail surveys have been used to follow-up early participants in a Canadian breast cancer prevention trial . To minimize non-response bias , we undertook a r and omized study of two postal strategies , of which one was our usual procedure and the other was a systematic application , known as the total design method ( TDM ) and described by Dillman . The response rates to the two methods were 62 and 88 % respectively . The TDM is a practical , cost-efficient approach to reducing non-response bias in postal surveys and as such has an important role in epidemiological research which involves healthy participants Objectives : To evaluate the use of a self-administered quantitative food frequency question naire ( QFFQ ) in a national dietary survey concerning ( a ) response rates with different distribution methods and reward ; ( b ) degree of underreporting of energy intake ; ( c ) reproducibility of the QFFQ ; and ( d ) seasonal variation on reported intake . Design and subjects : A pilot study was performed in 1992 to test response rates to the QFFQ with three different distribution methods , with and without reward , in a r and om sample of 1200 adults aged 16–79 y. In another study , the QFFQ was distributed to a nation-wide , representative r and om sample of 5008 adults aged 16–79 y during June , September , November 1993 and March 1994 . Reproducibility was evaluated among 90 responders to the survey who answered another QFFQ six weeks later . Results : The distribution method combining postal distribution and collecting the QFFQ by interviewer as well as an offer to participate in a lottery , gave the highest response rate ( 72 % ) . The possibility to get a reward increased the response rate by 9 , 14 and 57 % , respectively , depending on the distribution method used . The mean daily energy intake and the percentage of subjects cl aim ing to have unlikely low energy intake did not differ significantly between the different ways of distribution . In the main survey the mean ratio between energy intake and estimated basal metabolic rate was 1.58 among men and 1.47 among women , and 37 % of men and 45 % of women had a ratio below 1.35 . Spearman rank correlations between the two QFFQ ranged from 0.48 ( edible fats ) to 0.91 ( coffee ) with a median coefficient of 0.70 . For nutrients correlations ranged from 0.55 ( carbohydrate E% ) to 0.81 ( alcohol ) , with a median coefficient of 0.72 . The season of question naire administration was of minor importance for the reported intake of the main foods and nutrients . Conclusions : The QFFQ- method is suitable for use in a Norwegian nutritional surveillance system . Sponsorship : National Nutrition Council , Ministry for Agriculture , Ministry for Health and Social Affairs and Norwegian Research Council The purpose was to examine the effectiveness of a modest monetary incentive ( $ 1 ) and none in increasing the response rate of a mail survey to 600 nurse practitioners . The response rate in the incentive group was 81 % and 66 % in the control group , significant by chi-square test . The most cost effective survey technique for increasing the response rate of nurse practitioners was to code the envelopes and eliminate the monetary incentive High response rates from physicians play an important role in obtaining valid data on practice patterns . We wanted to know whether two question naires ( one on hernia surgery and one on perioperative pain management ) should better be sent out in one letter or two separate letters . We r and omized 2,393 surgeons who received the two question naires either in one letter or by separate mail , in two letters , at a time interval of 4 weeks . The response rate for the separate mailout was not significantly higher when compared to the joint mailout . The differences were 3.3 % ( 95%-CI -0,4 % to 7.1 % ) and 2.2 % ( 95%-CI -1,4 % to 5.9 % ) for the two surveys . Due mainly to higher postage costs , the costs per response were doubled in the separate mailout group ( 5.85 Euro versus 2.93 Euro ) . Sending out two surveys separately seems to have only little effect on the response rates Objectives —To determine the effect of different methods of administering a diary to collect information from parents on near miss and minor injuries on responses , completeness and accuracy , the number of incidents reported , the effect of a financial incentive on response , and the cost of administering each method . Setting —The study was set within the context of a cluster r and omised controlled trial of injury prevention in 36 practice s in Nottingham . Methods —The study population comprised the 1594 parents who responded to the baseline question naire . Parents were allocated systematic ally to one of four groups : postal administration , with and without financial incentive , telephone administration , with and without financial incentive ( 102 in each group ) . A clinic visit method with and without financial incentive ( 50 in each group ) was also used . Results —A significant trend was found , with decreasing response rates with increasing degree of contact with the parent , such that administering the diary in the clinic had the lowest response ( χ2 for trend = 5.54 , 1 df , p = 0.02 ) . Offering a financial incentive increased responses from 47 % to 59 % ( χ2=5.78 , 1 df , p = 0.016 ) . The most complete recording was found in the diaries h and ed out at clinic visits . Importantly , parents were accurate in their recording of near miss and minor injuries , suggesting they understood the differences between the two types of incident . Postal methods were the least expensive method of administering the diary in terms of average cost per returned diary . Using a financial incentive result ed in a lower cost per returned diary for telephone and clinic visit methods . Conclusions —Parents can accurately and reliably complete diaries recording near miss and minor injuries occurring to their preschool children . More work is needed to investigate methods of increasing response . Postal diaries achieve the highest response but have the least complete recording of data . Diaries administered through child health clinics were most complete but achieved the lowest response . The administration method chosen in future work should be influenced both by the response and completeness of recording that is required by the research Measures of association in prospect i ve studies can be distorted by incomplete follow-up . Various mailing strategies were used to contact 12,233 cohort members of the Health Professionals Follow-up Study who had not responded to three successive bulk-rate mailings . Response rates were highest , 79.5 % overall , from participants who were sent a certified mailing in phase 1 ( 63.2 % ) , followed by a repeat certified mailing to nonrespondents ( 44.3 % ) . Although altering the physical appearance of the envelope and using other postal rates were tested , certified mail was the most effective approach for reaching study members who were nonrespondents to a mailed question naire Mailed surveys are a popular means of obtaining data on large population s. In July 1999 a mail survey was conducted among 3000 r and omly selected members of the American Society of Hematology to assess their approach to diagnosis and treatment of polycythemia vera . Because the research ers and the study population are members of the same professional organization with a vested interest in the results , we anticipated that the advantages of return stamped postage seen in previous studies would be less significant . The response rate for stamped return envelopes was 38 % versus 32 % for business reply envelopes . This statistically significant difference ( P = .0005 ) of six percentage points is comparable to previous research . Excluding labor , the total cost per returned survey was $ 2.62 for business reply envelopes versus $ 1.82 for stamped return envelopes . We conclude that stamped return envelopes are a more effective and cost-efficient means of procuring data from physician specialists Abstract : We conducted a r and omised trial to determine the differential effectiveness of a telephone prompt by a medical research er compared with a nonmedical research assistant in improving response rates of general practitioners to a survey and to compare personnel costs . A national r and om sample of Australian general practitioners was allocated r and omly to two intervention groups . In advance of a self – administered question naire , Group A ( n = 184 ) received a telephone prompt by a medical research er and Group B ( n = 189 ) a prompt by an experienced nonmedical research assistant . Other aspects of survey administration were identical for both groups . The five – month cumulative response rate obtained by the medical research er ( 81 per cent ) was not significantly different from that of 72 per cent obtained by the research assistant ( X2= 3.3 , 1 df , P = 0.07 ) . For Group A , 279 telephone calls , consuming 23 hours 15 minutes , were made . Group B required more calls ( 384 ) and more time ( 32 hours ) . Using the relevant award pay scales , the estimated personnel costs for each group were $ 631 and $ 601 respectively . We conclude that an experienced nonmedical research assistant is as effective as a medical practitioner in administering telephone prompts to enhance survey response rates , although savings are not necessarily made It is cheap to process epidemiological data from optical mark read ( OMR ) question naires . Respondents should use a pencil to complete OMR question naires , but many will not unless these are supplied . Sending pencils and erasers is expensive . Does sending pencils and erasers increase the response rate as cost-effectively as sending reminders , or does this decrease the error rate and offset data checking costs ? We mailed 300 smokers and half were r and omised to receive pencils and erasers . The relative risk ( 95 % confidence intervals ) for the response rate for the pencil group relative to the non-pencil group was 0.77 ( 0.46 - 1.29 ) and for the error rate was 1.31 ( 0.78 - 2.21 ) . Sending pencils and erasers was not cost-effective in sensitivity analysis with any response rate or using the confidence intervals . Including pencils with mailed epidemiological question naires probably has no benefit and any plausible benefit does not offset the costs of sending pencils and erasers STUDY OBJECTIVE --The study aim ed to consider the impact of two different types of reminder on response rates and costs in a postal survey . DESIGN --The study was a cross sectional survey . A self-completion lifestyle question naire was used . Those who did not respond after the initial mailing were r and omly allocated to receive either a postcard or question naire as a first reminder . All outst and ing non-responders received a question naire as a second reminder . SUBJECTS -- A representative sample of 698 adults aged 16 - 70 was used , drawn from a family health services authority register . MAIN RESULTS --Postcard reminders were as effective as question naire reminders in increasing response whether one or two reminders are sent . The costs per response were calculated . Two question naires as reminders were found to be 1.7 times more expensive than a postcard plus question naire . Including the initial mailing , the cost per response using all question naires was 1.3 times the cost when a postcard was used for the first reminder . CONCLUSIONS --To increase the response to a postal survey effectively and economically , two reminders should be sent -- first a postcard and then a question naire The authors r and omly selected 400 physicians from a population of 1,545 practicing physicians providing follow-up care to patients who received bone marrow or blood stem cell transplants at the Fred Hutchinson Cancer Research Center to determine interest in receiving Internet-based transplant information . In a two-factor completely r and omized factorial design , the 400 physicians were assigned to receive mailed surveys with either no compensation or a $ 5 check and either no follow-up call or a follow-up call 3 weeks after mailing . Overall , 51.5 % of the physicians returned the mailed surveys . Comparison of logit models showed that inclusion of a $ 5 check in the mailer significantly ( p = .016 ) increased the probability of returning the surveys ( 57.5 % vs. 45.5 % ) . In contrast , the telephone follow-up had no overall effect . The authors concluded a modest financial reward can significantly improve physician response rates to research surveys but a telephone follow-up may be inefficient and even ineffective It is becoming increasingly difficult to obtain high response rates in physicians ' mail surveys . In 1983 - 84 , we tested the effectiveness of two techniques among 604 Quebec physicians who had not responded to an initial letter . A h and written thank you note at the bottom of the letter accompanying the question naire and a more personalized mailout package increased response rates by 40.7 per cent and 53.1 per cent , respectively , compared to control groups We assessed the effect of a $ 1 incentive on response to a two-page question naire which was sent to 8356 female cosmetologists between 22 and 36 years old . The study population was r and omly assigned to one of three groups in which a $ 1 incentive was enclosed with either the first or second mailing , or with none of the mailings . Ten percent of question naires were returned by the postal service because of an incorrect address or death of the addressee and were omitted from response calculations . Of the remaining question naires , 79 % were completed and returned after up to three mailings . The cumulative response was highest among cosmetologists who received a $ 1 incentive with the first mailing , ( 81 % ; 95 % confidence interval ( CI ) , 80 to 82 ) , intermediate among those who received $ 1 with the second mailing ( 78 % , 95 % CI , 77 to 79 ) , and lowest among cosmetologists who received no incentive ( 74 % ; 95 % CI , 70 to 78 ) . Characteristics of cosmetologists who responded after having received a " 41 incentive were similar to those who responded without having received an incentive . The higher costs per response incurred by the use of an incentive must be weighed against the benefit of higher response Recruiting participants for large prevention trials is time consuming and costly . In order to test various recruitment techniques , we conducted two studies of response rates to recruitment mailings for the Women 's Health Trial . The potential participants , 50- to 79-year-old women , were requested to return an enclosed postcard to learn more about the trial . In the first study , we sent at r and om either a short or a long message to a group of University of Miami personnel ( N = 862 ) and a Dade County cohort ( N = 2964 ) . More university women responded to the short message than to the long message ( 22.4 % vs 16.4 % , p = 0.024 ) . Similarly , more of the Dade County cohort replied to the short message than to the long one ( 12.1 % vs 9.6 % , p = 0.027 ) . The long message listed details of the intervention ( e.g. , modifying recipes ) that some women may have used to decide they were not interested in participating . In the second study , we examined response rates to two different ways of addressing the mailing , i.e. , h and written envelopes and machine-printed labels ; we also evaluated three methods for delivering the short message : ( 1 ) formal invitation , ( 2 ) business letter with an inside name and address of the recipient , and ( 3 ) business letter without the recipient 's name and address . Response rates were similar between the methods of addressing envelopes and among the three vehicles for the message , suggesting that the least costly method of mailing should be used The Consumer Satisfaction Question naire ( CSQ ) was developed by Larsen , Atkisson , Hargreaves , and Nguyen ( 1979 ) and has been mentioned as a possible “ st and ard scale ” for the evaluation of consumer satisfaction with mental health treatment because of its unidimensionality , reliability , validity and ease of use . A mail survey of ex-clients who had terminated treatment during the preceding year from one of six offices of a regional mental health center in the Rocky Mountain area strongly cross-vali date d these characteristics as well as other results from the consumer satisfaction literature . In addition , based upon evidence from marketing research , a r and omly selected half of the ex-clients surveyed was offered a token inducement of two cents for returning the question naire while the other half was not . A significantly greater proportion of ex-clients who received the token inducement returned their question naires than did those who had not . This approach appears to be promising and further research with it is indicated BACKGROUND The study objective is to evaluate the effect of monetary incentives on response rates of adolescents to a smoking-related survey as the first step toward participation in an intervention trial . METHODS A sample of 4,200 adolescent members of a managed care organization were r and omized to one of four incentive groups : a $ 2 cash group , a $ 15 cash group , a $ 200 prize drawing group , or a no-incentive group . We compared group-specific response rates and willingness to be contacted about future study activities , as well as costs . RESULTS Incentives increased survey response rates ( 55 % response without incentive vs. a 69 % response with incentive ) , with response of 74 % in the $ 15 cash group , 69 % in the token group , and 63 % with a prize incentive . Incentives did not adversely affect willingness of adolescents to be contacted about a smoking intervention , ( 65 % willing with incentives vs. 60 % without , P = 0.03 ) . In terms of cost per additional survey completed , token and prize groups were marginally more expensive than the no-incentive group ( $ 0.40 and $ 1.42 , respectively ) while the large cash incentive was substantially more costly ( $ 11.37 ) . CONCLUSIONS Monetary incentives improve response rates to a mailed survey , without adverse impact on willingness to further participate in intervention activities . However , a variety of issues must be considered when using incentives for recruitment to intervention studies Previous experimental research in other topic areas has shown that the choice of response alternatives can influence respondents ' reporting of the frequency of vaguely defined events and that the set of response alternatives is treated as information in the interpretation of the question . The aim of this study was to examine whether such affects would occur in the context of respondents reporting of health-related events using high and medium frequency closed format response categories , which might be used interchangeably by research ers . The study consisted of a postal survey of n = 518 patients aged ≥≥18 years r and omly selected from the patient list of a diabetes centre and who were equally and r and omly allocated to one of three conditions ( Condition A : high frequency response alternatives/horizontal orientation ; condition B : medium frequency response alternatives/horizontal orientations ; condition C : high frequency response alternatives/vertical orientation ) . Testing for the effect of response alternatives for the combined responses of five vaguely defined questions between conditions A and B was χ2 = 5.5 , p = 0.019 , for the difference in proportions , indicating that overall , those respondents presented with response alternatives discriminating at medium frequency , reported significantly fewer target events than those presented with high frequency response alternatives . Testing for the effect of orientation of the combined question responses between conditions A and C , differences in proportions between conditions , did not reach statistical significance ( p > 0.05 ) . Findings from this and previous studies indicate that response alternatives provide information on the interpretation of vaguely defined question naire items and that their choice should not be left to intuition alone when design ing question naire items The present study compared the performance of a multidimensional patient satisfaction question naire according to the timing of question naire administration . Comparisons were made in terms of : ( a ) the completeness and representativeness of the data set ( number of missing question naires , number missing item responses , respondents ' representativeness to the target population ) ; ( b ) the question naire acceptability to respondents ( time and difficulty to complete ) ; ( c ) the question naire reliability ; and ( d ) variability of scores . One hundred and ten consecutive breast cancer patients hospitalised for surgery were r and omised between being sent the comprehensive assessment of satisfaction with care ( CASC ) at 2 weeks ( T(2W ) ) or at 3 months ( T(3 M ) ) after hospital discharge . The time to complete the CASC was shorter at T(3 M ) than at T(2W ) and the mean percentage of item omission was lower at T(3 M ) ( 1.68 ) than at T(2W ) ( 3.82 ) . However , the response rate was much higher at T(2W ) ( 87 % ) than at T(3 M ) ( 66 % ) , making item omission non-significant . At both times of question naire administration sample s were equally biased towards patients having undergone a less invasive surgery . Moreover , the multi-item scales of the CASC demonstrated adequate internal consistency coefficients , except the general satisfaction scale at T(3 M ) , and fairly symmetrical distribution of scores . Response rate should be considered in priority . This criteria favoured an administration of the CASC shortly after discharge . Besides in a cancer patient population care experience and perception may vary in a 6 weeks time lapse . The timing of assessment needs to be clearly specified in cancer patients satisfaction survey This study used a r and omised controlled trial to evaluate the effectiveness of telephone prompts to increase the response rate of gynaecologists to a survey . A nine-page question naire about management of women with abnormal Pap smears was mailed to Fellows of the Royal Australian College of Obstetricians and Gynaecologists . A r and om sample was contacted in advance by telephone , and nonrespondents received a telephone reminder 14 days after the initial mail-out . The control group was mailed question naires and a reminder letter conventionally . On Day 25 , nonresponders in both groups were mailed a second question naire . Of the intervention group , 84 per cent responded to the survey compared to 69 per cent of the control group ( P = 0.005 ) . A telephone call in anticipation of a mailed question naire is highly recommended This two-part method ologic research was design ed to evaluate the effects of a financial incentive on question naire response rate and response bias for general dentists surveyed by mail . Subjects were 517 clinicians r and omly selected from a two-state population of practitioners insured by a single mal practice liability carrier . Subjects received a check for either $ 5 or $ 10 in the original mailing . In Study 1 , a single mailing and postcard follow-up result ed in a 57.8 percent ( 111/192 ) response rate . In Study 2 , employing Dillman 's Total Design Method , a 69.6 percent ( 208/299 ) response was obtained after a third mailing . Analysis of response rate by incentive level in each study revealed no significant differences . In contrast , early responders ( first mailing and follow-up postcard ) differed from late responders ( second and third mailings ) on age ( 41.4 vs 37.0 years ; T = 2.17 ; P = .032 ) , non-Caucasians ( 27.7 % vs 63.9 % ; chi 2 = 17.3 ; df = 4 ; P < .002 ) , females ( 13.9 % vs 27.8 % ; chi 2 = 3.9 ; df = 1 ; P < .05 ) , foreign-trained ( 7.0 % vs 19.4 % ; chi 2 = 16.5 ; df = 2 ; P < .001 ) , and dissatisfaction with practice ( 31 % vs 51 % ; chi 2 = 7.8 ; df = 4 ; P = .10 ) . Thus , the magnitude of the financial incentive in this experiment had no differential effect on response rate . But differences in responses from late responders ( proxies for nonresponders ) on demographic characteristics and key study variables suggest the persistence of response bias despite an acceptable response rate . Future dental health survey research should employ tests for response bias on both sets of variables Three controlled experiments tested the efficacy of 1 ) a postcard or telephone prompt , 2 ) a lottery , 3 ) monetary incentives , and 4 ) question naire length to recruit adult survey respondents to a r and om sample of residences in San Diego , California , during 1986 - 1988 . In experiment 1 , the group r and omly assigned to receive a telephone call prenotification plus the lottery incentive responded 26 - 66 % more frequently than did controls ( p = 0.02 ) after a single mailing . The postcard plus lottery was 17 - 54 % more effective than no intervention with controls ( p = 0.05 ) . A second mailing of the survey weakened these effects . In experiment 2 , the group r and omly assigned to receive a two-page survey with the lottery announcement responded 69 % more frequently after one mailing ( p = 0.03 ) and 53 % more frequently after a second mailing ( p = 0.04 ) than the group that received an eight-page survey without the lottery incentive . The shorter form alone or the lottery alone did not increase response rates significantly relative to the long form without a lottery . In experiment 3 , a monetary incentive of $ 5.00 contingent on response to the second mailing of the survey increased the rate of response from initial " nonresponders " by 100 % relative to control who received no incentive ( p = 0.03 ) and 75 % over those who received $ 1.00 not contingent on response ( p = 0.04 ) . Little sampling bias and no reactivity was attributable to the recruitment procedures The authors studied how the introduction of several modifications to a basic food frequency question naire can influence the results of dietary surveys . Modifications covered eight combinations based on three levels : increasing versus decreasing order of frequency categories ; question naires without versus with questions about portion sizes , and question naires without versus with extra non-dietary questions . The sample included 6783 women between the ages of 40 and 70 years who took part in mammography screening . The women were r and omly assigned to one of the eight study groups . All of the women in each group received one of the eight differently modified question naires . The forms extended in length by extra non-dietary questions and portion size categories result ed in a 20 % higher total non-response compared to the shorter basic form . Partial non-response was significantly lower for all four question naire types that included portion sizes . When portion sizes were included in the question naire , the reported mean frequency of consumption was significantly reduced for fat ( -10 times per month ) , milk ( -6 ) , bread ( -5 ) , vegetables ( -2 ) and fish ( -0.4 ) . The decreasing order of responses to the frequency categories was associated with a statistically significant increase in the frequency responses for bread ( 2.6 times per month ) , vegetables ( 2 ) and fish ( 0.6 ) . These data provide evidence that the design and extension of food frequency question naires influence the results of dietary studies OBJECTIVES This study assessed efforts to increase response rates to a mailed physician survey and examined whether , as a result , nonresponse bias was reduced . METHODS R and omly selected physicians and geneticists were mailed a question naire concerning genetics knowledge and attitudes . In the final but not the pilot survey , a $ 25 incentive and intensive follow-up were used to increase the response rate . RESULTS The response rate from physicians in the final survey was 64.8 % ( n = 1140 ) , compared with 19.6 % in the pilot test ( n = 69 ) . Sample representatives in sociodemographic and practice characteristics was improved by follow-up . Respondents recruited with more difficulty did not differ on the principal outcome variable , genetics knowledge , except on one subscore . Pilot study and final survey respondents did not differ in knowledge . CONCLUSIONS Although the effect of increased response rates on the principal outcome variable in this study was minimal , this may not be the case for other studies . Every effort should be made to attain as high a response rate as is practical and to establish that respondents are representative of the population being sample In Engl and 600 people were r and omly selected from the electoral registers in Solihull in the West Midl and s for a study to determine whether the inclusion of a question about sexual health influenced the response rate to a postal survey design ed to monitor lifestyle factors ( e.g. diet exercise alcohol and smoking ) . 300 of the 600 question naires included the sexual health question : If you have had a sexual partner in the past 12 months please indicate below the type of contraception you or your partner regularly use ( options : none rhythm the pill condom Femidom coil cap withdrawal sexual sterilization post menopause other and does nt apply ) . The response rates for the 2 question naires were not statistically different ( 53.3 % for sexual health question naire vs. 51 % for other question naire ; p = 0.567 ) . The response rates for the follow-up of a second question naire were almost identical for both groups ( 70 % vs. 69.7 % ) . Only 3 % of people responding to the second question naire with the sexual health question did not respond to the sexual health question . The groups of people responding to both question naire types were similar in age sex residency and ethnicity . The results suggest a possible upcoming shift in the UK towards more cultural acceptance of sexual topics . Future studies should ask more detailed questions on sexual health to test this acceptance The authors examined differences in rate of response , data quality , and cost between mail approaches and in-person interview in the collection of data on sexual history and personal behaviors . A sample of women from a midwestern United States university ( n = 342 ) was identified from health service medical records as having been seen for a sexually transmitted disease ( cases ) or a contraceptive visit ( controls ) during the latter half of 1985 . The women were r and omly assigned to one of three data collection strategies . A total of 268 subjects ( 78 % ) participated . Results indicated no differences in validity by method of data collection or by case-control status but there were significant differences in completeness , cost , and response rates . In-person interviews result ed in more complete data than mail approaches , although all instruments had low proportions of missing data ( 0.001 - 0.006 ) . Response rate differences were not found when data collection method ologies were compared ( 75 - 82 % ) but were found in case-control analyses . Cases were consistently less likely to participate and significantly less likely to respond by mail ( p less than 0.05 ) . The cost of the in-person interview was approximately four times that of the mail survey for the data collection . Implication s of the case-control response rate difference suggest that mail method ologies , although low in cost , may introduce sampling bias in studies of sexually transmitted diseases Postal question naires are frequently used in research . One way of improving response rates is to use lotteries , although the evidence for their effectiveness is equivocal.1 - 4 An alternative , or complementary , approach to using lotteries is to make direct payments to survey responders . Few trials have evaluated direct payment compared with lotteries.3 Question naires about menopause services in the North West of Engl and were sent to a r and om sample of 1000 women aged 40 to 65 during September to November 1997 . The question naires included questions about use of hormone replacement therapy ( HRT ) and women 's demographic characteristics . The sample of women were r and omised in a 2 × 2 factorial trial to estimate the effectiveness of the two forms of incentive and their potential interaction within a single study . Unequal r and omisation of 3 to 1 favouring no direct payment was used to minimise research costs , which led We conducted a pilot study to determine the most efficient mailing strategy for a postal question naire study among nurses in Ontario , Canada . Five mailing strategies involving types of stamps on the return envelopes were considered : no stamp , business-reply stamp , metered stamp , small regular stamp , and large commemorative stamp . We found that paper stamps , especially large commemorative stamps , on return envelopes increased the response rate and reduced the response time , as compared with other mailing strategies . Business-reply stamps had the lowest cost per response received and a low total cost Mailed question naires are an economical method of data collection for epidemiologic studies , but response tends to be lower than for telephone or personal interviews . As part of a follow-up study of volunteers who provided a brief health history and blood sample for a blood specimen bank in 1989 , the authors conducted a controlled trial of the effect of length , incentives , and follow-up techniques on response to a mailed question naire . Interventions tested included variations on length of the question naire , effect of a monetary incentive , and effect of a postcard reminder versus a letter accompanied by a second question naire . Response was similar for the short ( 16-item , 4-page ) and long ( 76-item , 16-page ) question naire groups . The non-monetary [ corrected ] incentive did not improve the frequency of response . The second mailing of a question naire was significantly better than a postcard reminder in improving responses ( 23 % vs. 10 % ) . It is important to systematic ally test marketing principles to determine which techniques are effective in increasing response to mailed question naires for epidemiologic studies In the general population , the use of stamps rather than business reply postage significantly improves response rates in mail surveys . Among physicians , however , a smaller effect might be anticipated due to their greater sophistication . An experiment was conducted to test the hypothesis that stamps would improve response rates and lower costs in a physician survey that included intensive follow up . In 1989 , 380 physicians who reported providing primary care were surveyed . The protocol included two mailings , a postcard reminder , and two telephone reminders . Physicians were r and omly assigned to receive a return envelope with a first-class stamp or an envelope that had been preprinted " business reply mail " in the first and second mailings . Response rates , calculated as completed surveys divided by eligible physicians , were 83.8 and 72.1 % for stamps and business reply respectively , a difference of 11.7 percentage points ( p < 0.01 ) . Moreover , the total cost per completed survey was $ 11.18 for the physicians receiving stamps and $ 14.25 for the physicians receiving business reply . As in mail surveys of the general public , the use of first-class stamps on return envelopes both improves response rates and reduces cost in surveys of physicians Institutional review boards often require the consent of a patient 's doctor before a patient can be included in research studies . The process of obtaining consent can be long and costly , and excluding patients when consent can not be obtained could limit the generalisability of results . We examined strategies ( over which investigators might have control ) to increase the response rate of doctors asked to provide consent to contact their patients . We identified the doctors of patients with cancer who were being asked to participate in a population based case-control study . These doctors were r and omly assigned to one of eight treatments within two groups ( affiliation with teaching hospital or non-teaching hospital ) . The eight treatments were combinations of signatory of the request letter ( MD v PhD ) , letterhead ( university v cancer agency ) , and presence or absence of a h and written note thanking the doctor for The impact of a disease on health related quality of life is important but difficult to measure . If the instrument used for measuring this is too complicated some people may not answer some questions and others may not respond at all . Although incomplete data may introduce biases , make interpretation difficult , and reduce the generalisability of the results , 1 papers on selecting quality of life instruments have ignored response frequency.2 ( 2 , 3 ) We postulated that the brevity and simplicity of the EuroQol question naire ( six separate questions and a visual analogue scale ) would achieve a better response in stroke survivors than the SF-36 ( 34 separate questions ) and performed a r and omised controlled trial to test this hypothesis . We included all patients who had been entered by United Kingdom centres in the International Stroke Trial between 2 March 1993 and 31 May 1995 who were not known To determine whether academic physicians ' response rates to a mail survey depend on the envelope used to mail the survey , we r and omized 901 internists affiliated with a university department of medicine to receive a survey in either a university envelope or a Veterans Affairs envelope . The response rate among those receiving the Veterans Affairs envelope ( 41 % ) was 20 % higher than the response rate among those receiving the university envelope ( 34 % ) . We conclude that the packaging of a mail survey can influence the response rate The purpose of this study was to assess the impact of sponsorship of a mailed satisfaction survey on response patterns and patient satisfaction ratings , and to establish whether satisfaction ratings depend on the timing of response . The study was part of a patient satisfaction survey conducted in a medical group practice in Geneva , Switzerl and . All persons who had received an outpatient visit at the medical practice in the last week of September 1993 were assigned r and omly to receiving the survey package either on university letterhead or on the medical practice letterhead . Participation rates were 80.5 % and 80.4 % in the two groups , respectively . The sponsorship of the survey had no detectable impact on response speed or response completeness . Six out of seven satisfaction scores were higher in the " medical practice " group , but the differences were not statistically significant . As data collection progressed , the cumulative satisfaction rating decreased gradually . This association was statistically significant but moderate . Whether a satisfaction survey is sponsored by a university or a health care provider does not seem to affect survey results . However , low survey response rates may moderately bias satisfaction estimates toward higher values OBJECTIVE To test a possible day-of-the-week effect on doctors ' response rate to a postal question naire . DESIGN Dispatch of postal question naire r and omized to Thursday or Saturday . SETTING A nationwide survey on doctors ' attitudes . SUBJECTS 200 general practitioners and 260 practising specialists/consultants . MAIN OUTCOME MEASURES Response rate and Kaplan-Meier survival curve for no-response . RESULTS The probability of response was not influenced by receiving the question naire just before or just after a week-end . CONCLUSION Response rates in postal surveys sent to doctors can not be improved by their receiving the question naire just before a week-end Study sample Power calculations were used to determine the sample size . A 1300-patient sample would demonstrate a 10 % absolute difference ( 0.01 significance , 90 % power ) , and have an evens chance of identifying a 5 % difference at the 0.05 significance level . A total of 1,307 patients were eligible for inclusion in the study . A total of 654 patients were r and omly included in the intervention group , and 653 were r and omly allocated to the control group Dentists currently practising within the Central Sydney Area were surveyed ( n = 179 ) . A r and omized controlled trial was conducted to evaluate the effect of an advance telephone prompt ( intervention group ) compared with an advance letter prompt only ( control group ) in maximizing the response rate to a self-administered question naire . While the overall response rate was 83 per cent , the final response rate ( 89 per cent ) from dentists in the intervention group was significantly higher than that from dentists in the control group ( 78 per cent ) ( chi 2 = 4.14 , df = 1 , p = 0.04 ) . Advance telephone prompts are effective in maximizing the response rates from dentists and are recommended in future surveys of this professional group Patient surveys are commonly distributed at the end of a multicenter clinical trial . This Antiarrhythmics Versus Implantable Defibrillators ( AVID ) sub study prospect ively explored the relationship between methods used in distributing a survey and the quantity of responses received . AVID was a multicenter , r and omized trial comparing survival in arrhythmia patients treated with antiarrhythmic drugs versus implantable defibrillators . At study termination , a patient satisfaction survey was mailed to the 664 surviving participants . Questions included reasons for study participation , study benefits and problems and quality of care . Survey mailings were stratified by four factors in a 2x2x2x2 factorial design : delivery mode ( overnight vs. regular mail ) , certificate of appreciation , timing of administration ( " early " vs. " late " ) and cover letter signed by a physician versus coordinator . Patients were r and omly assigned to received one of 16 combinations of these four factors . Clinical characteristics and response rates were evaluated . Patients were more likely to return surveys delivered by overnight mail ( 75 % vs. 68 % , p=0.04 ) , with no certificate of appreciation enclosed ( 75 % vs. 68 % , p=0.05 ) and administered close to the time of study closeout ( 79 % vs. 72 % , p=0.085 ) . Compared to the 184 nonrespondents , the 456 ( 71 % ) respondents were older , Caucasian , lived with others , were high school graduates and less likely to have Medicare/Medicaid or HMO insurance ( p<0.03 ) . Physician recommendation was the most common reason cited for trial participation . Main benefits included increased knowledge of their medical condition and improved health . Reported problems included parking , transportation and excess clinic wait time . This r and omized study demonstrated that methods of patient survey distribution affect the survey return rate . Additional studies should explore mechanisms for maximizing return rates Alms : To identify whether the form of introduction to a study and knowledge of a substantial prize influence the response rate of general practitioners ( GPs ) to a postal survey The recruitment and retention of African Americans into cancer control studies presents a formidable task to the scientific and policy communities as well as patient and advocacy communities . The purpose of this investigation was to assess the role of a timed incentive schedule on response rates in a study of African American and white breast cancer survivors . A mailed quality -of-life survey battery was sent to 583 breast cancer survivors ( 50 % African American , 50 % white ) . Half of the participants received payment in advance , whereas the other half was promised payment . The overall response rate was 54 % ( n = 278 ) . The timing of incentives did not affect participation rates in either ethnic group . About 51 % of the respondents were from the payment-in-advance condition and 49 % were from the paid-on-completion condition . Therefore , we conclude that payment on completion may be the more cost-effective approach in studies with higher socioeconomic status patients , such as this sample of breast cancer survivors Postal surveys are a cost effective method of obtaining information from large numbers of geographically disparate medical professionals about their attributes , behaviours , attitudes and beliefs . The validity of the findings of such surveys is primarily dependent upon an adequate response rate and it is of concern that the rates are declining.1 Inclusion of a pen along with the question naire is often used to counter this trend . In theory , the availability of a pen would enable immediate completion of the question naire . The gift of a pen may also predispose the recipient to look upon the question naire more favourably increasing the likelihood of a response . However , the effectiveness of this strategy has not been established . Therefore as part of a national survey of consultant gynaecologists , we conducted a r and omised controlled trial , to determine if The context of the trial reported here was a two phase community based observational study to ascertain the prevalence of various chronic conditions . The first phase entailed a postal screening question naire ; the second involved clinical examinations of screen positives and a sample of screen negatives . To maximise compliance with the second phase , it was considered valuable to obtain subjects ’ telephone numbers from the initial question naire . However , there was concern that requesting this information might reduce the question naire response rate . Potential sensitivity to divulging this information is clear in a community setting where in the experience of ourselves and others the proportion of people who are ex-directory is around 25 % ( David Mouncey , personal communication ) . Previous r and omised controlled trials on optimising question naire response rates have focused on either financial incentives or the apparent mailing source . Although a number have investigated the impact of asking sensitive questions ( for example , about ethnic group 3 or explicit questions regarding cancer ) , the impact of requesting telephone numbers has not previously been investigated To assess whether changing the layout of the SF-12 affected item response rates , we tested two SF-12 formats in a quasi-r and omized trial of women aged > or=70 years in two general practice s in North Yorkshire . The modified version of the SF-12 ( ' York SF-12 ' ) converted the ' stem and leaf ' format of some questions to individual items . We assessed the effect of the two types of question naires on item response rates . The difference in overall response rates to the two question naires ( York SF-12 26.8 % ; SF-12 29.5 % ) was not statistically significant ( 95%CI -1.88 % to 7.22 % ) . However , the modified SF-12 had a statistically significantly lower item non-response rate of 8.5 % , compared with the 26.6 % of the SF-12 ( 95%CI 11.1%-25.1 % ) . Chronbach 's alpha reliability scores for the York SF-12 were also slightly better than for the older version . The York version of the SF-12 is an improvement on the original question naire . We recommend that the York SF-12 be used in preference to the SF-12 when surveying an older population STUDY OBJECTIVE --The purpose was to determine whether asking about ethnic origin and housing tenure in a postal survey affects the response rate . DESIGN --The study derived from a postal survey design ed to determine eligibility for a study of out patients . A two way factorial design was used to look at the two experimental factors , question naires being r and omly divided into four groups with or without questions about ethnic origin and housing tenure . PARTICIPANTS --10,000 people ( 1000 from each of 10 areas ) were systematic ally sample d from electoral registers , the areas being chosen to give a nationally representative sample . MAIN RESULTS --The response rate was 66 % irrespective of whether ethnic origin was asked about , but was 65 % and 67 % respectively to question naires with and without questions about housing tenure . CONCLUSIONS --Asking about ethnic origin did not affect the overall response to this survey although it is possible that the response from some ethnic minority groups was lower . Asking about housing tenure slightly , but significantly , decreased response Background .Mail surveys of physicians have been characterized by lower response rates than general population surveys , raising concerns about nonresponse bias . Although monetary incentives have routinely been used to improve survey response among physicians , questions remain regarding how much of an incentive is most cost-effective . The present study seeks to further examine the effects of incentive size on response rates to a national mail survey of physicians . Methods .This study used a r and om sample of 873 physicians practicing in the United States ; the response rate was 65 % ( n = 563 ) . Respondents were r and omly assigned to receive a $ 5 , $ 10 , or $ 20 cash incentive in the initial mailing . Except for the magnitude of the incentive , the procedures for each condition were identical , with each respondent receiving up to 3 follow-up mailings and 2 telephone calls . Results .Overall response rates ranged from 60.3 % for the $ 5 incentive category to 68.0 % for the $ 10 incentive category . Differences in overall response rates across the incentive categories , however , were not significant . Higher levels of incentives also did not significantly reduce the number of mail and /or telephone interventions required to reach the target response rate of 60.0 % . As expected , aggregate costs ( excluding labor ) were lowest for the $ 5 incentive group . Conclusions .Our findings suggest that changes in the magnitude of incentive do not automatically result in increases in survey response among physicians . Possible reasons for this lack of effect as well as alternatives to monetary incentives are addressed As part of a mailed health survey , we investigated the effect on the response rate of a request to explain refusal to participate . Subjects ( N = 1,240 ) were r and omized either to receive or not to receive , with the first mailing , a letter requesting an explanation of their decision not to fill out the question naire , if they chose that option . There was a slightly higher cumulative response during most of the study from subjects who had been sent the request , but little difference between the two study groups in the ultimate response rate [ 80 % from the intervention group vs 83 % from the control group ; response rate difference = -3 % ; 95 % confidence limits ( CL ) = -7 % , 1 % ] . Of 209 individuals who were sent the request and did not return the question naire , only 15 ( 7 % ) sent back an explanation . A request to explain a refusal to participate in a mail survey neither jeopardized the response rate nor enhanced it Effective strategies to maximize response rates to self-administered surveys of clinicians are crucial to minimize response bias . Offers of charitable donations have been assessed for their potential to promote participation of community sample s but not in the context of medical specialist sample s. We r and omized all Australian colorectal surgeons ( n = 219 ) to whom we mailed a survey about clinical practice guidelines to receive either a st and ard covering letter or one promising a donation to their peak professional organization upon our receipt of their completed survey . Contrary to expectations , surgeons advised that their participation would secure a donation to their college were significantly less likely to return their question naire ( 84.3 % , 95 % CI 76.0 - 90.5 % ) than those receiving a st and ard letter ( 93.7 % , 95 % CI 87.4 - 97.4 % ) . They also were more tardy in their response ( Hazard Ratio = 0.75 , 95 % CI 0.57 - 1.00 ) ( P = 0.047 ) . In this context , offering donations to surgeons was counterproductive in enhancing response rates The barrage of requests family physicians receive to complete mail surveys often results in physicians who are unwilling , or unable due to time constraints , to complete each survey they receive . Thus , to obtain an acceptable response rate , state-of-the-art mail survey techniques must be used . This article reports the results of the use of a modest($1 ) monetary incentive to increase a survey response rate . A r and om sample of 600 American Academy of Family Physicians members were mailed a survey of firearm safety counseling ; half received a $ 1 incentive whereas the remaining half served as a control group . The response rate in the incentive group was 63 % compared to 45 % in the control group [ X2 ( 1 , N = 251 ) = 16.0 , p < .0011 . Further , the use of the incentive appears to be more cost-effective than a thirdfollow-up ( postcard reminder ) mailing The aim of the present study was to compare the results obtained using two different methods of data collection about caries preventive services provided in general dental practice . A question naire was mailed to a r and om national sample of 479 dentists resident in Norway in January 1985 . The sample was divided into two groups by r and om allocation . All dentists , irrespective of group , were requested to give background information . One group , comprising 287 dentists ( GR ) , was asked to complete a separate form for every adult patient ( greater than or equal to 20 yr ) treated in the course of 1 day . The demographic characteristics and dental visiting habits of the patients , as well as the number of teeth present , caries lesions and preventive services rendered were recorded . The other group , 192 dentists ( GE ) , was requested to make general estimates of the time spent on caries prevention and the proportion of patients receiving various types of caries preventive services . The dentists were unaware of the method ologic aspect of the survey and everyone received one reminder in order to guarantee anonymity . The estimation method ( GE ) did not give the expected advantage over the registration method ( GR ) in response rate ( 51.7 % vs 46.2 % , P greater than 0.40 ) , and gave a gross overestimation of the frequency with which adult patients received different types of caries preventive procedures ( P less than 0.005 ) . Thus , even though the estimates of the proportion of total treatment time spent on caries prevention were comparable for the two methods , and the estimation approach is labor-saving , it can not be recommended for the collection of data on caries prevention in the dental office Although mailed surveys are an important component of epidemiological research , results from mailed surveys are often suspect because of poor response rates and the potential for nonresponse bias . Previous work has demonstrated that paying subjects to complete question naires increases response rates , but this work has not well addressed the impact of the timing of incentives on total cost , cost effectiveness , and response bias . We surveyed 400 university employees about health benefits . By r and om allocation , half received a check for $ 5 along with the mailed survey , and the other half received the promise of $ 5 on return of a completed survey . The response rates for both groups were about the same ( 64 and 59 % , respectively ) , but prepayment was less expensive in aggregate and less expensive per response . In addition , we found that subjects with lower salaries were more likely to respond when paid in advance . We conclude that prepayment may actually be less expensive and more cost effective than payment on completion , but that the timing of payment may influence the profile of respondents Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews R and omized trials were performed in Denmark and The Netherl and s to determine the effect of mailed reminders on the response rate in surveys among patients in general practice . In both countries , general practitioners h and ed out question naires to 200 adult patients who came to visit them . An intervention group of 100 patients received reminders at 3 weeks after the visit , whereas a control group of the remaining 100 patients did not receive reminders . The response rate was significantly higher in the intervention groups than in the control group in The Netherl and s ( 86 % versus 55 % , respectively ) but not in Denmark ( 87 % versus 81 % , respectively ) . Mailed reminders can improve the response rate in surveys related to a general practice , but they are not effective in all situations The effects of a number of controllable factors on the response rate of mothers to a postal question naire were assessed by a series of experiments . In one a factorial design was used to look at seven factors with a r and om sample of 1600 mothers . The main findings were that the responses to question naires of 8 , 16 or 24 pages were similar , but that rather more mothers replied when the question naires contained only factual questions than when they covered both facts and attitudes . Another experiment , based on a similar sample , compared the response rates when the question naires were sent out by a government organization or by the Institute for Social Studies in Medical Care , and found no difference . The final experiment looked at the effect of precoding the answers or asking respondents to tick boxes beside their replies and again found no difference in response rates . The overall response rate was 79 per cent , but this varied between 66 and 87 per cent in the ten r and omly selected study areas --a much greater variation than that found with any of the experimental factors This study 's goals were to ( a ) determine whether sending a survey by certified mail results in a higher response rate from physicians compared to sending by first-class mail and ( b ) evaluate the cost-effectiveness of this method . The study sample was 409 physicians who were nonrespondents to two previous mailings of a medical specialty society survey . Eligible physicians were design ated at r and om to receive afinal mailing either by U.S. Postal Service certified mail including a return-receipt postcard or by first-class mail . There was a higher response rate from the certified mail group compared with the first-class mail group ( 41.3 % versus 24.8 % ; relative risk = 1.66 , 95 % Confidence Interval 1.25 , 2.21 ) . A cost-effectiveness analysis showed that the cost per respondent was higher using certified mail versus first-class mail in the third mailing ( $ 2.77 versus $ 2.34 ) . Thus , use of certified mail is effective in increasing survey response but more costly To evaluate the cost-effectiveness of a lottery on physicians ’ responses to a mail survey , a r and omized controlled trial was conducted with a r and om sample of 1,000 members of the Quebec Federation of General Practitioners in 1997 . For the first mailing of this survey , each respondent was r and omly assigned to the control or experimental group , which was offered participation in a lottery upon return of the question naire . Response rate was 41.2 % in the experimental group and 34.8 % in the control group , a 6.4 % difference ( CI95 % : 0.6 % – 12.6 % ) . The additional cost of the lottery was about Can$500 , giving an incremental cost of Can$16 per question naire returned . In conclusion , a lottery result ed in a small but statistically significant increase in the response rate of physicians to a mail survey . This method may be a cost-effective option when applied to large surveys |
1,646 | 30,157,514 | RESULTS We found that 10 behavioral economics concepts with nine cognitive biases were addressed and investigated for clinician decision-making , and that the following five concepts , which were actively explored , had an impact in CDS applications : social norms , framing effect , status-quo bias , heuristics , and overconfidence bias .
CONCLUSIONS Our review revealed that the use of behavioral economics techniques is increasing in areas such as antibiotics prescribing and preventive care , and that additional tests of the concepts and heuristics described would be useful in other areas of CDS . | BACKGROUND Clinical decision support ( CDS ) systems can improve safety and facilitate evidence -based practice .
However , clinical decisions are often affected by the cognitive biases and heuristics of clinicians , which is increasing the interest in behavioral and cognitive science approaches in the medical field .
OBJECTIVES This review aim ed to identify decision biases that lead clinicians to exhibit irrational behaviors or responses , and to show how behavioral economics can be applied to interventions in order to promote and reveal the contributions of CDS to improving health care quality . | Summary Background Unnecessary antibiotic prescribing contributes to antimicrobial resistance . In this trial , we aim ed to reduce unnecessary prescriptions of antibiotics by general practitioners ( GPs ) in Engl and . Methods In this r and omised , 2 × 2 factorial trial , publicly available data bases were used to identify GP practice s whose prescribing rate for antibiotics was in the top 20 % for their National Health Service ( NHS ) Local Area Team . Eligible practice s were r and omly assigned ( 1:1 ) into two groups by computer-generated allocation sequence , stratified by NHS Local Area Team . Participants , but not investigators , were blinded to group assignment . On Sept 29 , 2014 , every GP in the feedback intervention group was sent a letter from Engl and 's Chief Medical Officer and a leaflet on antibiotics for use with patients . The letter stated that the practice was prescribing antibiotics at a higher rate than 80 % of practice s in its NHS Local Area Team . GPs in the control group received no communication . The sample was re-r and omised into two groups , and in December , 2014 , GP practice s were either sent patient-focused information that promoted reduced use of antibiotics or received no communication . The primary outcome measure was the rate of antibiotic items dispensed per 1000 weighted population , controlling for past prescribing . Analysis was by intention to treat . This trial is registered with the IS RCT N registry , number IS RCT N32349954 , and has been completed . Findings Between Sept 8 and Sept 26 , 2014 , we recruited and assigned 1581 GP practice s to feedback intervention ( n=791 ) or control ( n=790 ) groups . Letters were sent to 3227 GPs in the intervention group . Between October , 2014 , and March , 2015 , the rate of antibiotic items dispensed per 1000 population was 126·98 ( 95 % CI 125·68–128·27 ) in the feedback intervention group and 131·25 ( 130·33–132·16 ) in the control group , a difference of 4·27 ( 3·3 % ; incidence rate ratio [ IRR ] 0·967 [ 95 % CI 0·957–0·977 ] ; p<0·0001 ) , representing an estimated 73 406 fewer antibiotic items dispensed . In December , 2014 , GP practice s were re-assigned to patient-focused intervention ( n=777 ) or control ( n=804 ) groups . The patient-focused intervention did not significantly affect the primary outcome measure between December , 2014 , and March , 2015 ( antibiotic items dispensed per 1000 population : 135·00 [ 95 % CI 133·77–136·22 ] in the patient-focused intervention group and 133·98 [ 133·06–134·90 ] in the control group ; IRR for difference between groups 1·01 , 95 % CI 1·00–1·02 ; p=0·105 ) . Interpretation Social norm feedback from a high-profile messenger can substantially reduce antibiotic prescribing at low cost and at national scale ; this outcome makes it a worthwhile addition to antimicrobial stewardship programmes . Funding Public Health Engl and Although self-enhancement is linked to psychological benefits , it is also associated with personal and interpersonal liabilities ( e.g. , excessive risk taking , social exclusion ) . Hence , structuring social situations that prompt people to keep their self-enhancing beliefs in check can confer personal and interpersonal advantages . The authors examined whether accountability can serve this purpose . Accountability was defined as the expectation to explain , justify , and defend one 's self-evaluations ( grade s on an essay ) to another person ( " audience " ) . Experiment 1 showed that accountability curtails self-enhancement . Experiment 2 ruled out audience concreteness and status as explanations for this effect . Experiment 3 demonstrated that accountability-induced self-enhancement reduction is due to identifiability . Experiment 4 documented that identifiability decreases self-enhancement because of evaluation expectancy and an accompanying focus on one 's weaknesses Abstract Objective To determine whether a behavioral intervention delivered through a video game can improve the appropriateness of trauma triage decisions in the emergency department of non-trauma centers . Design R and omized clinical trial . Setting Online intervention in national sample of emergency medicine physicians who make triage decisions at US hospitals . Participants 368 emergency medicine physicians primarily working at non-trauma centers . A r and om sample ( n=200 ) of those with primary outcome data was reassessed at six months . Interventions Physicians were r and omized in a 1:1 ratio to one hour of exposure to an adventure video game ( Night Shift ) or apps based on traditional didactic education ( myATLS and Trauma Life Support MCQ Review ) , both on iPads . Night Shift was developed to recalibrate the process of using pattern recognition to recognize moderate-severe injuries ( representativeness heuristics ) through the use of stories to promote behavior change ( narrative engagement ) . Physicians were r and omized with a 2 × 2 factorial design to intervention ( game v traditional education apps ) and then to the experimental condition under which they completed the outcome assessment tool ( low v high cognitive load ) . Blinding could not be maintained after allocation but group assignment was masked during the analysis phase . Main outcome measures Outcomes of a virtual simulation that included 10 cases ; in four of these the patients had severe injuries . Participants completed the simulation within four weeks of their intervention . Decisions to admit , discharge , or transfer were measured . The proportion of patients under-triaged ( patients with severe injuries not transferred to a trauma center ) was calculated then ( primary outcome ) and again six months later , with a different set of cases ( primary outcome of follow-up study ) . The secondary outcome was effect of cognitive load on under-triage . Results 149 ( 81 % ) physicians in the game arm and 148 ( 80 % ) in the traditional education arm completed the trial . Of these , 64/100 ( 64 % ) and 58/100 ( 58 % ) , respectively , completed re assessment at six months . The mean age was 40 ( SD 8.9 ) , 283 ( 96 % ) were trained in emergency medicine , and 207 ( 70 % ) were ATLS ( advanced trauma life support ) certified . Physicians exposed to the game under-triaged fewer severely injured patients than those exposed to didactic education ( 316/596 ( 0.53 ) v 377/592 ( 0.64 ) , estimated difference 0.11 , 95 % confidence interval 0.05 to 0.16 ; P<0.001 ) . Cognitive load did not influence under-triage ( 161/308 ( 0.53 ) v 155/288 ( 0.54 ) in the game arm ; 197/300 ( 0.66 ) v 180/292 ( 0.62 ) in the traditional educational apps arm ; P=0.66 ) . At six months , physicians exposed to the game remained less likely to under-triage patients ( 146/256 ( 0.57 ) v 172/232 ( 0.74 ) , estimated difference 0.17 , 0.09 to 0.25 ; P<0.001 ) . No physician reported side effects . The sample might not reflect all emergency medicine physicians , and a small set of cases was used to assess performance . Conclusions Compared with apps based on traditional didactic education , exposure of physicians to a theoretically grounded video game improved triage decision making in a vali date d virtual simulation . Though the observed effect was large , the wide confidence intervals include the possibility of a small benefit , and the real world efficacy of this intervention remains uncertain . Trial registration clinical trials.gov ; NCT02857348 ( initial study ) /NCT03138304 ( follow-up ) Background The frequency of head computed tomography ( CT ) imaging for mild head trauma patients has raised safety and cost concerns . Vali date d clinical decision rules exist in the published literature and on-line sources to guide medical image ordering but are often not used by emergency department ( ED ) clinicians . Using simulation , we explored whether the presentation of a clinical decision rule ( i.e. Canadian CT Head Rule - CCHR ) , findings from mal practice cases related to clinicians not ordering CT imaging in mild head trauma cases , and estimated patient out-of-pocket cost might influence clinician brain CT ordering . Underst and ing what type and how information may influence clinical decision making in the ordering advanced medical imaging is important in shaping the optimal design and implementation of related clinical decision support systems . Methods Multi-center , double-blinded simulation-based r and omized controlled trial . Following st and ardized clinical vignette presentation , clinicians made an initial imaging decision for the patient . This was followed by additional information on decision support rules , mal practice outcome review , and patient cost ; each with opportunity to modify their initial order . The mal practice and cost information differed by assigned group to test the any temporal relationship . The simulation closed with a second vignette and an imaging decision . Results One hundred sixteen of the 167 participants ( 66.9 % ) initially ordered a brain CT scan . After CCHR presentation , the number of clinicians ordering a CT dropped to 76 ( 45.8 % ) , representing a 21.1 % reduction in CT ordering ( P = 0.002 ) . This reduction in CT ordering was maintained , in comparison to initial imaging orders , when presented with mal practice review information ( p = 0.002 ) and patient cost information ( p = 0.002 ) . About 57 % of clinicians changed their order during study , while 43 % never modified their imaging order . Conclusion This study suggests that ED clinician brain CT imaging decisions may be influenced by clinical decision support rules , patient out-of-pocket cost information and findings from mal practice case review .Trial registration NCT03449862 , February 27 , 2018 , Retrospectively registered Background Inappropriate antibiotic prescribing for nonbacterial infections leads to increases in the costs of care , antibiotic resistance among bacteria , and adverse drug events . Acute respiratory infections ( ARIs ) are the most common reason for inappropriate antibiotic use . Most prior efforts to decrease inappropriate antibiotic prescribing for ARIs ( e.g. , educational or informational interventions ) have relied on the implicit assumption that clinicians inappropriately prescribe antibiotics because they are unaware of guideline recommendations for ARIs . If lack of guideline awareness is not the reason for inappropriate prescribing , educational interventions may have limited impact on prescribing rates . Instead , interventions that apply social psychological and behavioral economic principles may be more effective in deterring inappropriate antibiotic prescribing for ARIs by well-informed clinicians . Methods / design The Application of Behavioral Economics to Improve the Treatment of Acute Respiratory Infections ( BEARI ) Trial is a multisite , cluster-r and omized controlled trial with practice as the unit of r and omization . The primary aim is to test the ability of three interventions based on behavioral economic principles to reduce the rate of inappropriate antibiotic prescribing for ARIs . We r and omized practice s in a 2 × 2 × 2 factorial design to receive up to three interventions for non-antibiotic-appropriate diagnoses : 1 ) Accountable Justifications : When prescribing an antibiotic for an ARI , clinicians are prompted to record an explicit justification that appears in the patient electronic health record ; 2 ) Suggested Alternatives : Through computerized clinical decision support , clinicians prescribing an antibiotic for an ARI receive a list of non-antibiotic treatment choices ( including prescription options ) prior to completing the antibiotic prescription ; and 3 ) Peer Comparison : Each provider ’s rate of inappropriate antibiotic prescribing relative to top-performing peers is reported back to the provider periodically by email . We enrolled 269 clinicians ( practicing attending physicians or advanced practice nurses ) in 49 participating clinic sites and collected baseline data . The primary outcome is the antibiotic prescribing rate for office visits with non-antibiotic-appropriate ARI diagnoses . Secondary outcomes will examine antibiotic prescribing more broadly . The 18-month intervention period will be followed by a one year follow-up period to measure persistence of effects after interventions cease . Discussion The ongoing BEARI Trial will evaluate the effectiveness of behavioral economic strategies in reducing inappropriate prescribing of antibiotics . Trials registration Clinical Trials.gov : PURPOSE We wanted to evaluate novel decision aids design ed to help patients trust and accept the controversial , evidence -based , US Preventive Services Task Force recommendations about prostate cancer screening ( from 2012 ) and mammography screening for women aged 40 to 49 years ( from 2009 ) . METHODS We created recorded vignettes of physician-patient discussion s about prostate cancer screening and mammography , accompanied by illustrative slides , based on principles derived from preceding qualitative work and behavioral science literature . We conducted a r and omized crossover study with repeated measures with 27 men aged 50 to 74 years and 35 women aged 40 to 49 years . All participants saw a video intervention and a more traditional , paper-based decision aid intervention in r and om order . At entry and after seeing each intervention , they were surveyed about screening intentions , perceptions of benefits and harm , and decisional conflict . RESULTS Changes in screening intentions were analyzed without regard to order of intervention after an initial analyses showed no evidence of an order effect . At baseline , 69 % of men and 86 % of women reported wanting screening , with 31 % and 6 % , respectively , unsure . Mean change on a 3-point , yes , unsure , no scale was −0.93 ( P = < .001 ) for men and −0.50 ( P = < .001 ) for women after seeing the video interventions vs 0.0 and −0.06 ( P = .75 ) after seeing the print interventions . At the study end , 33 % of men and 49 % of women wanted screening , and 11 % and 20 % , respectively , were unsure . CONCLUSIONS Our novel , persuasive video interventions significantly changed the screening intentions of substantial proportions of viewers . Our approach needs further testing but may provide a model for helping patients to consider and accept evidence -based , counterintuitive recommendations IMPORTANCE Antimicrobial stewardship programs have been effective for in patients , often through prescribing audit and feedback . However , most antimicrobial use occurs in out patients with acute respiratory tract infections ( ARTIs ) . OBJECTIVE To evaluate the effect of an antimicrobial stewardship intervention on antibiotic prescribing for pediatric out patients . DESIGN Cluster r and omized trial of outpatient antimicrobial stewardship comparing prescribing between intervention and control practice s using a common electronic health record . After excluding children with chronic medical conditions , antibiotic allergies , and prior antibiotic use , we estimated prescribing rates for targeted ARTIs st and ardized for age , sex , race , and insurance from 20 months before the intervention to 12 months afterward ( October 2008-June 2011 ) . SETTING AND PARTICIPANTS A network of 25 pediatric primary care practice s in Pennsylvania and New Jersey ; 18 practice s ( 162 clinicians ) participated . INTERVENTIONS One 1-hour on-site clinician education session ( June 2010 ) followed by 1 year of personalized , quarterly audit and feedback of prescribing for bacterial and viral ARTIs or usual practice . MAIN OUTCOMES AND MEASURES Rates of broad-spectrum ( off- guideline ) antibiotic prescribing for bacterial ARTIs and antibiotics for viral ARTIs for 1 year after the intervention . RESULTS Broad-spectrum antibiotic prescribing decreased from 26.8 % to 14.3 % ( absolute difference , 12.5 % ) among intervention practice s vs from 28.4 % to 22.6 % ( absolute difference , 5.8 % ) in controls ( difference of differences [ DOD ] , 6.7 % ; P = .01 for differences in trajectories ) . Off- guideline prescribing for children with pneumonia decreased from 15.7 % to 4.2 % among intervention practice s compared with 17.1 % to 16.3 % in controls ( DOD , 10.7 % ; P < .001 ) and for acute sinusitis from 38.9 % to 18.8 % in intervention practice s and from 40.0 % to 33.9 % in controls ( DOD , 14.0 % ; P = .12 ) . Off- guideline prescribing was uncommon at baseline and changed little for streptococcal pharyngitis ( intervention , from 4.4 % to 3.4 % ; control , from 5.6 % to 3.5 % ; DOD , -1.1 % ; P = .82 ) and for viral infections ( intervention , from 7.9 % to 7.7 % ; control , from 6.4 % to 4.5 % ; DOD , -1.7 % ; P = .93 ) . CONCLUSIONS AND RELEVANCE In this large pediatric primary care network , clinician education coupled with audit and feedback , compared with usual practice , improved adherence to prescribing guidelines for common bacterial ARTIs , and the intervention did not affect antibiotic prescribing for viral infections . Future studies should examine the drivers of these effects , as well as the generalizability , sustainability , and clinical outcomes of outpatient antimicrobial stewardship . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01806103 Background . Guidelines recommend that patient decision aids should provide quantitative information about probabilities of potential outcomes , but the impact of this information is unknown . Behavioral economics suggests that patients confused by quantitative information could benefit from a “ nudge ” towards one option . We conducted a pilot r and omized trial to estimate the effect sizes of presenting quantitative information and a nudge . Methods . Primary care patients ( n = 213 ) eligible for colorectal cancer screening viewed basic screening information and were r and omized to view ( a ) quantitative information ( quantitative module ) , ( b ) a nudge towards stool testing with the fecal immunochemical test ( FIT ) ( nudge module ) , ( c ) neither a nor b , or ( d ) both a and b. Outcome measures were perceived colorectal cancer risk , screening intent , preferred test , and decision conflict , measured before and after viewing the decision aid , and screening behavior at 6 months . Results . Patients viewing the quantitative module were more likely to be screened than those who did not ( P = 0.012 ) . Patients viewing the nudge module had a greater increase in perceived colorectal cancer risk than those who did not ( P = 0.041 ) . Those viewing the quantitative module had a smaller increase in perceived risk than those who did not ( P = 0.046 ) , and the effect was moderated by numeracy . Among patients with high numeracy who did not view the nudge module , those who viewed the quantitative module had a greater increase in intent to undergo FIT ( P = 0.028 ) than did those who did not . Limitations . The limitations of this study were the limited sample size and single healthcare system . Conclusions . Adding quantitative information to a decision aid increased uptake of colorectal cancer screening , while adding a nudge to undergo FIT did not increase uptake . Further research on quantitative information in decision aids is warranted IMPORTANCE Interventions based on behavioral science might reduce inappropriate antibiotic prescribing . OBJECTIVE To assess effects of behavioral interventions and rates of inappropriate ( not guideline -concordant ) antibiotic prescribing during ambulatory visits for acute respiratory tract infections . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized clinical trial conducted among 47 primary care practice s in Boston and Los Angeles . Participants were 248 enrolled clinicians r and omized to receive 0 , 1 , 2 , or 3 interventions for 18 months . All clinicians received education on antibiotic prescribing guidelines on enrollment . Interventions began between November 1 , 2011 , and October 1 , 2012 . Follow-up for the latest-starting sites ended on April 1 , 2014 . Adult patients with comorbidities and concomitant infections were excluded . INTERVENTIONS Three behavioral interventions , implemented alone or in combination : suggested alternatives presented electronic order sets suggesting nonantibiotic treatments ; accountable justification prompted clinicians to enter free-text justifications for prescribing antibiotics into patients ' electronic health records ; peer comparison sent emails to clinicians that compared their antibiotic prescribing rates with those of " top performers " ( those with the lowest inappropriate prescribing rates ) . MAIN OUTCOMES AND MEASURES Antibiotic prescribing rates for visits with antibiotic-inappropriate diagnoses ( nonspecific upper respiratory tract infections , acute bronchitis , and influenza ) from 18 months preintervention to 18 months afterward , adjusting each intervention 's effects for co-occurring interventions and preintervention trends , with r and om effects for practice s and clinicians . RESULTS There were 14,753 visits ( mean patient age , 47 years ; 69 % women ) for antibiotic-inappropriate acute respiratory tract infections during the baseline period and 16,959 visits ( mean patient age , 48 years ; 67 % women ) during the intervention period . Mean antibiotic prescribing rates decreased from 24.1 % at intervention start to 13.1 % at intervention month 18 ( absolute difference , -11.0 % ) for control practice s ; from 22.1 % to 6.1 % ( absolute difference , -16.0 % ) for suggested alternatives ( difference in differences , -5.0 % [ 95 % CI , -7.8 % to 0.1 % ] ; P = .66 for differences in trajectories ) ; from 23.2 % to 5.2 % ( absolute difference , -18.1 % ) for accountable justification ( difference in differences , -7.0 % [ 95 % CI , -9.1 % to -2.9 % ] ; P < .001 ) ; and from 19.9 % to 3.7 % ( absolute difference , -16.3 % ) for peer comparison ( difference in differences , -5.2 % [ 95 % CI , -6.9 % to -1.6 % ] ; P < .001 ) . There were no statistically significant interactions ( neither synergy nor interference ) between interventions . CONCLUSIONS AND RELEVANCE Among primary care practice s , the use of accountable justification and peer comparison as behavioral interventions result ed in lower rates of inappropriate antibiotic prescribing for acute respiratory tract infections . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01454947 Background The management of multiple sclerosis ( MS ) is rapidly changing by the introduction of new and more effective disease-modifying agents . The importance of risk stratification was confirmed by results on disease progression predicted by different risk score systems . Despite these advances , we know very little about medical decisions under uncertainty in the management of MS . The goal of this study is to i ) identify whether overconfidence , tolerance to risk/uncertainty , herding influence medical decisions , and ii ) to evaluate the frequency of therapeutic inertia ( defined as lack of treatment initiation or intensification in patients not at goals of care ) and its predisposing factors in the management of MS . Methods / Design This is a prospect i ve study comprising a combination of case-vignettes and surveys and experiments from Neuroeconomics/behavioral economics to identify cognitive distortions associated with medical decisions and therapeutic inertia . Participants include MS fellows and MS experts from across Spain . Each participant will receive an individual link using Qualtrics platform © that includes 20 case-vignettes , 3 surveys , and 4 behavioral experiments . The total time for completing the study is approximately 30–35 min . Case vignettes were selected to be representative of common clinical encounters in MS practice . Surveys and experiments include st and ardized test to measure overconfidence , aversion to risk and ambiguity , herding ( following colleague ’s suggestions even when not supported by the evidence ) , physicians ’ reactions to uncertainty , and questions from the Socio-Economic Panel Study ( SOEP ) related to risk preferences in different domains . By applying three different MS score criteria ( modified Rio , EMA , Prosperini ’s scheme ) we take into account physicians ’ differences in escalating therapy when evaluating medical decisions across case-vignettes . Conclusions The present study applies an innovative approach by combining tools to assess medical decisions with experiments from Neuroeconomics that applies to common scenarios in MS care . Our results will help advance the field by providing a better underst and ing on the influence of cognitive factors ( e.g. , overconfidence , aversion to risk and uncertainty , herding ) on medical decisions and therapeutic inertia in the management of MS which could lead to better outcomes OBJECTIVE : To assess the effects of electronic health record – based clinical decision support ( CDS ) and physician performance feedback on adherence to guidelines for acute otitis media ( AOM ) and otitis media with effusion ( OME ) . METHODS : We conducted a factorial- design cluster r and omized trial with primary care practice s ( n = 24 ) as the unit of r and omization and visits as the unit of analysis . Between December 2007 and September 2010 , data were collected from 139 305 otitis media visits made by 55 779 children aged 2 months to 12 years . When activated , the CDS system provided guideline -based recommendations individualized to the patient ’s history and presentation . Monthly physician feedback reported adherence to guideline -based care , changes over time , and comparisons to others in the practice and network . RESULTS : Comprehensive care ( all recommended guidelines were adhered to ) was accomplished for 15 % of AOM and 5 % of OME visits during the baseline period . The increase from baseline to intervention periods in adherence to guidelines was larger for CDS compared with non-CDS visits for comprehensive care , pain treatment , adequate diagnostic evaluation for OME , and amoxicillin as first-line therapy for AOM . Although performance feedback was associated with improved antibiotic prescribing for AOM and pain treatment , the joint effects of CDS and feedback on guideline adherence were not additive . There was marked variation in use of the CDS system , ranging from 5 % to 45 % visits across practice s. CONCLUSIONS : Clinical decision support and performance feedback are both effective strategies for improving adherence to otitis media guidelines . However , combining the 2 interventions is no better than either delivered alone CONTEXT Performance feedback and benchmarking , common tools for health care improvement , are rarely studied in r and omized trials . Achievable Benchmarks of Care ( ABCs ) are st and ards of excellence attained by top performers in a peer group and are easily and reproducibly calculated from existing performance data . OBJECTIVE To evaluate the effectiveness of using achievable benchmarks to enhance typical physician performance feedback and improve care . DESIGN Group-r and omized controlled trial conducted in December 1996 , with follow-up through 1998 . SETTING AND PARTICIPANTS Seventy community physicians and 2978 fee-for-service Medicare patients with diabetes mellitus who were part of the Ambulatory Care Quality Improvement Project in Alabama . INTERVENTION Physicians were r and omly assigned to receive a multimodal improvement intervention , including chart review and physician-specific feedback ( comparison group ; n = 35 ) or an identical intervention plus achievable benchmark feedback ( experimental group ; n = 35 ) . MAIN OUTCOME MEASURE Preintervention ( 1994 - 1995 ) to postintervention ( 1997 - 1998 ) changes in the proportion of patients receiving influenza vaccination ; foot examination ; and each of 3 blood tests measuring glucose control , cholesterol level , and triglyceride level , compared between the 2 groups . RESULTS The proportion of patients who received influenza vaccine improved from 40 % to 58 % in the experimental group ( P<.001 ) vs from 40 % to 46 % in the comparison group ( P = .02 ) . Odds ratios ( ORs ) for patients of achievable benchmark physicians vs comparison physicians who received appropriate care after the intervention , adjusted for preintervention care and nesting of patients within physicians , were 1.57 ( 95 % confidence interval [ CI ] , 1.26 - 1.96 ) for influenza vaccination , 1.33 ( 95 % CI , 1.05 - 1.69 ) for foot examination , and 1.33 ( 95 % CI , 1.04 - 1.69 ) for long-term glucose control measurement . For serum cholesterol and triglycerides , the achievable benchmark effect was statistically significant only after additional adjustment for physician characteristics ( OR , 1.40 [ 95 % CI , 1.08 - 1.82 ] and OR , 1.40 [ 95 % CI , 1.09 - 1.79 ] , respectively ) . CONCLUSION Use of achievable benchmarks significantly enhances the effectiveness of physician performance feedback in the setting of a multimodal quality improvement intervention Objective To elicit prescribers ' preferences for behavioural economics interventions design ed to reduce inappropriate antibiotic prescribing , and compare these to actual behaviour . Design Discrete choice experiment ( DCE ) . Setting 47 primary care centres in Boston and Los Angeles . Participants 234 primary care providers , with an average 20 years of practice . Main outcomes and measures Results of a behavioural economic intervention trial were compared to prescribers ' stated preferences for the same interventions relative to monetary and time rewards for improved prescribing outcomes . In the r and omised controlled trial ( RCT ) component , the 3 computerised prescription order entry-triggered interventions studied included : Suggested Alternatives ( SA ) , an alert that populated non-antibiotic treatment options if an inappropriate antibiotic was prescribed ; Accountable Justifications ( JA ) , which prompted the prescriber to enter a justification for an inappropriately prescribed antibiotic that would then be documented in the patient 's chart ; and Peer Comparison ( PC ) , an email periodically sent to each prescriber comparing his/her antibiotic prescribing rate with those who had the lowest rates of inappropriate antibiotic prescribing . A DCE study component was administered to determine whether prescribers felt SA , JA , PC , pay-for-performance or additional clinic time would most effectively reduce their inappropriate antibiotic prescribing . Willingness-to-pay ( WTP ) was calculated for each intervention . Results In the RCT , PC and JA were found to be the most effective interventions to reduce inappropriate antibiotic prescribing , whereas SA was not significantly different from controls . In the DCE however , regardless of treatment intervention received during the RCT , prescribers overwhelmingly preferred SA , followed by PC , then JA . WTP estimates indicated that each intervention would be significantly cheaper to implement than pay-for-performance incentives of $ 200/month . Conclusions Prescribing behaviour and stated preferences are not concordant , suggesting that relying on stated preferences alone to inform intervention design may eliminate effective interventions . Trial registration number NCT01454947 ; Results Background Between 30 and 40 % of patients with severe injuries receive treatment at non-trauma centers ( under-triage ) , largely because of physician decision making . Existing interventions to improve triage by physicians ignore the role that intuition ( heuristics ) plays in these decisions . One such heuristic is to form an initial impression based on representativeness ( how typical does a patient appear of one with severe injuries ) . We created a video game ( Night Shift ) to recalibrate physician ’s representativeness heuristic in trauma triage . Methods We developed Night Shift in collaboration with emergency medicine physicians , trauma surgeons , behavioral scientists , and game design ers . Players take on the persona of And y Jordan , an emergency medicine physician , who accepts a new job in a small town . Through a series of cases that go awry , they gain experience with the context ual cues that distinguish patients with minor and severe injuries ( based on the theory of analogical encoding ) and receive emotionally-laden feedback on their performance ( based on the theory of narrative engagement ) . The planned study will compare the effect of Night Shift with that of an educational program on physician triage decisions and on physician heuristics . Psychological theory predicts that cognitive load increases reliance on heuristics , thereby increasing the under-triage rate when heuristics are poorly calibrated . We will r and omize physicians ( n = 366 ) either to play the game or to review an educational program , and will assess performance using a vali date d virtual simulation . The vali date d simulation includes both control and cognitive load conditions . We will compare rates of under-triage after exposure to the two interventions ( primary outcome ) and will compare the effect of cognitive load on physicians ’ under-triage rates ( secondary outcome ) . We hypothesize that : a ) physicians exposed to Night Shift will have lower rates of under-triage compared to those exposed to the educational program , and b ) cognitive load will not de grade triage performance among physicians exposed to Night Shift as much as it will among those exposed to the educational program . Discussion Serious games offer a new approach to the problem of poorly-calibrated heuristics in trauma triage . The results of this trial will contribute to the underst and ing of physician quality improvement and the efficacy of video games as behavioral interventions .Trial registration clinical trials.gov ; NCT02857348 ; August 2 , 2016 IMPORTANCE Healthcare overuse , the delivery of low-value services , is increasingly recognized as a critical problem . However , little is known about the comparative effectiveness of alternate formats for presenting benefits and harms information to patients as a strategy to reduce overuse . OBJECTIVE To examine the effect of different benefits and harms presentations on patients ' intentions to accept low-value or potentially low-value screening services ( prostate cancer screening in men ages 50 - 69 years ; osteoporosis screening in low-risk women ages 50 - 64 years ; or colorectal cancer screening in men and women ages 76 - 85 years ) . DESIGN , SETTING , AND PARTICIPANTS R and omized clinical trial of 775 individuals eligible to receive information about any 1 of the 3 screening services and scheduled for a visit with their clinician . Participants were r and omized to 1 of 4 intervention arms that differed in terms of presentation format : words , numbers , numbers plus narrative , and numbers plus framed presentation . The trial was conducted from September 2012 to June 2014 at 2 family medicine and 2 internal medicine practice s affiliated with the Duke Primary Care Research Consortium . The data were analyzed between May and September of 2015 . INTERVENTIONS One-page evidence -based decision support sheets on each of the 3 screening services , with benefits and harms information presented in 1 of 4 formats : words , numbers , numbers plus narratives , or numbers plus a framed presentation . MAIN OUTCOMES AND MEASURES The primary outcome was change in intention to accept screening ( on a response scale from 1 to 5 ) . Our secondary outcomes included general and disease-specific knowledge , perceived risk and consequences of disease , screening attitudes , perceived net benefit of screening , values clarity , and self-efficacy for screening . RESULTS We enrolled and r and omly allocated 775 individuals , aged 50 to 85 years , to 1 of 4 intervention arms : 195 to words , 192 to numbers , 196 to narrative , and 192 to framed formats . Intentions to accept screening were high before the intervention and change in intentions did not differ across intervention arms ( words , -0.07 ; numbers , -0.05 ; numbers plus narrative , -0.12 ; numbers plus framed presentation , -0.02 ; P = .57 for all comparisons ) . Change in other outcomes also showed no difference across intervention arms . Results were similar when stratified by screening service . CONCLUSIONS AND RELEVANCE Single , brief , written decision support interventions , such as the ones in this study , are unlikely to be sufficient to change intentions for screening . Alternate and additional interventions are needed to reduce overused screening services . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01694784 Background Healthcare professionals are rapidly adopting electronic health records ( EHRs ) . Within EHRs , seemingly innocuous menu design configurations can influence provider decisions for better or worse . Objective The purpose of this study was to examine whether the grouping of menu items systematic ally affects prescribing practice s among primary care providers . Participants We surveyed 166 primary care providers in a research network of practice s in the greater Chicago area , of whom 84 responded ( 51 % response rate ) . Respondents and non-respondents were similar on all observable dimensions except that respondents were more likely to work in an academic setting . Design The question naire consisted of seven clinical vignettes . Each vignette described typical signs and symptoms for acute respiratory infections , and providers chose treatments from a menu of options . For each vignette , providers were r and omly assigned to one of two menu partitions . For antibiotic-inappropriate vignettes , the treatment menu either listed over-the-counter ( OTC ) medications individually while grouping prescriptions together , or displayed the reverse partition . For antibiotic-appropriate vignettes , the treatment menu either listed narrow-spectrum antibiotics individually while grouping broad-spectrum antibiotics , or displayed the reverse partition . Main Measures The main outcome was provider treatment choice . For antibiotic-inappropriate vignettes , we categorized responses as prescription drugs or OTC-only options . For antibiotic-appropriate vignettes , we categorized responses as broad- or narrow-spectrum antibiotics . Key Results Across vignettes , there was an 11.5 percentage point reduction in choosing aggressive treatment options ( e.g. , broad-spectrum antibiotics ) when aggressive options were grouped compared to when those same options were listed individually ( 95 % CI : 2.9 to 20.1 % ; p = .008 ) . Conclusions Provider treatment choice appears to be influenced by the grouping of menu options , suggesting that the layout of EHR order sets is not an arbitrary exercise . The careful crafting of EHR order sets can serve as an important opportunity to improve patient care without constraining physicians ’ ability to prescribe what they believe is best for their patients Background . Presentation of information using survival or mortality ( i.e. , incidence ) curves offers a potentially powerful method of communication because such curves provide information about risk over time in a relatively simple graphic format . However , the effect of framing as survival versus mortality on underst and ing and treatment choice is not known . Methods . In this study , 451 individuals awaiting jury duty at the Philadelphia City Courthouse were r and omized to receive 1 of 3 question naires : ( 1 ) survival curves , ( 2 ) mortality curves , or ( 3 ) both survival and mortality curves . Each question naire included a brief description of a hypothetical treatment decision , survival curve graphs and /or mortality curve graphs presenting the outcome of the treatment , and questions measuring underst and ing of the information contained in the graphs and preference for undergoing treatment . After completing a brief practice exercise , participants were asked to answer questions assessing their ability to interpret single points on a curve and the difference between curves , and then to decide whether they would choose to undergo preventive surgery for 3 different scenarios in which the benefit of surgery varied . Results . Participants who received only survival curves or who received both survival and mortality curves were significantly more accurate in answering questions about the information than participants who received only mortality curves ( P < 0.05 ) . For 2 of the 3 treatment presentations , participants who received only mortality curves were significantly less likely to prefer preventive surgery than participants who received survival curves only or both survival and mortality curves ( P < 0.05 ) . The effect of framing on underst and ing was greatest among participants with less than a college education and among non-Caucasian participants . Conclusion . Framing graphic risk information as chance of death over time results in lower levels of underst and ing and less interest in preventive surgery than framing as chance of survival over time |
1,647 | 30,589,090 | A range of risk factors for the new onset of CM/TM , CDH , or related chronic headache diseases were identified with the strongest data supporting increased headache day frequency , acute medication overuse/high-frequency use and depression , which are potentially modifiable risk factors .
Development of central sensitization and increased activation of the trigeminal nociceptive pathways may be drivers of the new onset of CM or CDH . | BACKGROUND Migraine is a common and often debilitating neurological disease .
It can be divided into episodic and chronic subforms based on the number of monthly headache days .
Because only a subset of individuals with episodic migraine ( EM ) progress to chronic migraine ( CM ) over any given time period , underst and ing the factors that predict the new onset of CM or " migraine progression " may provide insights into the mechanisms , pathophysiology , prevention , and treatment of CM .
In this review , we identify and summarize studies that report risk factors associated with the new onset of CM or related chronic headache diagnoses , group these risk factors and report the strength of evidence for the identified risk factors .
OBJECTIVE To conduct a systematic review of studies that identify risk factors for the new onset of CM or related chronic headache diagnoses such as transformed migraine ( TM ) and chronic daily headache ( CDH ) . | BACKGROUND Migraine frequently co-occurs with and is triggered by sleep disturbance , particularly insomnia , and the large majority of patients with chronic migraine ( CM ) have comorbid insomnia . Limited evidence suggests that behavioral regulation of sleep may reduce migraine frequency , but studies to date have not assessed the viability of stimulus control and sleep restriction interventions or included objective measurement of sleep parameters . The aim of this study , thus , was to pilot-test the efficacy of a brief behavioral insomnia intervention for adults with CM and comorbid insomnia ; headache diaries and actigraphy were included to assess outcomes throughout the trial . METHODS This r and omized parallel-arm pilot trial recruited adults with both CM and comorbid insomnia . Participants were r and omly assigned to three 30-minute biweekly sessions of cognitive-behavioral therapy for insomnia ( CBTi ) or control treatment . Participants were blinded to treatment and control conditions to control for outcome expectations . Each treatment condition involved training in and daily practice in 5 instructions/skills . The CBTi group learned and practice d skills pertaining to stimulus control and sleep restriction . The control intervention was the same as used by Calhoun and Ford ( 2007 ) and involved training in and daily practice of skills pertaining to keeping a consistent food/liquid intake , range of motion exercises , and acupressure . Participants provided outcome data via daily headache diaries , actigraphy , and self-report measures . The primary outcome was reduction in headache frequency at 2 weeks post-treatment and 6-week follow-up ; secondary outcomes included other headache parameters , objective actigraphic and subjective changes in sleep , and treatment effect sizes and perceived credibility . Generalized estimating equations with a binomial logit link and inverse probability weights were used to assess the primary outcome among the intent-to-treat sample , and repeated measures generalized linear models were used to assess changes in secondary outcomes after controlling for baseline values . RESULTS The intent-to-treat analyses included 31 adults ( M age = 30.8 [ 12.9 ] years ; 90.3 % female ; 80.6 % white ) with CM and comorbid insomnia . Both interventions yielded reductions in headache frequency at post-treatment ( 26.9 % reduction for CBTi vs. 36.2 % for control ) and follow-up ( 48.9 % for CBTi vs. 25.0 % for control ) . At follow-up the odds of experiencing headache were 60 % lower for CBTi than for control treatment , indicative of a large effect size that did not reach statistical significance after Bonferroni correction for assessing two primary endpoints ( odds ratio : 0.40 ; 95 % CI : 0.17 , 0.91 ; P = .028 ) . CBTi produced significantly larger increases than control treatment in total sleep time and sleep efficiency as quantified by actigraphy , as well as in self-reported insomnia severity . Adherence was high and treatments were perceived as credible without differences between groups , but the control group experienced a higher rate of dropouts . No adverse events were reported . CONCLUSIONS Behavioral treatment of comorbid insomnia in individuals with CM produced large reductions in headache frequency , though some improvement in headache occurred with a behavioral intervention not focused on modifying sleep . Among the CBTi group only , both headache frequency and sleep parameters continued to improve after treatment , suggesting the presence of enduring effects over time . Directly treating insomnia using components of stimulus control and sleep restriction holds promise for reducing comorbid migraine . Development of and comparison to a truly inert pseudotherapy control presents unique challenges that future studies should address CONTEXT A previous cross-sectional study showed an association of migraine with a higher prevalence of magnetic resonance imaging (MRI)-measured ischemic lesions in the brain . OBJECTIVE To determine whether women or men with migraine ( with and without aura ) have a higher incidence of brain lesions 9 years after initial MRI , whether migraine frequency was associated with progression of brain lesions , and whether progression of brain lesions was associated with cognitive decline . DESIGN , SETTING , AND PARTICIPANTS In a follow-up of the 2000 Cerebral Abnormalities in Migraine , an Epidemiological Risk Analysis cohort , a prospect i ve population -based observational study of Dutch participants with migraine and an age- and sex-matched control group , 203 of the 295 baseline participants in the migraine group and 83 of 140 in the control group underwent MRI scan in 2009 to identify progression of MRI-measured brain lesions . Comparisons were adjusted for age , sex , hypertension , diabetes , and educational level . The participants in the migraine group were a mean 57 years ( range , 43 - 72 years ) , and 71 % were women . Those in the control group were a mean 55 years ( range , 44 - 71 years ) , and 69 % were women . MAIN OUTCOME MEASURES Progression of MRI-measured cerebral deep white matter hyperintensities , infratentorial hyperintensities , and posterior circulation territory infa rct like lesions . Change in cognition was also measured . RESULTS Of the 145 women in the migraine group , 112 ( 77 % ) vs 33 of 55 women ( 60 % ) in the control group had progression of deep white matter hyperintensities ( adjusted odds ratio [ OR ] , 2.1 ; 95%CI , 1.0 - 4.1 ; P = .04 ) . There were no significant associations of migraine with progression of infratentorial hyperintensities : 21 participants ( 15 % ) in the migraine group and 1 of 57 participants ( 2 % ) in the control group showed progression ( adjusted OR , 7.7 ; 95 % CI , 1.0 - 59.5 ; P = .05 ) or new posterior circulation territory infa rct like lesions : 10 of 203 participants ( 5 % ) in the migraine group but none of 83 in the control group ( P = .07 ) . There was no association of number or frequency of migraine headaches with progression of lesions . There was no significant association of high vs nonhigh deep white matter hyperintensity load with change in cognitive scores ( -3.7 in the migraine group vs 1.4 in the control group ; 95 % CI , -4.4 to 0.2 ; adjusted P = .07 ) . CONCLUSIONS In a community-based cohort followed up after 9 years , women with migraine had a higher incidence of deep white matter hyperintensities but did not have significantly higher progression of other MRI-measured brain changes . There was no association of migraine with progression of any MRI-measured brain lesions in men Objective To test whether behavioral weight loss ( BWL ) intervention decreases headaches in women with comorbid migraine and overweight/obesity . Methods This r and omized , single-blind trial allocated women [ 18–50 years old , 4–20 migraine days/month , Body Mass Index ( BMI ) = 25.0–49.9 kg/m2 ] to 16 weeks of BWL , ( n=54 ) that targeted exercise and eating behaviors for weight loss , or Migraine Education control ( ME , n=56 ) that delivered didactic instruction on migraine and treatments . Participants completed a 4-week smartphone headache diary at baseline , post-treatment ( 16–20 weeks ) and follow-up ( 32–36 weeks ) . The primary outcome was post-treatment change in migraine days/month , analyzed via linear mixed effects models . Results Of 110 participants r and omized , 85 ( 78 % ) and 80 ( 73 % ) completed post-treatment and follow-up . Although BWL achieved greater weight loss [ mean ( 95 % CI ) kg ] vs. ME at post-treatment [ −3.8 ( −2.5 , −5.0 ) vs. + 0.9 ( −0.4,2.2 ) p<.001 ] and follow-up [ −3.2 ( −2.0 , −4.5 ) vs. + 1.1 ( −0.2,2.4 ) , p<.001 ] , there were no significant group ( BWL vs. ME ) differences [ mean ( 95%CI ) ] migraine days/month at post-treatment [ −3.0 ( −2.0 , −4.0 ) vs. −4.0 ( −2.9 , −5.0 ) , p=.185 ] or follow-up [ −3.8 ( −2.7 , −4.8 ) vs. −4.4 ( −3.4 , −5.5 ) , p=.378 ] . Conclusion Contrary to hypotheses , BWL and ME yielded similar , sustained reductions in migraine headaches . Future research should evaluate whether adding BWL to st and ard pharmacologic and /or non-pharmacologic migraine treatment approaches yields greater benefits Chronic daily headache ( CDH ) , when defined as ≥ 15 headache days per month , affects 3 - 5 % of the adult population . Major life changes are putative precipitating events for onset of chronic pain , including chronic headache . This study compared the occurrence of specific life events between CDH cases and episodic headache controls in a community sample . CDH cases ( 180 + headache days per year : n = 206 ) and episodic headache controls ( 2 - 104 headache days per year : n = 507 ) were identified from a r and omly selected adult US population . Subjects were interviewed about the occurrence of certain major life changes or events ( change of residence , employment status , marital status , related to their children , deaths of relatives or close friends , and ‘ extremely stressful ’ ongoing situations ) occurring in a defined time period . Events that occurred during the same year or year before frequent headache onset in cases or in an equivalent time period in controls were considered to be antecedent events . Those that occurred after this time were considered subsequent events . Compared with episodic headache controls , CDH cases had more major life changes in the year before or same year as CDH onset . After adjusting for age , gender , headache type and year of event , the odds of CDH increased additionally with each antecedent event [ odds ratio ( OR ) 1.20 ( 1.1 , 1.3 ) , P < 0.001 ] , but not with subsequent events [ OR 0.94 ( 0.8 , 1.1 ) , P < 0.4 ] . In secondary analyses , the association between antecedent events and CDH was significant only for the approximately half of CDH cases who were aged ≥ 40 years [ OR 1.33 ( 1.2 , 1.50 ) vs. OR 1.04 ( 0.9 , 1.2 ) , P < 0.05 for interaction by age ] . These results suggest that major life changes are associated with the onset of chronic daily headache , particularly in middle age Objectives : Research increasingly suggests that obesity is an exacerbating factor for migraine . However , it is less clear whether weight loss may help to alleviate migraine in obese individuals . We examined whether weight loss after bariatric surgery is associated with improvements in migraine headaches . Methods : In this prospect i ve observational study , 24 patients who had migraine according to the ID-Migraine screener were assessed before and 6 months after bariatric surgery . At both time points , patients had their weight measured and reported on frequency of headache days , average headache pain severity , and headache-related disability over the past 90 days via the Migraine Disability Assessment question naire . Changes in headache measures and the relation of weight loss to these changes were assessed using paired- sample t tests and logistic regression , respectively . Results : Patients were mostly female ( 88 % ) , middle-aged ( mean age 39.3 ) , and severely obese ( mean body mass index 46.6 ) at baseline . Mean ( ±SD ) number of headache days was reduced from 11.1 ± 10.3 preoperatively to 6.7 ± 8.2 postoperatively ( p < 0.05 ) , after a mean percent excess weight loss ( % EWL ) of 49.4 % . The odds of experiencing a ≥50 % reduction in headache days was related to greater % EWL , independent of surgery type ( p < 0.05 ) . Reductions in severity were also observed ( p < 0.05 ) and the number of patients reporting moderate to severe disability decreased from 12 ( 50.0 % ) before surgery to 3 ( 12.5 % ) after surgery ( p < 0.01 ) . Conclusions : Severely obese migraineurs experience marked alleviation of headaches after significant weight reduction via bariatric surgery . Future studies are needed to determine whether more modest , behaviorally produced weight losses can effect similar migraine improvements . Classification of evidence : This study provides Class III evidence that bariatric surgery is associated with reduction of migraine headaches in severely obese individuals BACKGROUND Sleep problems have been linked with headaches for more than a century , but whether the headaches are the cause or the result of the disrupted sleep is unknown . OBJECTIVES We previously reported that nonrestorative sleep and poor sleep habits are almost universal in a referral population of women with transformed migraine ( TM ) . Since cognitive behavioral therapy is effective in improving sleep quality in individuals with poor sleep hygiene , we design ed a r and omized , placebo-controlled study to assess the impact of such treatment on TM . We hypothesized that behavioral sleep modification ( BSM ) would be associated with improvement in headache frequency and intensity and with reversion to episodic migraine . METHODS Subjects were 43 women with TM referred to an academic headache center . After obtaining informed consent , patients were r and omized to receive either behavioral sleep instructions or placebo behavioral instructions in addition to usual medical care . Subjects recorded headaches in st and ardized diaries . The first postintervention visit was scheduled at 6 weeks . At that visit , the blind was broken and all subjects received BSM instructions . A final visit was scheduled 6 weeks later . RESULTS Compared to the placebo behavioral group , the BSM group reported statistically significant reduction in headache frequency [ F ( 1 , 33 = 12.42 , P=.001 ) ] and headache intensity [ F(1 , 33 = 14.39 , P= .01 ) ] . They were more likely to revert to episodic migraine chi2 ( 2 , n = 43 ) = 7.06 , P= .029 . No member of the control group reverted to episodic migraine by the first postintervention visit . By the final visit , 48.5 % of those who had received BSM instructions had reverted to episodic migraine . CONCLUSIONS In this pilot study of women with TM , we found that a targeted behavioral sleep invention was associated with improvement in headache frequency , headache index , and with reversion to episodic migraine Background Chronic migraine is associated with significant headache-related disability and psychiatric comorbidity . OnabotulinumtoxinA ( BOTOX ® ) is effective and well tolerated in the prophylactic treatment of chronic migraine . This study aim ed to provide preliminary data on the efficacy and safety of prophylactic onabotulinumtoxinA in patients with chronic migraine and comorbid depressive symptoms . Methods This was a prospect i ve , open-label , multicenter pilot study . Eligible patients met International Classification of Headache Disorders 2nd edition Revision criteria for chronic migraine and had associated depressive symptoms , including Patient Health Question naire depression module scores of 5–19 . Eligible participants received 155 units of onabotulinumtoxinA , according to the PREEMPT protocol , at baseline and week 12 . Assessment s included headache frequency , the Headache Impact Test ™ , the Migraine Disability Assessment , the Beck Depression Inventory ® -II , the nine-item Patient Health Question naire depression module , and the seven-item Generalized Anxiety Disorder question naire . Adverse events were also monitored . Results Overall , 32 participants received treatment . At week 24 , there were statistically significant mean ( st and ard deviation [ SD ] ) improvements relative to baseline in the number of headache/migraine-free days ( + 8.2 [ 5.8 ] ) ( P<0.0001 ) and in the number of headache/migraine days ( −8.2 [ 5.8 ] ) ( P<0.0001 ) per 30-day period . In addition , there were significant improvements in Headache Impact Test scores ( −6.3 [ 6.9 ] ) ( P=0.0001 ) and Migraine Disability Assessment scores ( −44.2 [ 67.5 ] ) ( P=0.0058 ) . From baseline to week 24 , statistically significant improvements were also seen in Beck Depression Inventory-II ( −7.9 [ 6.0 ] ) ( P<0.0001 ) , Patient Health Question naire depression module ( −4.3 [ 4.7 ] ) ( P<0.0001 ) , and Generalized Anxiety Disorder question naire ( −3.5 [ 5.0 ] ) ( P=0.0002 ) scores . No serious adverse events were reported . Adverse events considered related to treatment occurred in 30 % of patients and were mild or moderate . Conclusion Prophylactic onabotulinumtoxinA was well tolerated in patients with chronic migraine and comorbid depression , and was effective in reducing headache frequency , impact , and related disability , which led to statistically significant improvements in depression and anxiety symptoms Background Longitudinal migraine studies have rarely assessed headache frequency and disability variation over a year . Methods The Chronic Migraine Epidemiology and Outcomes ( CaMEO ) Study is a cross-sectional and longitudinal Internet study design ed to characterize the course of episodic migraine ( EM ) and chronic migraine ( CM ) . Participants were recruited from a Web-panel using quota sampling in an attempt to obtain a sample demographically similar to the US population . Participants who passed the screener were assessed every three months with the Core ( baseline , six , and 12 months ) and Snapshot ( months three and nine ) modules , which assessed headache frequency , headache-related disability , treatments , and treatment satisfaction . The Core also assessed re source use , health-related quality of life , and other features . One-time cross-sectional modules measured family burden , barriers to medical care , and comorbidities/endophenotypes . Results Of 489,537 invitees , we obtained 58,418 ( 11.9 % ) usable returns including 16,789 individuals who met ICHD-3 beta migraine criteria ( EM ( < 15 headache days/mo ) : n = 15,313 ( 91.2 % ) ; CM ( ≥15 headache days/mo ) : n = 1476 ( 8.8 % ) ) . At baseline , all qualified respondents ( n = 16,789 ) completed the Screener , Core , and Barriers to Care modules . Subsequent modules showed some attrition ( Comorbidities/Endophenotypes , n = 12,810 ; Family Burden ( Prob and ) , n = 13,064 ; Family Burden ( Partner ) , n = 4022 ; Family Burden ( Child ) , n = 2140 ; Snapshot ( three months ) , n = 9741 ; Core ( six months ) , n = 7517 ; Snapshot ( nine months ) , n = 6362 ; Core ( 12 months ) , n = 5915 ) . A total of 3513 respondents ( 21.0 % ) completed all modules , and 3626 ( EM : n = 3303 ( 21.6 % ) ; CM : n = 323 ( 21.9 % ) ) completed all longitudinal assessment s. Conclusions The CaMEO Study provides cross-sectional and longitudinal data that will contribute to our underst and ing of the course of migraine over one year and quantify variations in headache frequency , headache-related disability , comorbidities , treatments , and familial impact The aim of this study was to assess the role of depression as a predictor of new onset of chronic migraine ( CM ) among persons with episodic migraine ( EM ) . The American Migraine Prevalence and Prevention ( AMPP ) study followed 24,000 persons with severe headache identified in 2004 . Using r and om-effects logistic regression , we modeled the probability that persons with EM in 2005 or 2006 would develop CM in the subsequent year . Depression was assessed in two ways , using a vali date d question naire ( PHQ-9 score ≥15 ) and based on self-reported medical diagnosis . Analyses were adjusted for multiple covariates including sociodemographics , body mass index , headache pain intensity , headache frequency , migraine symptom severity , cutaneous allodynia , acute medication overuse , anti-depressant use and anxiety . Of 6,657 participants with EM in 2005 , 160 ( 2.4 % ) developed CM in 2006 . Of 6,852 participants with EM in 2006 , 144 ( 2.2 % ) developed CM in 2007 . In fully adjusted models , PHQ-9 defined depression was a significant predictor of CM onset [ odds ratio ( OR ) = 1.65 , 95 % CI 1.12–2.45 ] . There was a depression-dose effect ; relative to participants with no depression or mild depression , those with moderate ( OR = 1.77 , 95 % CI 1.25–2.52 ) , moderately severe ( OR = 2.35 , 95 % CI 1.53–3.62 ) , and severe depression ( OR = 2.53 , 95 % CI 1.52–4.21 ) were at increased risk for the onset of CM . Among persons with EM , depression was associated with an increased risk of CM after adjusting for sociodemographic variables and headache characteristics . Depression preceded the onset of CM and risk increased with depression severity suggesting a potentially causal role though reverse causality can not be excluded CONTEXT Clinical series have suggested an increased prevalence of cerebral infa rct ion and white matter lesions ( WMLs ) in migraine patients . It is not known whether these lesions are prevalent in the general migraine population . OBJECTIVES To compare the prevalence of brain infa rcts and WMLs in migraine cases and controls from the general population and to identify migraine characteristics associated with these lesions . DESIGN Cross-sectional , prevalence study of population -based sample of Dutch adults aged 30 to 60 years . PARTICIPANTS R and omly selected patients with migraine with aura ( n = 161 ) , patients with migraine without aura ( n = 134 ) , and controls ( n = 140 ) , who were frequency matched to cases for age , sex , and place of residence . Nearly 50 % of the cases had not been previously diagnosed by a physician . MAIN OUTCOME MEASURES Brain magnetic resonance images were evaluated for infa rcts , by location and vascular supply territory , and for periventricular WMLs ( PVWMLs ) and deep WMLs ( DWMLs ) . The odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) of these brain lesions compared with controls were examined by migraine subtype ( with or without aura ) and monthly attack frequency ( < 1 attack , > or = 1 attack ) , controlling for cardiovascular risk factors and use of vasoconstrictor migraine agents . All participants underwent a st and ard neurological examination . RESULTS No participants reported a history of stroke or transient ischemic attack or had relevant abnormalities at st and ard neurological examination . We found no significant difference between patients with migraine and controls in overall infa rct prevalence ( 8.1 % vs 5.0 % ) . However , in the cerebellar region of the posterior circulation territory , patients with migraine had a higher prevalence of infa rct than controls ( 5.4 % vs 0.7 % ; P = .02 ; adjusted OR , 7.1 ; 95 % CI , 0.9 - 55 ) . The adjusted OR for posterior infa rct varied by migraine subtype and attack frequency . The adjusted OR was 13.7 ( 95 % CI , 1.7 - 112 ) for patients with migraine with aura compared with controls . In patients with migraine with a frequency of attacks of 1 or more per month , the adjusted OR was 9.3 ( 95 % CI , 1.1 - 76 ) . The highest risk was in patients with migraine with aura with 1 attack or more per month ( OR , 15.8 ; 95 % CI , 1.8 - 140 ) . Among women , the risk for high DWML load ( top 20th percentile of the distribution of DWML load vs lower 80th percentile ) was increased in patients with migraine compared with controls ( OR , 2.1 ; 95 % CI , 1.0 - 4.1 ) ; this risk increased with attack frequency ( highest in those with > or = 1 attack per month : OR , 2.6 ; 95 % CI , 1.2 - 5.7 ) but was similar in patients with migraine with or without aura . In men , controls and patients with migraine did not differ in the prevalence of DWMLs . There was no association between severity of PVWMLs and migraine , irrespective of sex or migraine frequency or subtype . CONCLUSIONS These population -based findings suggest that some patients with migraine with and without aura are at increased risk for sub clinical lesions in certain brain areas To assess the prevalence and possible pathogenetic involvement of raised intracranial pressure in patients presenting with unresponsive chronic migraine ( CM ) , we evaluated the intracranial opening pressure ( OP ) and clinical outcome of a single cerebrospinal fluid withdrawal by lumbar puncture in 44 consecutive patients diagnosed with unresponsive chronic/transformed migraine and evidence of sinus stenosis at magnetic resonance venography . The large majority of patients complained of daily or near-daily headache . Thirty-eight ( 86.4 % ) had an OP > 200 mmH2O . Lumbar puncture-induced normalization of intracranial pressure result ed in prompt remission of chronic pain in 34/44 patients ( 77.3 % ) ; and an episodic pattern of headache was maintained for 2 , 3 and 4 months in 24 ( 54.6 % ) , 20 ( 45.4 % ) and 17 ( 38.6 % ) patients , respectively . The medians of overall headache days/month and of disabling headache days/month significantly decreased ( p < 0.0001 ) at each follow-up versus baseline . Despite the absence of papilledema , 31/44 ( 70.5 % ) patients fulfilled the ICHD-II criteria for “ Headache attributed to Intracranial Hypertension ” . Our findings indicate that most patients diagnosed with unresponsive CM in specialized headache clinics may present an increased intracranial pressure involved in the progression and refractoriness of pain . Moreover , a single lumbar puncture with cerebrospinal fluid withdrawal results in sustained remission of chronic pain in many cases . Prospect i ve controlled studies are needed before this procedure can be translated into clinical practice . Nonetheless , we suggest that intracranial hypertension without papilledema should be considered in all patients with almost daily migraine pain , with evidence of sinus stenosis , and unresponsive to medical treatment referred to specialized headache clinics BACKGROUND The International Classification of Headache Disorders provides criteria for the diagnosis and subclassification of migraine . Since there is no objective gold st and ard by which to test these diagnostic criteria , the criteria are based on the consensus opinion of content experts . Accurate migraine classifiers consisting of brain structural measures could serve as an objective gold st and ard by which to test and revise diagnostic criteria . The objectives of this study were to utilize magnetic resonance imaging measures of brain structure for constructing classifiers : ( 1 ) that accurately identify individuals as having chronic vs episodic migraine vs being a healthy control ; and ( 2 ) that test the currently used threshold of 15 headache days/month for differentiating chronic migraine from episodic migraine . METHODS Study participants underwent magnetic resonance imaging for determination of regional cortical thickness , cortical surface area , and volume . Principal components analysis combined structural measurements into principal components accounting for 85 % of variability in brain structure . Models consisting of these principal components were developed to achieve the classification objectives . Tenfold cross validation assessed classification accuracy within each of the 10 runs , with data from 90 % of participants r and omly selected for classifier development and data from the remaining 10 % of participants used to test classification performance . Headache frequency thresholds ranging from 5 - 15 headache days/month were evaluated to determine the threshold allowing for the most accurate subclassification of individuals into lower and higher frequency subgroups . RESULTS Participants were 66 migraineurs and 54 healthy controls , 75.8 % female , with an average age of 36 + /- 11 years . Average classifier accuracies were : ( 1 ) 68 % for migraine ( episodic + chronic ) vs. healthy controls ; ( 2 ) 67.2 % for episodic migraine vs healthy controls ; ( 3 ) 86.3 % for chronic migraine vs. healthy controls ; and ( 4 ) 84.2 % for chronic migraine vs episodic migraine . The classifiers contained principal components consisting of several structural measures , commonly including the temporal pole , anterior cingulate cortex , superior temporal lobe , entorhinal cortex , medial orbital frontal gyrus , and pars triangularis . A threshold of 15 headache days/month allowed for the most accurate subclassification of migraineurs into lower frequency and higher frequency subgroups . CONCLUSIONS Classifiers consisting of cortical surface area , cortical thickness , and regional volumes were highly accurate for determining if individuals have chronic migraine . Furthermore , results provide objective support for the current use of 15 headache days/month as a threshold for dividing migraineurs into lower frequency ( i.e. , episodic migraine ) and higher frequency ( i.e. , chronic migraine ) subgroups Objective : To identify patterns of noncephalic pain comorbidity in people with episodic migraine ( EM ; < 15 headache-days per month ) and chronic migraine ( CM ; ≥15 headache-days per month ) and to examine whether the presence of noncephalic pain is an indicator for the 3-month onset or persistence of CM . Methods : Data from the Chronic Migraine Epidemiology and Outcomes ( CaMEO ) Study , a prospect i ve , web-based study with cross-sectional modules embedded in a longitudinal design , were analyzed at baseline and the 3-month follow-up . Relationships between the number of noncephalic pain sites and 3-month onset of CM or persistent CM were assessed . Results : Of 8,908 eligible respondents , 8,139 ( 91.4 % ) had EM and 769 ( 8.6 % ) had CM at baseline . At 3 months , the incidence of CM among those with baseline EM was 3.4 % . When adjusted for demographics and headache-day frequency , the odds of CM onset among those with baseline EM increased by 30 % ( 95 % confidence interval [ CI ] 1.21–1.40 , p < 0.001 ) for each additional noncephalic pain site at baseline . Among those with CM at baseline , 50.1 % had persistent CM at the 3-month follow-up . After adjustment for demographics , individuals with CM were 15 % ( 95 % CI 1.07–1.25 , p < 0.001 ) more likely to have persistent CM for each additional noncephalic pain site at baseline . Conclusions : These results suggest that noncephalic pain may be a marker for headache chronicity that could be used to identify people with EM at risk of the onset of CM and people with CM at risk of persistent CM Background : An association between migraine and major depression has been observed in clinical and community sample s. The factors that contribute to this association and their implication s remain unclear . Objective : To determine the factors contributing to the association of migraine and major depression . Methods : A cohort study of persons aged 25 to 55 years with migraine ( n = 496 ) or with other headaches of comparable severity ( n = 151 ) and control subjects with no history of severe headaches ( n = 539 ) r and omly selected from the general community were interviewed first in 1997 and then reinterviewed in 1999 . Results : Major depression at baseline predicted the first-onset migraine during the 2-year follow-up period ( odds ratio [ OR ] = 3.4 ; 95 % CI = 1.4 , 8.7 ) but not other severe headaches ( OR = 0.6 ; 95 % CI = 0.1 , 4.6 ) . Migraine at baseline predicted the first-onset major depression during follow-up ( OR = 5.8 ; 95 % CI = 2.7 , 12.3 ) ; the prospect i ve association from severe headaches to major depression was not significant ( OR = 2.7 ; 95 % CI = 0.9 , 8.1 ) . Comorbid major depression did not influence the frequency of migraine attacks , their persistence , or the progression of migraine-related disability over time . Conclusions : Major depression increased the risk for migraine , and migraine increased the risk for major depression . This bidirectional association , with each disorder increasing the risk for first onset of the other , was not observed in relation to other severe headaches . With respect to other severe headaches , there was no increased risk associated with pre-existing major depression , although the possibility of an influence in the reverse direction ( i.e. , from severe headaches to depression ) can not be securely ruled out OBJECTIVES To measure longitudinally headache ( HA ) after moderate and severe traumatic brain injury ( TBI ) and to examine potential association with demographic , injury , and psychologic factors . DESIGN Cohort study . SETTING Four Veterans Administration rehabilitation facilities ( Minneapolis , Palo Alto , Richmond , Tampa ) within the Defense and Veterans Brain Injury Center . PARTICIPANTS Consecutive patients ( military or veteran beneficiaries ) with moderate or severe TBI ( N=109 ) who during acute rehabilitation consented to data collection and who completed 6- and 12-month follow-up evaluations . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES HA frequency , location , type , and incapacitation levels measured during prospect i ve neurologic assessment s. RESULTS Nearly 38 % ( 41/109 ) of patients had acute posttraumatic headache ( PTHA ) symptoms ; most often in a frontal location ( 20/41 ) , most often of daily frequency ( 31/41 ) , and showing no relation to injury severity , emotional , or demographic variables . Postacutely , PTHA symptom severity declined within the group . Better individual improvement was associated with less anxiety and depression at 6-month follow-up . Almost all subjects ( 21/22 ) with PTHA symptoms that persisted into the 6-month follow-up period reported symptoms again at 12-month follow-up . CONCLUSIONS PTHA severity in this sample of persons with moderate and severe TBI showed a pattern of improvement that leveled off by 6 months posthospitalization Objective : To evaluate the extent to which head and neck injury ( HANI ) contributes to chronic daily headache ( CDH ) . Background : In prospect i ve studies , head injury is associated with headache ( HA ) that remains a problem at 12 to 24 months post-head injury in 20 to 30 % of patients . Of these , up to 30 to 50 % manifest CDH . The degree to which head injury contributes to CDH has not been evaluated in a non- clinical population . We evaluate the relationship between lifetime occurrence of HANI and CDH in a r and omly chosen population sample . Methods : Study participants are from the Frequent Headache Epidemiology Study . Cases with CDH ( ≥180 HA/year ) and a comparison group with episodic headache ( EH , 2 to 102 HA/year ) were identified from the general population . Subjects were asked about lifetime occurrence of HANI . HANI were further classified as potentially precipitating injuries ( PPI ) if they occurred within 2 years of CDH onset for cases or in an equivalent 2-year period for EH controls . Results : Lifetime occurrence of HANI was more frequent in cases than controls for men ( adjusted OR = 3.1 [ 1.3 to 7.2 ] ) , women ( OR = 1.5 [ 0.97 to 2.3 ] ) , and overall ( OR = 1.7 [ 1.1 to 2.4 ] ) . The attributable risk was 15 % ( 36 % men , 11 % women ) . Results were similar for PPI . The odds of CDH increased with the number of lifetime HANI in all groups ( p < 0.05 trend ) . Conclusions : Results suggest that head and neck injury ( HANI ) accounts for approximately 15 % of chronic daily headache ( CDH ) cases in this non- clinical population . The relationship between HANI and CDH was not limited to injuries proximate to CDH onset . The lifetime risk of CDH increases with increasing number of HANI & NA ; Variations in the gene encoding catechol‐O‐methyltransferase ( COMT ) are linked to individual differences in pain sensitivity . A single nucleotide polymorphism ( SNP ) in codon 158 ( val158met ) , which affects COMT protein stability , has been associated with the human experience of pain . We recently demonstrated that three common COMT haplotypes , which affect the efficiency of COMT translation , are strongly associated with a global measure of pain sensitivity derived from individuals ’ responses to noxious thermal , ischemic , and pressure stimuli . Specific haplotypes were associated with low ( LPS ) , average ( APS ) , or high ( HPS ) pain sensitivity . Although these haplotypes included the val158met SNP , a significant association with val158met variants was not observed . In the present study , we examined the association between COMT genotype and specific pain‐evoking stimuli . Threshold and tolerance to thermal , ischemic , and mechanical stimuli , as well as temporal summation to heat pain , were determined . LPS/LPS homozygotes had the least , APS/APS homozygotes had average , and APS/HPS heterozygotes had the greatest pain responsiveness . Associations were strongest for measures of thermal pain . However , the rate of temporal summation of heat pain did not differ between haplotype combinations . In contrast , the val158met genotype was associated with the rate of temporal summation of heat pain , but not with the other pain measures . This suggests that the val158met SNP plays a primary role in variation in temporal summation of pain , but that other SNPs of the COMT haplotype exert a greater influence on resting nociceptive sensitivity . Here , we propose a mechanism whereby these two genetic polymorphisms differentially affect pain perception The objective of this study was to determine predictors of onset of new headache episodes and recovery from headache over one year . A population -based cohort study was conducted , comprising a baseline postal survey to a r and om sample of adults aged ≥18 years , with follow-up survey after 1 year . Risk factor data at baseline were compared with headache status at follow-up in two groups : ( i ) those free of recent headache at baseline and ( ii ) those with a recent headache at baseline . In respondents free of recent headache at baseline , previous headache [ risk ratio ( RR ) 4.15 ] , the presence of other pain at baseline ( RR 1.43 ) , severe sleep problems ( RR 1.67 ) and drinking caffeine ( RR 1.99 ) increased the risk of a new headache episode during the follow-up year . In respondents with recent headache at baseline , less severe headaches at baseline predicted recovery during the follow-up year , as did the absence of anxiety [ recovery ratio ( ReR ) 2.84 ] and of sleep problems ( ReR 2.77 ) . Risks for increased headache-related disability reflected those for onset of a new episode and these risks increased in strength for large increases in disability . Sleep problems and caffeine consumption increase the risk of developing headache and thus provide targets for prevention . Low levels of anxiety , sleep problems and the absence of other pain improve the likelihood of recovering and remaining free from headache OBJECTIVE To examine the potential influence of r and om measurement error on estimated rates of chronification and remission . BACKGROUND Studies of headache chronification and remission examine the proportion of headache sufferers that move across a boundary of 15 headache days per month between 2 points in time . At least part of that apparent movement may represent measurement error or r and om variation in headache activity over time . METHODS A mathematical simulation was conducted to examine the influence of varying degrees of measurement error on rates of chronic migraine onset and remission . Using data from the American Migraine Prevalence and Prevention Study , we estimated a starting distribution of headache days from 0 to 30 in the migraine population . Assuming various levels of measurement error , we then simulated 2 sets of data for Time 1 and Time 2 . The " individuals " in this study were assumed to have no real change in headache frequency from Time 1 to Time 2 . The observed variations in headache frequency were those influenced by imputed r and om variance to resemble typical measurement error or natural variability . Using this simulation approach , we estimated the amount of chronification and remission rates that might be attributed simply to statistical artifacts such as unreliability or regression to the mean . RESULTS As the degree of measurement error increased , the amounts of illusory chronification and remission increased substantially . For example , if the headache frequency of sufferers r and omly varies by only 2 headache days each month due to chance alone , a substantial degree of illusory chronification ( 0.6 % to 1.3 % ) and illusory remission ( 10.3 % to 23.5 % ) rates are expected simply due to r and om variation . CONCLUSIONS R and om variation , without real change , has the potential to influence estimated rates of progression and remission in longitudinal migraine studies . The magnitude of r and om variation needed to fully reproduce observed rates of progression and remission are implausibly large . Recommendations are offered to improve estimation of rates of progression and remission , reducing the influence of r and om variation BACKGROUND Though nausea is a cardinal feature of migraine , its influence on migraine progression has not been evaluated . This article aims to evaluate persistent frequent headache-related nausea ( PFN ) in persons with episodic migraine ( EM ) as a predictor of new onset chronic migraine ( CM ) . METHODS This prospect i ve cohort study uses data from the 2007 and 2008 American Migraine Prevalence and Prevention study surveys to identify subgroups with episodic International Classification of Headache Disorders , 2nd edition defined migraine and either PFN or no or low frequency nausea ( NLFN ) . PFN was defined by the presence of nausea ≥ half the time in both 2007 and 2008 . NLFN was defined by nausea that was present < half the time , rarely or never in both years . Persons were considered CM in 2009 if they met symptom criteria for migraine with headaches ≥15 days per month over the preceding 3 months . Univariate differences in demographics for PFN and NLFN were evaluated with chi-square . Binary logistic regressions were performed hierarchically to assess progression to CM in 2009 as a function of nausea status in 2007 and 2008 . The initial model included sociodemographic variables only . Subsequent models added the following variables in a hierarchical manner : migraine symptom severity composite score ( to control for the impact of other headache features ) , headache-related disability , depression , opioid use , and an interaction term for nausea status and opioid use . Odds ratios ( OR ) and 95 % confidence intervals ( CI ) contrasted PFN and NLFN on the rate of progression to CM in 2009 . RESULTS There were 3182 respondents with headache symptom and frequency data available for all 3 years of the analysis . PFN was found in 43.7 % ( 1389 ) of respondents , and 3.4 % ( 47 ) progressed to CM . NLFN was seen in 27.6 % ( 877 ) of the EM group , and 1.5 % progressed to CM . In comparison with the NLFN group , PFN was more common in females ( P<.001 ) and Caucasians ( P<.06 ) . PFN was associated with a doubling of the risk of progression to CM after adjusting for sociodemographic variables ( OR 2.09 , 95 % CI 1.11 - 3.91 , P=.022 ) . Adding the symptom composite score and headache-related disability covariates to the model attenuated the association slightly ( OR 2.00 , 95 % CI 1.03 - 3.87 , P=.04 ) . With the addition of depression , the association fell just below statistical significance but progression risk with PFN remained at nearly two-fold that of the NLFN group ( OR 1.90 , 95 % CI 0.98 - 3.71 , P=.059 ) . When opioid use and the nausea by opioid use interaction are added to the final model , the significant effect and the doubling of CM progression risk for those with PFN was retained ( OR 2.24 , 95 % CI 1.07 - 4.70 , P=.033 ) . CONCLUSIONS Persistent frequent nausea is common ( 43.7 % ) among persons with episodic migraine . After controlling for sociodemographics , migraine symptom severity , headache-related disability , depression , and opioid medication use , migraineurs with frequent nausea that persisted for 2 years of study were twice as likely to progress to CM compared to those with no or low frequency nausea . The study is limited by self-reports of symptom and headache frequency data and the use of modified diagnostic criteria . Additional prospect i ve research is needed to confirm study findings . Persistent frequent nausea could be a marker for the risk of progression to CM or it could be in the causal pathway We present the first prevalence study of specific headache entities using the operational diagnostic criteria of the International Headache Society . One thous and 25 - 64 year old men and women , who lived in the western part of Copenhagen County were r and omly drawn from the Danish National Central Person Registry . All subjects were invited to a general health examination focusing on headache and including : a self-administered question naire concerning sociodemographic variables , a structured headache interview and a general physical and neurological examination . The participation rate was 76 % . Information about 79 % of the non- participants showed a slightly differing headache prevalence which was not quantitatively important . The following results in participants are therefore representative of the total sample . The lifetime prevalences of headache ( including anybody with any form of headache ) , migraine , and tension-type headache were 93 , 8 and 69 % in men ; and 99 , 25 and 88 % in women . The point prevalence of headache was 11 % in men and 22 % in women . Prevalence of migraine in the previous year was 6 % in men and 15 % in women and the corresponding prevalences of tension-type headache were 63 and 86 % . Differences according to sex were significant with a male : female ratio of 1:3 in migraine , and 4:5 in tension-type headache . The prevalence of tension-type headache decreased with increasing age , whereas migraine showed no correlation to age within the studied age interval . Headache disorders are extremely prevalent and represent a major health problem , which merits increased attention BACKGROUND / PURPOSE The seven-item Migraine Disability Assessment ( MIDAS ) question naire is a simple and useful tool for evaluating migraine-related disability . The goals of this study were : ( 1 ) to test the reliability and validity of the Taiwan version of the MIDAS ( MIDAS-T ) question naire , and ( 2 ) to measure the impact of migraine among Taiwanese patients in a headache clinic . METHODS Consecutive migraine patients , aged 20 - 50 years , visiting the headache clinic at the Taipei Veterans General Hospital were invited to participate in the study . They completed the MIDAS-T and a form , which collected headache-related information including characteristics and impact on their lives . Of them , about 30 patients were r and omly invited to repeat the MIDAS-T 3 weeks later . RESULTS A total of 281 migraine patients ( M/F , 63/218 ; mean age , 35.27 + /- 8.21 years ) participated in the study . Of them , 31 completed the MIDAS-T again 3 weeks later . MIDAS-T showed acceptable internal consistency ( Cronbach alpha = 0.79 ) , test-retest reliability ( r = 0.67 ) and criterion validity ( r = 0.37 for question A [ headache frequency ] and r = 0.34 for question B [ headache intensity ] , p < 0.001 ) . The mean score of migraine patients on MIDAS-T was 34.21 + /- 45.90 , ranging from 0 to 265 . MIDAS grade I ( score 0 - 5 ) was found in 22 % of patients , grade II ( 6 - 10 ) in 15 % , grade III ( 11 - 20 ) in 17 % , and grade IV ( > or=21 ) in 46 % . CONCLUSION This study supports the reliability and validity of MIDAS-T for use in Taiwanese patients . Almost half of the migraine patients were classified as having severe disability ( grade IV ) Abstract Objectives : To determine the prevalence rates of the various causes of severe headache in school-children , with special emphasis on migraine and its impact on school attendance . Design : Population based study in two stages , comprising an initial screening question naire followed by clinical interviews and examination of children with symptoms and a control group of asymptomatic children matched for age and sex . Setting : 67 primary and secondary schools in the city of Aberdeen . Subjects : 2165 children , representing a r and om sample of 10 % of schoolchildren in Aberdeen aged 5 - 15 years . Main outcome measures : ( a ) the prevalence of20migraine ( International Headache Society criteria ) and of other types of headache ; ( b ) the impact of migraine on school attendance . Results : The estimated prevalence rates of migraine and tension headache were 10.6 % ( 95 % confidence interval 9.1 to 12.3 ) and 0.9 % ( 0.5 to 1.5 ) respectively . The estimated prevalence rates for migraine without aura and migraine with aura were 7.8 % ( 95 % confidence interval 6.5 to 9.3 ) and 2.8 % ( 2.0 to 3.8 ) respectively . In addition , 10 children ( 0.7 % ) had headaches which , though lasting less than two hours , also fulfilled the International Headache Society criteria for migraine , 14 ( 0.9 % ) had tension headaches , and 20 ( 1.3 % ) had non-specific recurrent headache . The prevalence of migraine increased with age , with male preponderance in children under 12 and female preponderance thereafter . Children with migraine lost a mean of 7.8 school days a year due to all illnesses ( 2.8 days ( range 0 - 80 ) due to headache ) as compared with a mean of 3.7 days lost by controls . Conclusions : Migraine is a common cause of headache in children and causes significantly reduced school attendance During the past decade , several population ‐based studies have found an inverse association between blood pressure ( BP ) and headache . However , most of them have a cross‐sectional design or lack a vali date d definition of a headache‐free population at baseline . Therefore , additional population ‐based studies using a clearly defined headache‐free population and a prospect i ve design are warranted Objective : The study sought to evaluate whether topiramate prevents development of chronic daily headache ( CDH , ≥15 headache days per month ) in adult subjects with high-frequency episodic migraine ( HFEM , 9–14 migraine headache days/month ) . A secondary objective was to assess the efficacy of topiramate as preventive migraine treatment in this population . Methods : This was a multicenter , r and omized , double-blind , placebo-controlled study comparing topiramate 100 mg/day and placebo for 26 weeks . The primary efficacy variable was new-onset CDH at month 6 . Secondary efficacy measures included migraine and headache days . Adverse events ( AEs ) were evaluated . Results : A total of 159 topiramate subjects and 171 placebo subjects were efficacy-evaluable . At month 6 , 1.4 % of topiramate subjects versus 2.3 % of placebo subjects had CDH ( p = .589 ) . Compared with placebo , topiramate treatment was associated with statistically significant reductions in mean number of migraine days ( 6.6 vs. 5.3/28 days ; p = .001 ) and headache days ( 6.6 vs 5.3/28 days ; p = .001 ) . Most commonly reported AEs in the topiramate versus placebo group included paresthesia ( 32.4 % vs. 7.0 % ) , fatigue ( 14.8 % vs. 8.6 % ) , dizziness ( 11.4 % vs. 7.6 % ) and nausea ( 10.8 % vs. 9.2 % ) . Conclusion : Topiramate 100 mg/day did not prevent the development of CDH at six months in subjects with HFEM . Topiramate was effective in reducing headache days and migraine headache days and generally well tolerated |
1,648 | 31,952,459 | The results support previous findings that weight-gain occurs quickly . | Introduction : Antipsychotic-induced weight-gain ( AIWG ) is a very important , yet often neglected side-effect in the treatment with first and second generation antipsychotics .
AIWG can increase the risk of developing metabolic syndrome , diabetes and cardiovascular disease .
Meta-analyses mostly concentrate on AIWG in schizophrenic and bipolar patients , even though antipsychotics are prescribed off-label across many other diagnostic groups ( e.g. anxiety disorders , depression , autistic disorder ) . | Objectives To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate ( quetiapine XR ) monotherapy in patients with major depressive disorder ( MDD ) . Patients and methods This was a 10-week ( 8-week active treatment/2-week post-treatment ) r and omized , double-blind , placebo- and active-controlled study ( D1448C00004 ) . Patients received quetiapine XR 150 mg/day , escitalopram 10 mg/day , or placebo ; patients with an inadequate response ( < 20 % improvement in Montgomery – Åsberg Depression Rating Scale [ MADRS ] total score ) at week two received double-dose treatment . The primary end point was week eight change from r and omization in MADRS total score . Secondary end points included MADRS response ( ≥50 % improvement ) and remission ( score ≤8 ) ; Hamilton Rating Scale for Depression total and item 1 ; Hamilton Rating Scale for Anxiety total , psychic , and somatic ; Clinical Global Impressions – Severity of Illness total ; Pittsburgh Sleep Quality Index ( PSQI ) global ; and Quality of Life Enjoyment and Satisfaction Question naire – Short Form percentage maximum total scores . Tolerability was assessed throughout . Results A total of 471 patients was r and omized . No significant improvements in MADRS total score were observed at week eight ( last observation carried forward ) with either active treatment ( quetiapine XR , −17.21 [ P=0.174 ] ; escitalopram , −16.73 [ P=0.346 ] ) versus placebo ( −15.61 ) . There were no significant differences in secondary end points versus placebo , with the exception of week-eight change in PSQI global score ( quetiapine XR , −4.96 [ P<0.01 ] versus placebo , −3.37 ) . Mixed-model repeated- measures analysis of observed-case data suggested that the primary analysis may not be robust . Most commonly reported adverse events included dry mouth , somnolence , and dizziness for quetiapine XR , and headache and nausea for escitalopram . Conclusion In this study , neither quetiapine XR ( 150/300 mg/day ) nor escitalopram ( 10/20 mg/day ) showed significant separation from placebo . Both compounds have been shown previously to be effective in the treatment of MDD ; possible reasons for this failed study are discussed . Quetiapine XR was generally well tolerated , with a profile similar to that reported previously OBJECTIVE The authors evaluated the efficacy and safety of lurasidone in the treatment of patients with major depressive episodes associated with bipolar I disorder . METHOD Patients were r and omly assigned to receive double-blind treatment with lurasidone ( 20 - 60 mg/day [ N=166 ] or 80 - 120 mg/day [ N=169 ] ) or placebo ( N=170 ) for 6 weeks . Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale ( MADRS ) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness ( CGI-BP ) , respectively . RESULTS Lurasidone treatment significantly reduced mean MADRS total scores at week 6 for both the 20 - 60 mg/day group ( -15.4 ; effect size=0.51 ) and the 80 - 120 mg/day group ( -15.4 ; effect size=0.51 ) compared with placebo ( -10.7 ) . Similarly , lurasidone treatment result ed in significantly greater endpoint reduction in CGI-BP depression severity scores for both the 20 - 60 mg/day group ( -1.8 ; effect size=0.61 ) and the 80 - 120 mg/day group ( -1.7 ; effect size=0.50 ) compared with placebo ( -1.1 ) . Both lurasidone groups also experienced significant improvements compared with placebo in anxiety symptoms and in patient-reported measures of quality of life and functional impairment . Discontinuation rates due to adverse events were similar in the 20 - 60 mg/day ( 6.6 % ) , 80 - 120 mg/day ( 5.9 % ) , and placebo ( 6.5 % ) groups . The most frequent adverse events associated with lurasidone were nausea , headache , akathisia , and somnolence . Minimal changes in weight , lipids , and measures of glycemic control were observed with lurasidone . CONCLUSION Monotherapy with lurasidone in the dosage range of 20 - 120 mg/day significantly reduced depressive symptoms in patients with bipolar I depression . Lurasidone was well tolerated , with few changes in weight or metabolic parameters OBJECTIVE To evaluate aripiprazole once-monthly ( AOM ) , a long-acting injectable suspension of aripiprazole , as acute treatment in patients with schizophrenia ( DSM-IV-TR ) . METHOD Adults experiencing an acute psychotic episode were r and omized to 12 weeks of double-blind treatment with AOM 400 mg or placebo ( October 2012-August 2013 ) . The primary efficacy outcome was change from baseline to endpoint ( week 10 ) in Positive and Negative Syndrome Scale ( PANSS ) total score . The key secondary efficacy outcome was change from baseline in Clinical Global Impressions-Severity of Illness scale ( CGI-S ) score . Secondary efficacy outcomes included change from baseline in PANSS positive and negative subscale and Personal and Social Performance Scale ( PSP ) scores . The study took place from October 2012 through August 2013 . RESULTS Patients ( N = 340 ; 79 % male , 66 % black ) were r and omized to AOM ( n = 168 ) or placebo ( n = 172 ) . Least squares ( LS ) mean change from baseline to endpoint ( week 10 ) favored AOM versus placebo in PANSS total ( treatment difference , -15.1 [ 95 % CI , -19.4 to -10.8 ] ; P < .0001 ) and CGI-S ( treatment difference , -0.8 [ 95 % CI , -1.1 to -0.6 ] ; P < .0001 ) scores , as it did at all other timepoints through 12 weeks ( all P ≤ .0005 ) . LS mean change from baseline in PANSS positive and negative subscale and PSP scores favored AOM versus placebo ( P < .0001 ) . Common ( > 10 % ) treatment-emergent adverse events ( AOM vs. placebo ) were increased weight ( 16.8 % vs 7.0 % ) , headache ( 14.4 % vs. 16.3 % ) , and akathisia ( 11.4 % vs 3.5 % ) . CONCLUSIONS Symptoms and functioning improved with AOM 400 mg versus placebo in patients with acute schizophrenia , with acceptable safety and tolerability . These data suggest that AOM 400 mg is a viable treatment option for patients experiencing an acute schizophrenia episode . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01663532 OBJECTIVE The efficacy , safety , and tolerability of brexpiprazole and placebo were compared in adults with acute schizophrenia . METHOD This was a multicenter , r and omized , double-blind , placebo-controlled study . Patients with schizophrenia experiencing an acute exacerbation were r and omly assigned to daily brexpiprazole at a dosage of 0.25 , 2 , or 4 mg or placebo ( 1:2:2:2 ) for 6 weeks . Outcomes included change from baseline to week 6 in Positive and Negative Syndrome Scale ( PANSS ) total score ( primary endpoint measure ) , Clinical Global Impressions Scale ( CGI ) severity score ( key secondary endpoint measure ) , and other efficacy and tolerability measures . RESULTS The baseline overall mean PANSS total score was 95.2 , and the CGI severity score was 4.9 . Study completion rates were 62.2 % , 68.1 % , and 67.2 % for patients in the 0.25- , 2- , and 4-mg brexpiprazole groups , respectively , versus 59.2 % in the placebo group . At week 6 , compared with placebo , brexpiprazole dosages of 2 and 4 mg produced statistically significantly greater reductions in PANSS total score ( treatment differences : -8.72 and -7.64 , respectively ) and CGI severity score ( treatment differences : -0.33 and -0.38 ) . The most common treatment-emergent adverse event for brexpiprazole was akathisia ( 2 mg : 4.4 % ; 4 mg : 7.2 % ; placebo : 2.2 % ) . Weight gain with brexpiprazole was moderate ( 1.45 and 1.28 kg for 2 and 4 mg , respectively , versus 0.42 kg for placebo at week 6 ) . There were no clinical ly or statistically significant changes from baseline in lipid and glucose levels and extrapyramidal symptom ratings . CONCLUSIONS Brexpiprazole at dosages of 2 and 4 mg/day demonstrated statistically significant efficacy compared with placebo and good tolerability for patients with an acute schizophrenia exacerbation The aim of this study was to evaluate the short-term efficacy and safety of lurasidone in treating irritability associated with autistic disorder . In this multicenter trial , out patients age 6–17 years who met DSM-IV-TR criteria for autistic disorder , and who demonstrated irritability , agitation , and /or self-injurious behaviors were r and omized to 6 weeks of double-blind treatment with lurasidone 20 mg/day ( N = 50 ) , 60 mg/day ( N = 49 ) , or placebo ( N = 51 ) . Efficacy measures included the Aberrant Behavior Checklist Irritability subscale ( ABC-I , the primary endpoint ) and the Clinical Global Impressions , Improvement ( CGI-I ) scale , and were analyzed using a likelihood-based mixed model for repeated measures . Least squares ( LS ) mean ( st and ard error [ SE ] ) improvement from baseline to Week 6 in the ABC-I was not significantly different for lurasidone 20 mg/day ( −8.8 [ 1.5 ] ) and lurasidone 60 mg/day ( −9.4 [ 1.4 ] ) versus placebo ( −7.5 [ 1.5 ] ; p = 0.55 and 0.36 , respectively ) . CGI-I scores showed significantly greater LS mean [ SE ] improvement at Week 6 for lurasidone 20 mg/day versus placebo ( 2.8 [ 0.2 ] vs. 3.4 [ 0.2 ] ; p = 0.035 ) but not for lurasidone 60 mg/day ( 3.1 [ 0.2 ] ; p = 0.27 ) . Discontinuation rates due to adverse events were : lurasidone 20 mg/day , 4.1 % ; 60 mg/day , 3.9 % ; and placebo , 8.2 % . Adverse events with an incidence ≥10 % ( lurasidone combined , placebo ) included vomiting ( 18.0 , 4.1 % ) and somnolence ( 12.0 , 4.1 % ) . Modest changes were observed in weight and selected metabolic parameters . In this study , once-daily , fixed doses of 20 and 60 mg/day of lurasidone were not demonstrated to be efficacious compared to placebo for the short-term treatment of children and adolescents with moderate-to-severe irritability associated with autistic disorder AIMS Morbidity and mortality from drug overdose has decreased over three decades . This is credited to safer drugs and therefore better outcomes in overdose . We aim ed to investigate changing prescriptions of antipsychotic medications and associated changes in antipsychotic overdoses over a 26-year period . METHODS All antipsychotic poisoning presentations to a tertiary referral toxicology unit between 1987 and 2012 were review ed . Data were collected prospect ively on demographics , ingestion information , clinical effects , complications and treatment . Rates of antipsychotic drug use in Australia were obtained from Australian government publications for 1990 - 2011 and linked to overdose admissions by postcode . RESULTS There were 3180 antipsychotic overdoses : 1235 first generation antipsychotics , 1695 ' atypical ' second generation antipsychotics and 250 lithium overdoses . Over 26 years , antipsychotic overdoses increased 1.8-fold , with first generation antipsychotics decreasing to one-fifth of their peak ( ≈80/year to 16 ) and second generation antipsychotics increasing to double this ( ≈160/year ) , olanzapine and quetiapine accounting for 78 % . All antipsychotic overdoses had a median length of stay of 18.6 h , 15.7 % admitted to intensive care unit , 10.4 % ventilated and 0.13 % died in hospital , which was the same for first generation compared to second generation antipsychotics . There was a 2.3-fold increase in antipsychotic prescriptions over the same period ; first generation antipsychotics declined whereas there was a dramatic rise in second generation antipsychotics , mainly olanzapine , quetiapine and risperidone ( 79 % ) . CONCLUSION Over 26 years there was an increase in antipsychotic prescribing associated with an increase in antipsychotic overdoses . Although the type of antipsychotics changed , the morbidity and mortality remained the same , so that antipsychotics are an increasing proportion of overdose admissions OBJECTIVE To assess the effect of dose increase in adult patients with schizophrenia who demonstrate inadequate initial response to st and ard-dose lurasidone and to evaluate the efficacy of low-dose lurasidone in adult patients with schizophrenia . METHODS In this r and omized , double-blind , placebo-controlled study conducted between May 2013 and June 2014 , hospitalized patients with acute schizophrenia ( DSM-IV-TR criteria ) were r and omly assigned to double-blind treatment with lurasidone 20 mg/d ( n = 101 ) , lurasidone 80 mg/d ( n = 199 ) , or placebo ( n = 112 ) . Nonresponders to lurasidone 80 mg/d ( Positive and Negative Syndrome Scale [ PANSS ] score decrease < 20 % ) at 2 weeks were re-r and omized to lurasidone 80 mg/d or 160 mg/d for the remaining 4 weeks of the study . The primary outcome measure was change from baseline to week 6 in PANSS total score . RESULTS In nonresponders to lurasidone 80 mg/d ( n = 95 ) , dose increase to 160 mg/d at week 2 significantly reduced PANSS total score at week 6 study endpoint compared with continuing 80 mg/d ( -16.6 vs -8.9 ; P < .05 [ effect size = 0.52 ] ) . While a comparable magnitude of improvement was observed in Clinical Global Impression-Severity ( CGI-S ) score from week 2 to week 6 endpoint for lurasidone 160 mg/d versus 80 mg/d ( -1.0 vs -0.6 ; effect size = 0.44 ) , the difference was not statistically significant ( P = .052 ) . Patients receiving lurasidone 20 mg/d did not demonstrate significant improvement compared with placebo at week 6 in PANSS total ( -17.6 vs -14.5 ; P = .26 ) or CGI-S ( -0.93 vs -0.73 ; P = .17 ) scores . Few dose-related adverse effects associated with lurasidone were observed . CONCLUSIONS In adult patients with schizophrenia demonstrating nonresponse to 2 weeks of treatment with lurasidone 80 mg/d , dose increase to 160 mg/d result ed in significant symptom improvement compared with continuing lurasidone 80 mg/d . Lurasidone 20 mg/d was not associated with significant improvement in psychotic symptoms in adult patients with schizophrenia . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01821378 Rationale Asenapine is a second generation anti-psychotic approved in the USA in 2009 for the treatment of schizophrenia , but its efficacy has not been proven in Asian patients . Objectives The objectives of this study are to evaluate the efficacy and tolerability of asenapine in Asian patients experiencing an acute exacerbation of schizophrenia . Methods In this prospect i ve , double-blind study , patients in Japan , Korea , and Taiwan were r and omized ( 1:1:1 ) to asenapine 5 mg twice daily ( bid ) , 10 mg bid or placebo for 6 weeks after a 3- to 7-day washout/screening period . The primary endpoint was the mean change in the positive and negative syndrome scale ( PANSS ) total score from baseline to day 42/treatment end . Results Of the 532 participants r and omized , 530 received treatment . The primary endpoint was significantly greater with asenapine 5 and 10 mg bid than with placebo ( −12.24 and −14.17 vs. −0.95 ; p < 0.0001 ) . The results of secondary endpoints including PANSS negative subscale scores and PANSS responders at the end of treatment supported the results of the primary endpoint . There were no significant differences in the incidence of treatment-emergent adverse events reported with asenapine 5 and 10 mg bid and placebo ( 84.6 , 80.7 , and 81.6 % ) . There was a mean ( ± st and ard deviation ) change in weight of −1.76 ± 2.45 kg for placebo , + 0.42 ± 2.65 kg for asenapine 5 mg bid , and + 0.81 ± 2.89 kg for asenapine 10 mg bid group . Conclusions Asenapine was effective and generally well tolerated when used for the treatment of acute exacerbations of schizophrenia in Asian patients Objective The aim of this analysis was to compare the effects of 2 atypical antipsychotic agents , lurasidone ( 80 mg/d or 160 mg/d ) and quetiapine XR ( 600 mg/d ) , on daytime alertness , and to evaluate the effects of daytime sleepiness on treatment outcomes in patients with an acute exacerbation of schizophrenia . Methods Patients who met Diagnostic and Statistical Manual of Mental Disorders , 4th edition , text revision ( DSM-IV-TR ) criteria for schizophrenia were r and omized to 6 weeks of double-blind treatment with fixed doses of lurasidone 80 mg/d ( n = 125 ) , lurasidone 160 mg/d ( n = 121 ) , quetiapine XR 600 mg/d ( n = 119 ) , or placebo ( n = 121 ) , all dosed once daily in the evening , with food . Daytime sleepiness was assessed using the Epworth Sleepiness Scale ( ESS ) . Results Daytime sleepiness improved in the lurasidone and placebo-treated groups but worsened in the quetiapine XR treatment group when compared to placebo ( p = 0.001 ) and to either dose of lurasidone ( both p < 0.01 ) . Sedation associated with quetiapine XR treatment mediated an improvement in agitation [ assessed by the Positive and Negative Syndrome Scale — Excitement ( PANSS-EC ) subscale ] and a worsening in functional capacity [ assessed by the University of California – San Diego ( UCSD ) Performance-Based Skills Assessment —Brief Version ( UPSA-B ) total score ] ; these mediating relationships were not observed for the lurasidone or placebo treatment groups . Conclusion In this 6-week double-blind study , treatment with lurasidone 80 mg or 160 mg , administered once daily in the evening , was associated with a reduction in daytime sleepiness similar in magnitude to placebo , while quetiapine XR 600 mg/d was associated with a significant increase in daytime sleepiness , compared to both lurasidone dose groups and placebo . Daytime sleepiness was associated with improvement in agitation and worsening in functional capacity for quetiapine XR , but not lurasidone or placebo-treated patients Abstract Objective : To evaluate the efficacy and safety of lurasidone in acutely symptomatic adolescent patients with schizophrenia . Methods : Patients aged 13–17 years were r and omly assigned to 6 weeks of double-blind , fixed-dose lurasidone ( 40 or 80 mg/day ) or placebo . Primary and key secondary efficacy measures were change from baseline to week 6 in the Positive and Negative Symptom Scale ( PANSS ) total score and Clinical Global Impressions-Severity ( CGI-S ) score , respectively , using mixed model for repeated measurement ( MMRM ) analysis . The proportion of patients achieving treatment response at endpoint , based on ≥20 % reduction in PANSS total score , was analyzed using a logistic regression model . Results : Least-squares ( LS ) mean change in PANSS total score from baseline to week 6 was −18.6 with lurasidone 40 mg/day ( N = 108 ; p < 0.001 vs. placebo ; effect size = 0.51 ) , −18.3 with lurasidone 80 mg/day ( N = 106 ; p < 0.001 vs. placebo ; effect size = 0.48 ) , and −10.5 with placebo ( N = 112 ) . Similarly , LS mean change in CGI-S score from baseline to week 6 was significantly greater with lurasidone 40 mg/day ( −1.0 ; p < 0.001 ; effect size = 0.49 ) and 80 mg/day ( −0.9 ; p = 0.0015 ; effect size = 0.45 ) compared with placebo ( −0.5 ) . A significantly higher proportion of patients met responder criteria on lurasidone 40 and 80 mg/day versus placebo ( 63.9 % and 65.1 % vs. 42.0 % ; p < 0.001 for both comparisons ) . The rate of study discontinuation was 10.3 % in lurasidone-treated and 17.7 % in placebo-treated patients . The most common adverse events ( incidence ≥5 % in either lurasidone dose group and at least twice the rate of placebo ) for lurasidone 40 mg/day , 80 mg/day , and placebo , respectively , were nausea ( 12.7 % , 14.4 % , and 2.7 % ) , somnolence ( 9.1 % , 11.5 % , and 5.4 % ) , akathisia ( 9.1 % , 8.7 % , and 1.8 % ) , vomiting ( 8.2 % , 6.7 % , and 1.8 % ) , and sedation ( 5.5 % , 1.9 % , and 1.8 % ) . Treatment with lurasidone was not associated with clinical ly meaningful effects on body weight , lipids , measures of glycemic control , or prolactin . Conclusions : In this 6-week study , lurasidone at doses of 40 and 80 mg/day demonstrated statistically significant and clinical ly meaningful symptom improvement in adolescent patients with schizophrenia . Lurasidone was generally well tolerated with few effects on weight and metabolic parameters , consistent with findings in adult patients with schizophrenia Background Depression in bipolar I disorder responds to the atypical antipsychotic olanzapine . This sub population analysis assessed whether olanzapine is superior to placebo specifically in the treatment of Chinese patients with bipolar I depression . Methods This was a sub population analysis of a 6-week , multicenter , double-blind , parallel , r and omized , placebo-controlled trial among 12 Chinese study centers . Eligible in patients and out patients were r and omized to olanzapine ( 5 to 20 mg/day ) or placebo . Patients were primarily assessed by the Montgomery-Åsberg Depression Rating Scale total score . Secondary assessment s used a range of other efficacy and safety measures . This sub population analysis was underpowered to show statistically significant differences between treatment groups . Results In total , 210 patients ( mean age 32.9 years at baseline , 54.3 % females ) were r and om-ized . Similar proportions of patients treated with olanzapine ( 75.0 % ) and placebo ( 72.9 % ) completed the double-blind phase . Baseline-to-endpoint least-squares mean ± st and ard error decrease in the Montgomery-Åsberg Depression Rating Scale total score in the olanzapine group ( −13.55±0.80 ) was similar to that noted in the parent trial ( −13.82±0.65 ) . However , the difference between olanzapine and placebo groups was not statistically significant ( P=0.44 ) ; this finding was also true for the secondary efficacy measures . A post hoc analysis showed a greater emergence of mania in the placebo group , which likely reduced the treatment difference between olanzapine and placebo in the primary efficacy measure . Safety data were consistent with the known safety profile of olanzapine , including a higher incidence of weight gain ( ≥7 % ) in the olanzapine group ( 24.1 % vs 1.4 % , P<0.001 ) . Conclusion Olanzapine provides similar improvement in depression among Chinese and non-Chinese bipolar I patients . The lack of a statistically significant difference between the olanzapine and placebo groups in this Chinese sub population analysis may relate to an a priori lack of study power , and underestimation of the effect of olanzapine because of a greater emergence of mania in placebo-treated patients and missing data associated with a high early discontinuation rate OBJECTIVE This study evaluated the efficacy , safety , and tolerability of aripiprazole lauroxil , a novel long-acting injectable atypical antipsychotic , for the treatment of schizophrenia . METHOD An international multicenter , r and omized , double-blind , placebo-controlled trial was conducted between December 2011 and March 2014 . Patients ( N = 623 ) aged 18 to 70 years with schizophrenia ( DSM-IV-TR criteria ) , experiencing an acute exacerbation , were r and omized in a 1:1:1 ratio to receive gluteal intramuscular injection of aripiprazole lauroxil 441 mg , aripiprazole lauroxil 882 mg , or matching placebo once monthly for 12 weeks . The primary efficacy outcome was change in Positive and Negative Syndrome Scale ( PANSS ) total score from baseline to day 85 . The Clinical Global Impressions-Improvement scale ( CGI-I ) score at day 85 was the secondary efficacy outcome . Safety and tolerability were assessed . RESULTS The PANSS total score ( mean ± st and ard error [ SE ] ) improved significantly from baseline to day 85 in the aripiprazole lauroxil 441 mg and 882 mg groups , with placebo-adjusted differences of -10.9 ± 1.8 ( P < .001 ) and -11.9 ± 1.8 ( P < .001 ) , respectively . Significant ( P ≤ .004 ) improvements in both active treatment groups were demonstrated as early as day 8 and continued throughout the treatment period . The proportion of patients who were very much or much improved on the CGI-I was significantly greater with aripiprazole lauroxil 441 mg and 882 mg treatment versus placebo ( P < .001 ) . The most common treatment-emergent adverse events were insomnia , akathisia , headache , and anxiety . The incidence of injection site reactions was low , predominantly described as injection site pain , and was associated with the first injection . CONCLUSIONS Aripiprazole lauroxil demonstrated robust efficacy for treatment of patients experiencing acute exacerbation of schizophrenia . The improvement in psychotic symptoms was statistically significant and clinical ly meaningful . Symptom improvement occurred rapidly after initiation of aripiprazole lauroxil treatment and was maintained throughout the study . Both aripiprazole lauroxil 441 mg and 882 mg doses were well tolerated . These results support aripiprazole lauroxil as an important new treatment option for schizophrenia . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01469039 ; Clinical trialsregister.eu identifier : 2012 - 003445 - 15 Abstract Objectives . To investigate the efficacy and safety of aripiprazole in Asian patients with manic or mixed episodes associated with bipolar I disorder . Methods . Subjects were r and omised to aripiprazole ( 24 mg/day ; reduced to 12 mg/day if needed for tolerability ; n = 128 ) or placebo ( n = 130 ) for 3 weeks in this multicentre , double-blind study . The primary efficacy measure was mean change from baseline in Young Mania Rating Scale ( YMRS ) Total score . Results . A total of 136 patients ( aripiprazole 56.3 % ; placebo 49.2 % ) completed the study . The majority of patients ( 92.6 % ) received aripiprazole 24 mg/day . Aripiprazole produced statistically significant mean improvements in YMRS Total scores compared with placebo from Day 4 through to Week 3 ( –11.3 vs. –5.3 ; P < 0.001 ) . The most common adverse events ( > 15 % of patients ; aripiprazole vs. placebo ) were akathisia ( 22.0 vs. 5.6 % ) and insomnia ( 16.3 vs. 9.6 % ) . Aripiprazole treatment result ed in no significant difference from placebo in change in mean body weight from baseline ( –0.4 vs. –0.7 kg ; P = 0.231 ) . Aripiprazole was not associated with an elevated serum prolactin level . Conclusions . Aripiprazole had significantly greater efficacy than placebo for the treatment of acute manic or mixed episodes associated with bipolar I disorder in Asian patients . Treatment was generally safe and well tolerated OBJECTIVE Quetiapine is an atypical antipsychotic with demonstrated efficacy in the treatment of adolescent schizophrenia and pediatric bipolar mania . Large , placebo-controlled studies of interventions in pediatric bipolar depression are lacking . The current study investigated the efficacy and safety of quetiapine extended-release ( XR ) in patients 10 - 17 years of age , with acute bipolar depression . METHODS This multicenter , double-blind , r and omized , placebo-controlled study investigated quetiapine XR ( dose range , 150 - 300 mg/day ) in pediatric out patients with an American Psychiatric Association , Diagnostic and Statistical Manual of Mental Disorders , 4th ed . , Text Revision ( DSM-IV-TR ) diagnosis of bipolar I or bipolar II disorder ( current or most recent episode depressed ) treated for up to 8 weeks ( Clinical Trials.gov identifier : NCT00811473 ) . The primary study outcome was mean change in Children 's Depression Rating Scale-Revised ( CDRS-R ) total score . Secondary efficacy outcomes included CDRS-R-based response and remission rates . RESULTS Of 193 patients r and omized to treatment , 144 patients completed the study ( 75.3 % of quetiapine XR group [ n=70 ] ; 74.0 % of placebo group [ n=74 ] ) . Least squares mean changes in CDRS-R total score at week 8 were : -29.6 ( SE , 1.65 ) with quetiapine XR and -27.3 ( SE , 1.60 ) with placebo , a between-treatment group difference of -2.29 ( SE , 1.99 ; 95 % CI , -6.22 , 1.65 ; p=0.25 ; mixed-model for repeated measures analysis ) . Rates of response and remission did not differ significantly between treatment groups . The safety profile of quetiapine XR was broadly consistent with the profile reported previously in adult studies of quetiapine XR and pediatric studies of quetiapine immediate-release ( IR ) . Potentially clinical ly significant elevations in clinical chemistry values included triglycerides ( 9.3 % , quetiapine XR ; 1.4 % , placebo group ) and thyroid stimulating hormone ( 4.7 % , quetiapine XR ; 0 % , placebo group ) . An adverse event potentially related to diabetes mellitus occurred in 3.3 % of the quetiapine XR versus no adverse events in the placebo group . CONCLUSIONS Quetiapine XR did not demonstrate efficacy relative to placebo in this 8 week study of pediatric bipolar depression . Quetiapine XR was generally safe and well tolerated Rationale Quetiapine extended release ( XR ) has been used to treat various psychiatric disorders , including depressive episodes associated with bipolar I and II disorders . Quetiapine XR is the first approved drug in China for the treatment of bipolar disorder . Objectives The study evaluated the efficacy and safety of short-term quetiapine XR monotherapy in the treatment of depressive episodes of bipolar I and II disorders . Methods This was an 8-week multi-center , r and omized , double-blind , placebo-controlled , fixed-dose phase 3 study . The primary endpoint was the mean change of the Montgomery-Åsberg Depression Rating Scale ( MADRS ) total score . Secondary endpoints included Clinical Global Impressions-Bipolar ( CGI-BP ) and remission rates . Results The study recruited 279 adult bipolar I or II patients currently experiencing depression from 11 Chinese provinces . Of these , 139 received quetiapine XR ( 300 mg/day ) and 140 received placebo for 8 weeks . The mean change in the MADRS total score was significantly greater in the quetiapine XR group than in the placebo group ( −19.00 ± 7.88 vs. −16.20 ± 9.32 ; p = 0.004 ) . Adverse events occurred in 96 patients ( 65.3 % ) in the quetiapine XR group and 72 ( 49.0 % ) in the placebo group . The incidence of serious adverse events did not differ significantly between the groups ( p = 0.247 ) . Conclusions This study , which is the first to evaluate 300 mg/day quetiapine XR monotherapy for depression in Chinese patients with bipolar disorders , found that this drug was superior to the placebo . Quetiapine XR was generally safe and well tolerated ( Clinical Trials.gov number , NCT01256177 ) OBJECTIVE This phase 3 study evaluated the efficacy , safety , and tolerability of cariprazine in patients with acute exacerbation of schizophrenia . METHOD This multinational , r and omized , double-blind , placebo- and active-controlled study was conducted from April 2010 to December 2011 . Patients who met DSM-IV-TR criteria for schizophrenia were r and omized to placebo ( n = 153 ) , cariprazine 3 mg/d ( n = 155 ) , cariprazine 6 mg/d ( n = 157 ) , or aripiprazole 10 mg/d ( n = 152 ) for 6 weeks of double-blind treatment . The primary and secondary efficacy parameters were mean change from baseline to week 6 in Positive and Negative Syndrome Scale ( PANSS ) total score and Clinical Global Impressions-Severity of Illness ( CGI-S ) score , respectively . RESULTS Least squares mean differences ( LSMDs ) in PANSS total score change at week 6 significantly favored cariprazine 3 and 6 mg/d versus placebo ( LSMD [ 95 % CI ] : 3 mg/d , -6.0 [ -10.1 to -1.9 ] , adjusted P = .0044 ; 6 mg/d , -8.8 [ -12.9 to -4.7 ] , adjusted P < .0001 ) . Cariprazine 3 and 6 mg/d were also associated with significant improvements relative to placebo in CGI-S scores ( LSMD [ 95 % CI ] : 3 mg/d , -0.4 [ -0.6 to -0.2 ] , adjusted P = .0044 ; 6 mg/d , -0.5 [ -0.7 to -0.3 ] , adjusted P < .0001 ) . Significant differences from placebo were also observed with aripiprazole on the PANSS ( LSMD [ 95 % CI ] : -7.0 [ -11.0 to -2.9 ] , P = .0008 ) and CGI-S ( LSMD [ 95 % CI ] : -0.4 [ -0.6 to -0.2 ] , P = .0001 ) . Common treatment-emergent adverse events ( ≥ 10 % ) were insomnia ( all groups ) , akathisia ( cariprazine 6 mg/d ) , and headache ( placebo , cariprazine 6 mg/d ) . CONCLUSIONS This study supports the efficacy , safety , and tolerability of cariprazine 3 and 6 mg/d in the treatment of patients with acute exacerbation of schizophrenia . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01104766 INTRODUCTION Cariprazine is an orally active and potent D3 and D2 partial agonist with preferential binding to D3 receptors in development for the treatment of schizophrenia and bipolar mania . This study ( NCT00694707 ) evaluated the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia . METHODS This study was a multinational , double-blind , r and omized , placebo- and active-controlled , fixed-dose trial . Patients were r and omized to receive placebo , cariprazine 1.5mg/d , cariprazine 3.0mg/d , cariprazine 4.5mg/d , or risperidone 4.0mg/d ( for assay sensitivity ) for 6 weeks of double-blind treatment and 2 weeks of safety follow-up . Primary and secondary efficacy parameters were change from baseline to Week 6 in Positive and Negative Syndrome Scale ( PANSS ) total and Global Impressions-Severity of Illness ( CGI-S ) scores , respectively . Safety parameters included adverse events ( AEs ) , vital signs , laboratory measures , and extrapyramidal symptom ( EPS ) scales . RESULTS Of 732 r and omized patients , 64 % completed the study . PANSS total score improvement at Week 6 was statistically significant versus placebo for cariprazine 1.5mg/d , 3.0mg/d , and 4.5mg/d ( least squares mean difference [ LSMD ] : -7.6 , -8.8 , -10.4 , respectively ; p<0.001 ; LOCF ) and risperidone ( -15.1 , p<0.001 ; LOCF ) ; significant improvement on CGI-S was demonstrated for all active treatments ( p<0.05 ) . The most frequent cariprazine AEs ( ≥ 5 % and at least twice the rate of the placebo group ) were insomnia , extrapyramidal disorder , akathisia , sedation , nausea , dizziness , and constipation . Mean changes in metabolic parameters were small and similar between groups . CONCLUSION The results of this study support the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia UNLABELLED Vabicaserin , a potent 5-HT2C receptor agonist , decreases nucleus accumbens extracellular dopamine levels in rats , without affecting striatal dopamine , indicating mesolimbic selectivity . This is the first study of efficacy , safety and tolerability of vabicaserin in adults with acute schizophrenia . Three hundred fourteen hospitalized subjects were r and omized to : Vabicaserin 200 or 400 mg/day , olanzapine 15 mg/day or placebo . Central raters assessed the PANSS and CGI-S. Site raters performed the BPRS and CGI-I. Central rated PANSS Positive ( PANSS-PPS ) was the primary endpoint . Two hundred eighty-nine subjects were included in the mITT efficacy analysis . Vabicaserin was well tolerated with no major safety concerns . Olanzapine , but not vabicaserin , caused weight gain . Vabicaserin 200 mg/day and olanzapine demonstrated significant improvement at week 6 vs. placebo on PANSS-PSS . A non-significant decrease vs. placebo was observed for 400 mg/day . Both vabicaserin groups demonstrated significant improvement over baseline on PANSS Negative while placebo worsened . Vabicaserin 200 mg/day and olanzapine demonstrated significantly greater improvement over placebo on PANSS Total whereas 400 mg/day showed a trend toward improvement . There was no significant improvement vs. placebo for either vabicaserin group on site-rated BPRS . Vabicaserin 200 mg/day and olanzapine demonstrated significant improvement vs. placebo on CGI-I and CGI-S but not 400 mg/day vabicaserin . Vabicaserin demonstrated efficacy on primary and secondary endpoints at 200 mg/day , but not at 400 mg/day which showed a trend for efficacy . The 200 mg/day vabicaserin group achieved proof of concept using central ratings . Both vabicaserin doses were well tolerated with no significant safety signals and no weight gain . TRIAL REGISTRATION clinical trials.gov . Identifier : NCT00265551 BACKGROUND Available data on atypical antipsychotic-induced weight gain are limited by a number of method ological factors . The objective of this report is to evaluate short-term ( N=1742 ) and long-term ( N=1649 ) weight effects in patients receiving st and ard doses of amisulpride , haloperidol , olanzapine , risperidone , ziprasidone , and placebo based on 21 r and omized , placebo-controlled , parallel-group studies from an integrated clinical trial data base . METHOD Analyses of the integrated ziprasidone schizophrenia trials data base were performed to estimate the weighted average of weight change and the percentage of subjects experiencing weight gain ( or weight loss ) across studies for each agent studied , based on fixed- and r and om-effects models . Duration s of treatment exposure in long-term trials were controlled by well-defined time windows ( 6 month : 150 to 210 days ; 1 year : 330 to 390 days ) . Weight gain or loss was defined using a 7 % change from baseline threshold . RESULTS During long-term therapy with 1-year treatment duration , incidence of weight gain for subjects treated with ziprasidone ( 17 % ) was not significantly different from the placebo ( 13 % ) or haloperidol ( 41 % ) groups based on 95 % confidence interval . In contrast , significantly greater weight gain incidence was observed for the olanzapine ( 57 % ) and risperidone ( 39 % ) groups compared to placebo . Median weight change of + 0.49 , -0.18 , + 1.50 and + 0.55 lb/month was observed for haloperidol , ziprasidone , olanzapine and risperidone subjects , respectively , indicating differential weight change patterns compared to placebo ( -0.32 ) . Similar results were observed for the short-term ( 4 - 12 weeks ) and 6-month treatment exposure cohorts . CONCLUSIONS Our results confirm significant differences in long-term weight effects among atypical antipsychotics , consistent with findings from prior meta- analysis of antipsychotic-induced weight gain [ Allison , D.B. , Mentore , J.L. , Heo , M. , Ch and ler , L.P. , Capelleri , J.C. , Infante , M.C. , Weiden , P.J. , 1999 . Antipsychotic induced weight gain : a comprehensive research synthesis . Am J Psychiatry 156 , 1686 - 1696 ] and the CATIE schizophrenia study [ Lieberman , J.A. , Stroup , T.S. , McEvoy , J.P. , et al. , 2005 . Effectiveness of antipsychotic drugs in patients with chronic schizophrenia . N Engl J Med 353 , 1209 - 1223 ] OBJECTIVE To evaluate the efficacy and safety of lurasidone in children and adolescents with bipolar depression . METHOD Patients 10 to 17 years old with a DSM-5 diagnosis of bipolar I depression were r and omized to 6 weeks of double-blind treatment with flexible doses of lurasidone 20 to 80 mg/day . The primary endpoint was change from baseline to week 6 in the Children 's Depression Rating Scale-Revised ( CDRS-R ) total score , evaluated by a mixed-model repeated- measures analysis . RESULTS A total of 347 patients were r and omized and received at least 1 dose of lurasidone ( n = 175 ; mean age 14.2 years ; mean dose 33.6 mg/day ) or placebo ( n = 172 ; mean age 14.3 years ) . At week 6 , treatment with lurasidone was associated with statistically significant improvement compared with placebo in CDRS-R total score ( -21.0 versus -15.3 ; p < .0001 ; effect size 0.45 ) . Lurasidone also was associated with statistically significant improvement in the Clinical Global Impression-Bipolar Severity depression score ( key secondary measure ) and in measures of anxiety , quality of life , and global functioning . Study completion rates were 92.0 % in the lurasidone group and 89.7 % in the placebo group ; discontinuation rates due to adverse events were the same for the 2 groups ( 1.7 % ) . The 2 most common adverse events on lurasidone were nausea and somnolence . Treatment with lurasidone was associated with few effects on weight and metabolic parameters . CONCLUSION In this placebo-controlled study , monotherapy with lurasidone , in the dose range of 20 to 80 mg/day , significantly decreased depressive symptoms in children and adolescents with bipolar depression . Lurasidone was well tolerated , with minimal effects on weight and metabolic parameters . Clinical trial registration information-Lurasidone Pediatric Bipolar Study ; http:// Clinical trials.gov ; NCT02046369 OBJECTIVE Accumulating evidence indicates that manic symptoms below the threshold for hypomania ( mixed features ) are common in individuals with major depressive disorder . This form of depression is often severe and is associated with an increased risk for recurrence , suicide attempts , substance abuse , and functional disability . This study evaluated the efficacy and safety of lurasidone in major depressive disorder with mixed features . METHODS Patients meeting DSM-IV-TR criteria for major depressive disorder who presented with two or three protocol -defined manic symptoms were r and omly assigned to 6 weeks of double-blind treatment with either lurasidone at 20 - 60 mg/day ( N=109 ) or placebo ( N=100 ) . Changes from baseline in Montgomery-Åsberg Depression Rating Scale score ( MADRS ; primary outcome measure ) and Clinical Global Impressions severity subscale score ( CGI-S ; key secondary outcome measure ) were evaluated using a mixed model for repeated- measures analysis . RESULTS Lurasidone significantly improved depressive symptoms and overall illness severity , assessed by least squares mean change at week 6 in the MADRS and CGI-S scores : -20.5 compared with -13.0 ( effect size , 0.80 ) and -1.8 compared with -1.2 ( effect size , 0.60 ) , respectively . Significant improvement in manic symptoms , assessed by the Young Mania Rating Scale , was also observed , in addition to other secondary efficacy endpoints . Rates of discontinuation due to adverse events were low . The most common adverse events were nausea ( 6.4 % and 2.0 % in the lurasidone and placebo groups , respectively ) and somnolence ( 5.5 % and 1.0 % ) . CONCLUSIONS Lurasidone was effective and well tolerated in this study involving patients with major depressive disorder associated with subthreshold hypomanic symptoms ( mixed features ) AIM This study aim ed to evaluate the efficacy , safety , and tolerability of brexpiprazole compared to placebo in Japanese patients with acute schizophrenia ( SCZ ) . METHODS We conducted a 6-week , multicenter , double-blind , placebo-controlled , phase 2/3 study in Japan . Patients with acute SCZ were r and omized ( 1:1:1:1 ) to receive brexpiprazole 1 mg , 2 mg , 4 mg , or placebo once a day . The primary endpoint was the change from baseline to week 6 in Positive and Negative Syndrome Scale ( PANSS ) total scores . RESULTS In the 459 patients that were r and omized , brexpiprazole 2 mg showed a significant improvement versus placebo ( treatment difference : -7.32 , P = 0.0124 ) , although brexpiprazole 4 mg showed numerical improvements ( treatment difference : -3.86 , P = 0.1959 ) , and brexpiprazole 1 mg showed only minimal change ( treatment difference : -0.63 , P = 0.8330 ) . Treatment-emergent adverse events with an incidence of ≥5 % and ≥2 times the rate of placebo in the brexpiprazole groups were vomiting , elevated blood prolactin , diarrhea , nausea , and dental caries . Most treatment-emergent adverse events were mild or moderate in severity . There were no clinical ly significant changes in electrocardiogram parameters , bodyweight , laboratory values , or vital signs in the brexpiprazole groups . CONCLUSION Brexpiprazole was efficacious and well tolerated in Japanese adult patients with acute SCZ The objective of this study was to evaluate the efficacy , safety and tolerability of brexpiprazole versus placebo in adults with acute schizophrenia . This was a 6-week , multicenter , placebo-controlled double-blind phase 3 study . Patients with acute schizophrenia were r and omized to brexpiprazole 1 , 2 or 4 mg , or placebo ( 2:3:3:3 ) once daily . The primary endpoint was changed from baseline at week 6 in Positive and Negative Syndrome Scale ( PANSS ) total score ; the key secondary endpoint was Clinical Global Impressions-Severity ( CGI-S ) at week 6 . Brexpiprazole 4 mg showed statistically significant improvement versus placebo ( treatment difference : -6.47 , p=0.0022 ) for the primary endpoint . Improvement compared with placebo was also seen for the key secondary endpoint ( treatment difference : -0.38 , p=0.0015 ) , and on multiple secondary efficacy outcomes . Brexpiprazole 1 and 2 mg also showed numerical improvements versus placebo , although p>0.05 . The most common treatment-emergent adverse events were headache , insomnia and agitation ; incidences of akathisia were lower in the brexpiprazole treatment groups ( 4.2%-6.5 % ) versus placebo ( 7.1 % ) . Brexpiprazole treatment was associated with moderate weight gain at week 6 ( 1.23 - 1.89 kg versus 0.35 kg for placebo ) ; there were no clinical ly relevant changes in laboratory parameters and vital signs . In conclusion , brexpiprazole 4 mg is an efficacious and well-tolerated treatment for acute schizophrenia in adults . Clinical Trials.gov NCT01393613 ; BEACON trial OBJECTIVE This phase 3 trial evaluated the efficacy , safety , and tolerability of low- and high-dose cariprazine in patients meeting DSM-IV-TR criteria for acute manic or mixed episodes associated with bipolar I disorder . METHOD This multicenter , r and omized , double-blind , placebo-controlled , parallel-group , fixed/flexible-dose study was conducted from February 2010 to December 2011 . Patients were r and omly assigned to placebo , cariprazine 3 - 6 mg/d , or cariprazine 6 - 12 mg/d for 3 weeks of double-blind treatment . Primary and secondary efficacy parameters were change from baseline to week 3 in Young Mania Rating Scale ( YMRS ) total score and Clinical Global Impressions-Severity of Illness ( CGI-S ) score , respectively . Post hoc analysis examined change from baseline to week 3 in YMRS single items . RESULTS A total of 497 patients were r and omized ; 74 % completed the study . The least squares mean difference ( LSMD ) for change from baseline to week 3 in YMRS total score was statistically significant in favor of both cariprazine groups versus placebo ( LSMD [ 95 % CI ] : 3 - 6 mg/d , -6.1 [ -8.4 to -3.8 ] ; 6 - 12 mg/d , -5.9 [ -8.2 , -3.6 ] ; P < .001 [ both ] ) . Both cariprazine treatment groups showed statistically significant superiority to placebo on all 11 YMRS single items ( all comparisons , P < .05 ) . Change from baseline in CGI-S scores was statistically significantly greater in both cariprazine groups compared with placebo ( LSMD [ 95 % CI ] : 3 - 6 mg/d , -0.6 [ -0.9 to -0.4 ] ; 6 - 12 mg/d , -0.6 [ -0.9 to -0.3 ] ; P < .001 [ both ] ) . The most common ( ≥ 5 % and twice the rate of placebo ) treatment-related adverse events for cariprazine were akathisia ( both groups ) and nausea , constipation , and tremor ( 6 - 12 mg/d only ) . CONCLUSIONS Results of this study demonstrated that both low- and high-dose cariprazine were more effective than placebo in the treatment of acute manic or mixed episodes associated with bipolar I disorder . Cariprazine was generally well tolerated , although the incidence of akathisia was greater with cariprazine than with placebo . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01058668 OBJECTIVE The authors evaluated the efficacy , safety , and tolerability of cariprazine , an atypical antipsychotic c and i date , in adult patients with acute bipolar I depression . METHOD This was an 8-week multinational , multicenter , r and omized , double-blind , placebo-controlled , parallel-group , fixed-dose study in adult patients with bipolar I disorder experiencing a current major depressive episode . Patients were r and omly assigned ( 1:1:1:1 ) to receive placebo or cariprazine at 0.75 , 1.5 , or 3.0 mg/day . The primary and secondary efficacy parameters were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale ( MADRS ) and the Clinical Global Impressions severity subscale ( CGI-S ) , respectively , analyzed using a mixed-effects model for repeated measures on the modified intent-to-treat population . RESULTS The intent-to-treat population comprised 571 patients ( 141 in the placebo group and 140 , 145 , and 145 in the cariprazine 0.75- , 1.5- , and 3.0-mg/day groups ) . Cariprazine at 1.5 mg/day showed significantly greater improvement on MADRS total score change from baseline to week 6 compared with placebo ; the least squares mean difference was -4.0 ( 95 % CI=-6.3 , -1.6 ; significant after adjustment for multiple comparisons ) . Cariprazine at 3.0 mg/day showed greater MADRS score reduction than placebo ( -2.5 , 95 % CI=-4.9 , -0.1 ; not significant when adjusted for multiple comparisons ) . The 0.75 mg/day dosage was similar to placebo . A similar pattern for significance was observed on the CGI-S ( 1.5 mg/day : least squares mean difference=-0.4 , 95 % CI=-0.6 , -0.1 ; 3.0 mg/day : -0.3 , 95 % CI=-0.5 , -0.0 ) . The most common adverse events ( ≥10 % ) in cariprazine-treated patients were akathisia and insomnia ; weight gain was slightly higher with cariprazine than with placebo . CONCLUSIONS Cariprazine at 1.5 mg/day demonstrated consistent efficacy compared with placebo across outcomes and was generally well tolerated , suggesting efficacy for the treatment of bipolar I depression The purpose of this study was to examine whether prior evidence of an inverse relationship between initial body weight and subsequent antipsychotic-induced weight change represents true effect modification or a statistical artifact , regression to the mean ( RTM ) . We conducted a post-hoc analysis after pooling seven r and omized , placebo- or active-controlled trials of ziprasidone and other antipsychotic agents . ANCOVA was applied to evaluate treatment-by-baseline body mass index ( BMI ) range interaction effect on weight change . Regression analysis was applied to estimate the potential bias due to RTM . Statistical interaction tests between baseline BMI ranges and treatment assignments ( haloperidol , olanzapine , risperidone , or ziprasidone , versus placebo ) were not significant within studies or across studies . Correlation between baseline and follow-up measurements of body weight in placebo-treated subjects was less than perfect ( r=0.87 , 6-month cohort ) , leading to RTM . Consistent with predictions based on RTM , the greatest weight change , on average , was observed in subgroups with baseline weights differing the most from the population mean . Our findings suggest that the previously observed correlation between baseline BMI and weight change subsequent to antipsychotic treatment reflects in part RTM , and not effect modification . This class of drugs appears to cause similar weight gain in both high and low baseline BMI groups OBJECTIVE The authors compared the efficacy and tolerability of low and moderate dosages of extended-release quetiapine in adults with borderline personality disorder . METHOD Ninety-five participants with DSM-IV borderline personality disorder were r and omly assigned to receive 150 mg/day of quetiapine ( the low-dosage group ; N=33 ) , 300 mg/day of quetiapine ( the moderate-dosage group ; N=33 ) , or placebo ( N=29 ) . Total score over time on the clinician-rated Zanarini Rating Scale for Borderline Personality Disorder ( " Zanarini scale " ) was analyzed in a mixed-effects model accounting for informative dropout . RESULTS Participants in the low-dosage quetiapine group had significant improvement on the Zanarini scale compared with those in the placebo group . Time to response ( defined as a reduction of 50 % or more on the Zanarini scale total score ) was significantly shorter for both the low-dosage quetiapine group ( hazard ratio=2.54 , p=0.007 ) and the moderate-dosage quetiapine group ( hazard ratio=2.37 , p=0.011 ) than for the placebo group . Among participants who completed the study , 82 % in the low-dosage quetiapine group were rated as " responders , " compared with 74 % in the moderate-dosage group and 48 % in the placebo group . Treatment-emergent adverse events included sedation , change in appetite , and dry mouth . The overall completion rate for the 8-week double-blind treatment phase was 67 % ( 67 % for the low-dosage quetiapine group , 58 % for the moderate-dosage quetiapine group , and 79 % for the placebo group ) . Participants who experienced sedation were more likely to drop out . CONCLUSIONS Participants treated with 150 mg/day of quetiapine had a significant reduction in the severity of borderline personality disorder symptoms compared with those who received placebo . Adverse events were more likely in participants taking 300 mg/day of quetiapine OBJECTIVE The authors determined the efficacy and safety of asenapine in preventing recurrence of any mood episode in adults with bipolar I disorder . METHOD Adults with an acute manic or mixed episode per DSM-IV-TR criteria were enrolled in this r and omized , placebo-controlled trial consisting of an initial 12- to 16-week open-label period and a 26-week double-blind r and omized withdrawal period . The target asenapine dosage was 10 mg b.i.d . in the open-label period but could be titrated down to 5 mg b.i.d . After completing the open-label period , subjects meeting stabilization/stable-responder criteria were r and omized to asenapine or placebo treatment in the double-blind period . The primary efficacy endpoint was time to recurrence of any mood event during the double-blind period . Kaplan-Meier estimation was performed , and 95 % confidence intervals were determined . Safety was assessed throughout . RESULTS A total of 549 subjects entered the open-label period , of whom 253 enrolled in the double-blind r and omized withdrawal period ( 127 in the placebo group ; 126 in the asenapine group ) . Time to recurrence of any mood episode was statistically significantly longer for asenapine- than placebo-treated subjects . In post hoc analyses , significant differences in favor of asenapine over placebo were seen in time to recurrence of manic and depressive episodes . The most common treatment-emergent adverse events were somnolence ( 10.0 % ) , akathisia ( 7.7 % ) , and sedation ( 7.7 % ) in the open-label period and mania ( 11.9 % of the placebo group compared with 4.0 % of the asenapine group ) and bipolar I disorder ( 6.3 % compared with 1.6 % ) in the double-blind period . CONCLUSIONS Long-term treatment with asenapine was more effective than placebo in preventing recurrence of mood events in adults with bipolar I disorder and was generally well-tolerated OBJECTIVE Cariprazine , a dopamine D3/D2 and 5-HT1A receptor partial agonist , was found to be effective in treating bipolar I depression in a previous phase 2 study . This phase 3 study further assessed the efficacy , safety , and tolerability of cariprazine in bipolar I depression . METHODS In a double-blind placebo-controlled study , adult participants ( 18 - 65 years old ) who met DSM-5 criteria for bipolar I disorder and a current depressive episode were r and omly assigned to receive placebo ( N=158 ) or cariprazine at 1.5 mg/day ( N=157 ) or 3.0 mg/day ( N=165 ) . The primary and secondary efficacy parameters were changes from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale ( MADRS ) score and Clinical Global Impressions severity ( CGI-S ) score , respectively . Least squares mean differences were estimated using a mixed model for repeated measures , and p values were adjusted for multiplicity . RESULTS Both dosages of cariprazine were significantly more effective than placebo in improving depressive symptoms ( reducing MADRS total score ) ; the least squares mean differences were -2.5 ( 95 % CI=-4.6 , -0.4 ) for cariprazine at 1.5 mg/day and -3.0 ( 95 % CI=-5.1 , -0.9 ) for cariprazine at 3.0 mg/day . Both cariprazine dosages were associated with lower CGI-S scores compared with placebo , but the differences did not reach statistical significance after adjustment for multiplicity ( least squares mean difference , -0.2 [ 95 % CI=-0.5 , 0.0 ] for the 1.5 mg/day group and -0.3 [ 95 % CI=-0.5 , 0.0 ] for the 3.0 mg/day group ) . Common treatment-emergent adverse events ( in at least 5 % of participants in either cariprazine treatment group and twice the rate of the placebo group ) were nausea , akathisia , dizziness , and sedation . Mean changes in weight and metabolic parameters were relatively small and comparable across groups . CONCLUSIONS Cariprazine , at both 1.5 mg/day and 3.0 mg/day , was effective , generally well tolerated , and relatively safe in reducing depressive symptoms in adults with bipolar I depression Context Schizophrenia is a chronic disease most frequently necessitating lifelong antipsychotic treatment . Selecting which antipsychotic is to be prescribed in an individual schizophrenia patient represents an important clinical decision that need to take into account efficacy and side effects . Objective Evaluating weight gain related with one year antipsychotic treatment in antipsychotic naive first-episode schizophrenia patients . Design This study is an analysis of weight gain associated with typical or atypical antipsychotics used in European First Episode Schizophrenia Trial ( EUFEST ) study . Subjects and Methods 113 first episode naïve antipsychotic schizophrenia patients included in EUFEST - Romanian cohort , who were r and omized to one of the 5 treatment arms . Weight was obtained at baseline , 3 , 6 , 9 and 12 months for the 5 antipsychotics ( typical-Haloperidol ; atypical-Olanzapine , Amisulpride , Ziprasidone , Quetiapine ) . Results There are no statistically significant differences between groups treated with typical or atypical antipsychotics or between any individual antipsychotics concerning weight gain during the study . Weight gain was the highest in the first 3 months ( 57.49 % ) for all the studied neuroleptics . At the end of the study , the less increase was observed with ziprasidone ( 3.87 kg ) and the highest with olanzapine ( 9.83 kg ) . Conclusion Increase in weight has taken place for each individual neuroleptic , but also as a group ( all neuroleptics ) in the first three months ( 57.49 % ) . Therefore , we should address the issue of weight gain with great care , especially in first period of antipsychotic administration , in order to fast deploy intervention tailored to maintain pre-treatment weight BACKGROUND This Phase III , r and omized , double-blind , placebo-controlled study investigated the efficacy and tolerability of flexibly-dosed cariprazine in patients with acute manic or mixed episodes associated with bipolar I disorder . METHODS Patients were r and omized to 3 weeks of double-blind treatment with cariprazine 3 - 12mg/day ( n=158 ) or placebo ( n=154 ) . The primary efficacy parameter was change from baseline to Week 3 in Young Mania Rating Scale ( YMRS ) total score . The secondary efficacy parameter was change from baseline to Week 3 in Clinical Global Impressions-Severity ( CGI-S ) score . RESULTS Mean change from baseline to Week 3 in YMRS total score was significantly greater for patients receiving cariprazine 3 - 12mg/day versus placebo ( P=0.0004 ) . Significant differences between groups in YMRS total score mean change were observed by Day 4 ( first postbaseline assessment ) and maintained throughout double-blind treatment ( all assessment s , P<0.01 ) . Cariprazine also demonstrated statistically significant superiority over placebo on YMRS response ( ≥50 % improvement : cariprazine , 58.9 % ; placebo , 44.1 % ; P=0.0097 ) and remission ( YMRS total score≤12 : cariprazine , 51.9 % ; placebo , 34.9 % ; P=0.0025 ) and mean change in CGI-S ( P=0.0027 ) score and Positive and Negative Syndrome Scale ( PANSS ) ( P=0.0035 ) total score . The most common cariprazine-related ( ≥10 % and twice placebo ) treatment emergent adverse events ( TEAEs ) were akathisia , extrapyramidal disorder , tremor , dyspepsia , and vomiting . Mean change from baseline in metabolic parameters were generally small and similar between groups . LIMITATIONS Lack of active comparator arm ; short duration of study . CONCLUSION In this study , cariprazine 3 - 12mg/day was effective and generally well tolerated in the treatment of manic and mixed episodes associated with bipolar I disorder Objective : To evaluate the effectiveness of lurasidone as maintenance treatment for schizophrenia . Method : Adults experiencing an acute exacerbation of schizophrenia initially received 12–24 weeks of open-label treatment with lurasidone ( 40–80 mg/d , flexibly dosed ) . Patients who maintained clinical stability for ⩾12 weeks were r and omized in double-blind fashion to placebo or lurasidone ( 40–80 mg/d , flexibly dosed ) for an additional 28-week treatment period . The primary efficacy endpoint was time to relapse ( based on Kaplan – Meier survival analysis ) . Results : A total of 676 patients enrolled in the open-label phase ; 285 met protocol -specified stabilization criteria and were r and omized to lurasidone ( N=144 ) or placebo ( N=141 ) . During the open-label phase , mean Positive and Negative Syndrome Scale total score decreased from 90.1 to 54.4 in patients who met clinical stability criteria and were r and omized . In the double-blind phase , lurasidone significantly delayed time to relapse compared with placebo ( log-rank test , p=0.039 ) , reflecting a 33.7 % reduction in risk of relapse ( Cox hazard ratio ( 95 % confidence interval ) , 0.663 ( 0.447–0.983 ) ; p=0.041 ) . Probability of relapse at the double-blind week 28 endpoint ( based on Kaplan – Meier analysis ) was 42.2 % in the lurasidone group and 51.2 % in the placebo group . Minimal changes in weight , lipid , glucose , and prolactin were observed throughout the study . Conclusions : This multicenter , placebo-controlled , r and omized withdrawal study demonstrated the efficacy of lurasidone for the maintenance treatment of patients with schizophrenia |
1,649 | 25,284,721 | Conclusions Pegfilgrastim reduced the incidence of FN and CIN compared with no prophylaxis .
Most studies showed better efficacy and effectiveness for pegfilgrastim than filgrastim .
Efficacy and safety profiles of lipegfilgrastim and balugrastim were similar to pegfilgrastim | Purpose Pegfilgrastim was introduced over a decade ago .
Other long-acting granulocyte colony-stimulating factors ( G-CSFs ) have recently been developed .
We systematic ally review ed the efficacy , effectiveness and safety of neutropenia prophylaxis with long-acting G-CSFs in cancer patients receiving chemotherapy . | 9083 Background : Teva 's CG-10639 is a long-acting recombinant human albumin-human granulocyte-colony stimulating factor under investigation to prevent chemotherapy-induced neutropenia . Similar to pegfilgrastim ( PEGF ) , CG-10639 stimulates neutrophil and hematopoietic stem cell mobilization from bone marrow to peripheral blood . No clinical ly relevant immunogenicity with CG-10639 has been observed to date . The main objective of this study was to evaluate the safety and effectiveness of CG-10639 versus PEGF in breast cancer patients ( BCA pts ) receiving myelosuppressive therapy . METHODS This phase II/III study was a r and omized , multi-center , active controlled trial in 334 BCA pts receiving doxorubicin/docetaxel ( DOX/DOC ) . The study included a pilot dose escalation phase to identify two CG-10639 doses with similar effects to PEGF ( 6 mg ) , and a main phase powered for efficacy ( non-inferiority ) . During the pilot phase , patients were r and omized to receive CG-10639 30 mg or PEGF one day after DOX/DOC followed by additional cohorts receiving CG-10639 40 mg , 50 mg . The main phase of the study used a r and omized , 3-arm parallel design comparing two doses of CG-10639 and PEGF following DOX 60mg/m2 and DOC 75mg/m2 IV on day 1 for up to four 21-day cycles . The primary endpoint was the duration of severe neutropenia ( DSN ) during cycle 1 in days ( d ) . RESULTS In the pilot phase ( n=78 ) DSN , secondary efficacy parameters and safety were similar across all treatments . CG-10639 40 mg and 50 mg doses were selected for further investigation . In the main phase ( n=256 ) , there were no statistically significant differences in mean DSN between CG-10639 40 mg ( 1.0d ) , CG-10639 50 mg ( 1.3d ) , and PEGF ( 1.2d ) in Cycle 1 . In each cycle , efficacy was comparable based on ANC nadir and recovery , the incidence and duration of Grade 3 or 4 neutropenia , and the incidence of febrile neutropenia . The type and frequency of treatment emergent AEs were similar across treatment groups . CONCLUSIONS These results support the conclusion that CG-10639 is non-inferior to PEGF based on mean DSN in BCA pts receiving myelosuppressive therapy . The overall safety profile was similar for CG-10639 and PEGF . A phase III , confirmatory study comparing CG-10639 40 mg to PEGF 6 mg is underway BACKGROUND Colony-stimulating factors ( CSFs ) significantly decrease the risk of febrile neutropenia ( FN ) , a common complication of myelosuppressive chemotherapy . Pegfilgrastim ( 6 mg ) , introduced in 2002 , has a sustained duration of action , with a single dose comparable in efficacy to daily injections of filgrastim ( 5 g per kg per day ) for 10 to 11 days ; both agents should be initiated 24 hours after completing chemotherapy . OBJECTIVES To ( 1 ) describe the use of pegfilgrastim and filgrastim in oncology practice s throughout the United States and ( 2 ) compare their effectiveness in actual practice as measured by the outcome of febrile neutropenia in patients who received chemotherapy regimens administered every 3 to 4 weeks for breast , lung , ovarian , colon cancer , or lymphoma and who received a CSF prior to developing FN . METHODS Data were retrospectively obtained from the medical records of a cohort of adult patients aged 18 years or older treated in 99 community oncology practice s in the United States in 2001 and 2003 . Eligible patients were treated with chemotherapy every 3 to 4 weeks for breast , lung , ovarian , colon cancer , or lymphoma and were users of filgrastim in 2001 ( prior to the U.S. Food and Drug Administration approval of pegfilgrastim in January 2002 ) or users of either filgrastim or pegfilgrastim or both CSF agents in 2003 . RESULTS Pegfilgrastim was initiated , on average , 2.4 days ( SD + /-3.2 ) after chemotherapy in the first cycle of use and 1.9 ( + /-3.0 ) days in subsequent cycles of use . In contrast , filgrastim was started on average 7.7 ( + /-6.5 ) days and 4.9 ( 4.6 ) days after chemotherapy in the first and subsequent cycles of use in 2001 , increasing to 9.6 ( + /-6.2 ) and 6.4 ( + /-6.4 ) days in 2003 . In the first cycle of CSF use , filgrastim was administered for an average of 5.2 ( + /-3.5 ) days to 583 patients in 2001 and 3.7 ( + /-2.8 ) days to 868 patients in 2003 ( P < 0.001 ) . Among patients who received more than 1 cycle of filgrastim ( n = 457 in 2001 and n = 489 in 2003 ; 78.4 % and 56.3 % of filgrastim users , respectively ) , the mean days of filgrastim administered in subsequent cycles was 6.0 ( + /-3.5 ) in 2001 and 4.6 ( + /-3.2 ) in 2003 . Pegfilgrastim was administered as a single dose per chemotherapy course to 1,412 patients in 2003 . Patients who received pegfilgrastim were more likely to have at least 1 myelosuppressive drug ( 74.8 % ) in the regimen compared with patients who received filgrastim in 2003 ( 70.0 % , P = 0.013 ) , but a greater proportion of filgrastim patients in 2003 ( 19.4 % ) had advanced-stage disease compared with pegfilgrastim patients ( 14.8 % , P = 0.005 ) . More patients who received filgrastim in 2003 ( 36.2 % ) had a cancer other than breast cancer or non-Hodgkin 's lymphoma compared with those who received pegfilgrastim ( 29.5 % , P = 0.001 ) . A total of 94 of 1,451 patients ( 6.5 % ) who received filgrastim experienced FN compared with 67 of 1,412 patients ( 4.7 % ) for pegfilgrastim . The odds ratio of developing FN among patients who received filgrastim versus pegfilgrastim was 1.41 ( 95 % confidence interval , 1.02 - 1.96 ; P = 0.040 ) after adjusting for patient and chemotherapy regimen characteristics . CONCLUSION In this retrospective study of patients treated in 99 community oncology practice s , patients who received filgrastim often initiated treatment later than recommended and received fewer days per cycle than demonstrated to be effective in r and omized controlled trials . Pegfilgrastim was generally initiated earlier within the course of chemotherapy compared with filgrastim , and because of its sustained duration of action , only a single injection was required . In these patients treated with a heterogeneous group of chemotherapy regimens with a broad range of risk of FN , overall , an absolute 1.8 % increase in the incidence of developing FN was observed in patients who received filgrastim compared with patients who received pegfilgrastim , ( absolute rates of 6.5 % and 4.7 % , respectively ) BACKGROUND TAC ( docetaxel/doxorubicin/cyclophosphamide ) is associated with high incidences of grade 4 neutropenia and febrile neutropenia ( FN ) . This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC . PATIENTS AND METHODS Patients with stage T2-T4 primary breast cancer were scheduled to receive 6 - 8 cycles of TAC . Primary prophylaxis was : ciprofloxacin 500 mg orally twice daily on days 5 - 14 ( n = 253 patients ; 1478 cycles ) , daily granulocyte colony-stimulating factor ( G-CSF ) ( filgrastim 5 microg/kg/day or lenograstim 150 microg/m(2)/day ) on days 5 - 10 ( n = 377 ; 2400 cycles ) , pegfilgrastim 6 mg on day 2 ( n = 305 ; 1930 cycles ) , or pegfilgrastim plus ciprofloxacin ( n = 321 ; 1890 cycles ) . RESULTS Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN ( 5 % and 7 % versus 18 % and 22 % of patients ; all P < 0.001 ) , grade 4 neutropenia , and leukopenia . Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN ( P < 0.01 versus pegfilgrastim alone ) and fatal neutropenic events . CONCLUSION Ciprofloxacin alone , or daily G-CSF from day 5 - 10 ( as in common practice ) , provided suboptimal protection against FN and related toxic effects in patients receiving TAC . Pegfilgrastim was significantly more effective in this setting , especially if given with ciprofloxacin PURPOSE We evaluated the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia associated with docetaxel in breast cancer patients . PATIENTS AND METHODS Patients were r and omly assigned to either placebo or pegfilgrastim 6 mg subcutaneously on day 2 of each 21-day chemotherapy cycle of 100 mg/m(2 ) docetaxel . The primary end point was the percentage of patients developing febrile neutropenia ( defined as body temperature > /= 38.2 degrees C and neutrophil count < 0.5 x 10(9)/L on the same day of the fever or the day after ) . Secondary end points were incidence of hospitalizations associated with a diagnosis of febrile neutropenia , intravenous ( IV ) anti-infectives required for febrile neutropenia , and the ability to maintain planned chemotherapy dose on time . Patients with febrile neutropenia were converted to open-label pegfilgrastim in subsequent cycles . RESULTS Nine hundred twenty-eight patients received placebo ( n = 465 ) or pegfilgrastim ( n = 463 ) . Patients receiving pegfilgrastim , compared with patients receiving placebo , had a lower incidence of febrile neutropenia ( 1 % v 17 % , respectively ; P < .001 ) , febrile neutropenia-related hospitalization ( 1 % v 14 % , respectively ; P < .001 ) , and use of IV anti-infectives ( 2 % v 10 % , respectively ; P < .001 ) . The percentage of patients receiving the planned dose on time was similar between patients receiving pegfilgrastim and patients who initially received placebo ( 80 % and 78 % , respectively ) , as would be expected of the study design . Pegfilgrastim was generally well tolerated and safe , and the adverse events reported were typical of this patient population . CONCLUSION First and subsequent cycle use of pegfilgrastim with a moderately myelosuppressive chemotherapy regimen markedly reduced febrile neutropenia , febrile neutropenia-related hospitalizations , and IV anti-infective use Aim : Febrile neutropenia ( FN ) is a highly prevalent complication of chemotherapy , particularly in patients with non‐Hodgkin 's lymphoma . This study aim ed to compare the efficacy of filgrastim and pegfilgrastim in Asian lymphoma patients by evaluating the incidence of FN and associated complications Aim of the study PROFIL was a prospect i ve observational study conducted to investigate physicians ’ evaluation of febrile neutropenia ( FN ) risk and reasons for giving pegfilgrastim primary prophylaxis ( PP ) in routine clinical practice in Pol and . Material and methods Adult cancer patients treated with chemotherapy ( CT ) , assessed by investigators as having high overall FN risk , and who received pegfilgrastim in cycle 1 were enrolled between 03/2009 and 09/2010 . Investigators assessed FN risk of the CT regimen , individual risk factors , and overall FN risk , and were asked to provide the most important reasons for providing pegfilgrastim PP . Investigator-assessed CT FN risk was compared with guideline classification . Results Data were analysed from 1006 breast , ovarian , and lung cancer , and non-Hodgkin ( NHL ) and Hodgkin lymphoma ( HL ) patients . The most important reasons for using pegfilgrastim PP were high CT FN risk and advanced disease ; these were consistent across tumour types and treatment intent . The investigators generally assessed high CT FN risk in agreement with guideline classification . Febrile neutropenia occurred in 4 % of patients , most commonly in HL , NHL , and patients with advanced disease . Conclusions High CT FN risk and advanced stage of disease were found to be the most important reasons for providing pegfilgrastim PP by physicians in Pol and Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more PURPOSE This multicenter , r and omized , double-blind , active-control study was design ed to determine whether a single subcutaneous injection of pegfilgrastim ( SD/01 , sustained- duration filgrastim ; 100 microg/kg ) is as safe and effective as daily filgrastim ( 5 microg/kg/d ) for reducing neutropenia in patients who received four cycles of myelosuppressive chemotherapy . PATIENTS AND METHODS Sixty-two centers enrolled 310 patients who received chemotherapy with docetaxel 75 mg/m(2 ) and doxorubicin 60 mg/m(2 ) on day 1 of each cycle for a maximum of four cycles . Patients were r and omized to receive on day 2 either a single subcutaneous injection of pegfilgrastim 100 microg/kg per chemotherapy cycle ( 154 patients ) or daily subcutaneous injections of filgrastim 5 microg/kg/d ( 156 patients ) . Absolute neutrophil count ( ANC ) , duration of grade 4 neutropenia , and safety parameters were monitored . RESULTS One dose of pegfilgrastim per chemotherapy cycle was comparable to daily subcutaneous injections of filgrastim with regard to all efficacy end points , including the duration of severe neutropenia and the depth of ANC nadir in all cycles . Febrile neutropenia across all cycles occurred less often in patients who received pegfilgrastim . The difference in the mean duration of severe neutropenia between the pegfilgrastim and filgrastim treatment groups was less than 1 day . Pegfilgrastim was safe and well tolerated , and it was similar to filgrastim . Adverse event profiles in the pegfilgrastim and filgrastim groups were similar . CONCLUSION A single injection of pegfilgrastim 100 microg/kg per cycle was as safe and effective as daily injections of filgrastim 5 microg/kg/d in reducing neutropenia and its complications in patients who received four cycles of doxorubicin 60 mg/m(2 ) and docetaxel 75 mg/m(2 ) Introduction : We investigated dose-dense docetaxel and cisplatin in patients with measurable non-small cell lung cancer in a r and omized phase II study without [ A ] or with [ B ] a putative chemoprotective agent , BNP7787 . Patients and Methods : Chemotherapy-naive patients with stage IIIB ( effusion ) or IV , performance status 0 to 1 , and adequate organ function were eligible . Treatment with docetaxel 75 mg/m2 followed by cisplatin 75 mg/m2 over 1 hour day 1 with darbepoetin 200 & mgr;g day 1 and pegfilgrastim 6 mg day 2 without/with BNP7787 before cisplatin was repeated every other week for up to 6 cycles . The primary end point was to differentiate between grade ≥2 neurotoxicity rates of 30 % on [ A ] and 10 % on [ B ] . Feasibility was prospect ively defined as febrile neutropenia in < 10 % of patients and ≤1 treatment delay per cycles 1 to 3 and 4 to 6 in < 20 % of patients . Results : Of 160 patients enrolled , 5 never started therapy and 4 were ineligible . Neurotoxicity grade ≥2 occurred in 32 % on [ A ] and 29 % on [ B ] . The incidence of febrile neutropenia was 4 % on [ A ] and 3 % on [ B ] . Treatment delays occurred in 13 % and 20 % of patients on [ A ] and [ B ] , respectively . Completion rates for 3/6 cycles were 84%/51 % on [ A ] and 84%/53 % on [ B ] . Objective response rates were 55 % on [ A ] and 51 % on [ B ] . Median progression-free/overall survival times were 5.5/10.7 on [ A ] and 6.5/14.1 month on [ B ] . Conclusions : This dose-dense treatment regimen is active , feasible , and tolerable . Its further investigation in the curative setting in non-small cell lung cancer should be considered . BNP7787 did not result in significant protection from neurotoxicity Abstract Background Lipegfilgrastim is a novel glyco-pegylated granulocyte-colony stimulating factor in development for neutropenia prophylaxis in cancer patients receiving chemotherapy . This phase III , double-blind , r and omized , active-controlled , noninferiority trial compared the efficacy and safety of lipegfilgrastim versus pegfilgrastim in chemotherapy-naïve breast cancer patients receiving doxorubicin/docetaxel chemotherapy . Methods Patients with high-risk stage II , III , or IV breast cancer and an absolute neutrophil count ≥1.5 × 109 cells/L were r and omized to a single 6-mg subcutaneous injection of lipegfilgrastim ( n = 101 ) or pegfilgrastim ( n = 101 ) on day 2 of each 21-day chemotherapy cycle ( 4 cycles maximum ) . The primary efficacy endpoint was the duration of severe neutropenia during cycle 1 . Results Cycle 1 : The mean duration of severe neutropenia for the lipegfilgrastim and pegfilgrastim groups was 0.7 and 0.8 days , respectively ( λ = −0.218 [ 95 % confidence interval : –0.498 % , 0.062 % ] , p = 0.126 ) , and no severe neutropenia was observed in 56 % and 49 % of patients in the lipegfilgrastim and pegfilgrastim groups , respectively . All cycles : In the efficacy population , febrile neutropenia occurred in three pegfilgrastim-treated patients ( all in cycle 1 ) and zero lipegfilgrastim-treated patients . Drug-related adverse events in the safety population were reported in 28 % and 26 % of patients in the lipegfilgrastim and pegfilgrastim groups , respectively . Conclusion This study demonstrates that lipegfilgrastim 6 mg is as effective as pegfilgrastim in reducing neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy . Trial Registration Eudra EEACTA200901599910 The study protocol , two global amendments ( Nos. 1 and 2 ) , informed consent documents , and other appropriate study -related documents were review ed and approved by the Ministry of Health of Ukraine Central Ethics Committee and local independent ethics committees ( IECs ) The impact of first- and subsequent-cycle growth factor use in the community setting has not been studied extensively . We conducted this large , prospect i ve , noncomparative study to assess neutropenia and related complications in patients receiving myelotoxic chemotherapy with pegfilgrastim support in community practice s. Patients > or = 18 years old with cancers other than leukemia or myelodysplastic syndrome , including those with major comorbidities , were eligible . Pegfilgrastim ( 6 mg ) was to be administered approximately 24 hours after chemotherapy in all cycles ( minimum , four cycles ) . A total of 2,112 patients was included in the analyses . The most common tumor types were breast cancer ( 46 % ) , non-Hodgkin 's lymphoma ( 15 % ) , and non-small cell lung cancer ( 13 % ) . Chemotherapies administered most often were a platinum plus a taxane ( 18 % ) , and anthracycline plus an alkylating agent ( 18 % ) , and a taxane plus an anthracycline plus an alkylating agent ( 16 % ) . The percentage of patients with neutropenia-related hospitalization was 2.9 % in cycle 1 and 5.6 % across all cycles . Chemotherapy dose reductions and delays were attributed to neutropenia in 1.8 % and 0.9 % of patients , respectively , in cycle 2 and 2.9 % and 2.1 % of patients , respectively , across all cycles . Febrile neutropenia ( absolute neutrophil count < 1.0 x 10(9)/l with temperature > or = 38.2 degrees C ) occurred in 3.6 % of patients in cycle 1 and in 6.3 % of patients across all cycles . The most frequently reported serious adverse events were febrile neutropenia ( 3.4 % ) , neutropenia ( 2.6 % ) , and dehydration ( 2.6 % ) . Bone pain ( 0.1 % ) was the only related serious adverse event reported in more than one patient . Data from this community-based study suggest that patients undergoing chemotherapy benefit from pegfilgrastim support beginning in the first cycle of chemotherapy BACKGROUND In a meta- analysis of data from r and omized trials , the risk of febrile neutropenia during myelosuppressive chemotherapy was reported to be lower with pegfilgrastim prophylaxis than filgrastim prophylaxis . However , there is limited information on the comparative effectiveness of these agents in clinical practice . OBJECTIVE This study was undertaken to compare the risks of hospitalization for neutropenic complications of chemotherapy in US clinical practice in patients with primary solid tumors receiving pegfilgrastim or filgrastim prophylaxis . METHODS This was a retrospective cohort study employing a US health insurance data base . The source population included all patients who received chemotherapy for a primary solid tumor between January 2003 and December 2005 and who received filgrastim or pegfilgrastim during their first course of chemotherapy . All unique chemotherapy cycles were identified for each patient , and cycles in which pegfilgrastim or filgrastim was administered by cycle day 5 ( considered to represent prophylaxis ) were selected and pooled for analysis . The risks of hospitalization for neutro-penic complications ( using both narrow and broad criteria ) and for any reason were then compared between cycles in which filgrastim or pegfilgrastim prophylaxis was administered . Generalized estimating equations were used to control for potential confounding variables . RESULTS Filgrastim prophylaxis was used in 1193 unique chemotherapy cycles ( mean [ SD ] number of days per cycle , 4.5 [ 3.3 ] ) ; for pegfilgrastim prophylaxis , the number of unique chemotherapy cycles was 14,570 . First-cycle use represented 16 % of all cycles analyzed . The mean ages of patients receiving filgrastim and pegfilgrastim prophylaxis were 61 and 60 years , respectively . Breast cancer was the most common tumor type ( 52 % and 51 % ) , followed by non-Hodgkin 's lymphoma ( 21 % and 18 % ) and lung cancer ( 11 % and 15 % ) . Hospitalization for neutropenic complications ( narrow criterion ) occurred during 2.1 % of filgrastim cycles and 1.2 % of pegfilgrastim cycles ; hospitalization for neutropenic complications ( broad criterion ) occurred in a respective 4.8 % and 3.1 % of cycles ; and hospitalization for all causes occurred in 8.7 % and 6.3 % of cycles ( all , P < 0.01 ) . The risks of hospitalization were consistently lower for chemotherapy cycles that involved pegfilgrastim prophylaxis compared with filgrastim prophylaxis ( odds ratios = 0.64 - 0.73 ; P < 0.05 ) . CONCLUSION The risk of hospitalization for neutro-penic complications during cancer chemotherapy in clinical practice was approximately one third higher among patients who received filgrastim prophylaxis than among those who received pegfilgrastim prophylaxis BACKGROUND Adding irinotecan and /or oxaliplatin to every-2-week 5-fluorouracil (5-FU)/leucovorin ( LV ) prolongs survival in patients with colorectal cancer ( CRC ) but increases neutropenia frequency . Pegfilgrastim is indicated to decrease infection as manifested by febrile neutropenia ( FN ) in patients receiving chemotherapy at > 14-day intervals . This r and omized , placebo-controlled phase II study examined pegfilgrastim efficacy and safety in patients with CRC receiving every-2-week chemotherapy . PATIENTS AND METHODS Patients with CRC were r and omized 1:1 to pegfilgrastim 6 mg or placebo administered per-cycle on day 4 . R and omization was stratified by chemotherapy regimen ( patients received every-2-week FOLFOX4 [ 5-FU/LV/oxaliplatin ] , FOLFIRI [ 5-FU/LV/irinotecan ] , or FOIL [ 5-FU/LV/oxaliplatin/irinotecan ] at physician discretion ) . The primary endpoint was incidence of grade 3/4 neutropenia . Secondary endpoints included incidence of grade 3/4 FN and adverse events . After 4 cycles of study treatment , progression-free survival ( PFS ) and overall survival ( OS ) were followed for < or= 2 years in long-term follow-up . RESULTS Of 241 eligible patients analyzed , 118 were in the placebo and 123 in the pegfilgrastim group . In the treatment period , the odds ratio for grade 3/4 neutropenia for pegfilgrastim versus placebo was 0.19 ( 95 % CI , 0.10 - 0.37 ; P < .001 ) ; grade 3/4 FN incidence was also significantly lower in pegfilgrastim-treated patients ( 2 % ) compared with placebo-treated patients ( 8 % ; P = .04 ) . Pegfilgrastim was well tolerated , with leukocyte counts remaining stable during cycles 2 - 4 . In long-term follow-up , both treatment groups had similar PFS and OS . CONCLUSION Pegfilgrastim was well tolerated in patients with CRC receiving every-2-week chemotherapy and significantly reduced neutropenia and FN compared with placebo , though FN was uncommon in both treatment groups . Results suggest that pegfilgrastim administration is feasible in CRC patients receiving every-2-week chemotherapy Abstract Objective : To determine if granulocyte-colony-stimulating factor ( G-CSF ) primary prophylaxis is associated with a lower risk of febrile neutropenia ( FN ) than non- primary prophylaxis . Methods : This was a retrospective , cohort study of medical records from a r and om sample of patients with solid tumours and lymphomas treated in 99 community oncology practice s in 2003 ( n=5319 ) . Consecutively- sample d patients treated with chemotherapy and either filgrastim ( Neupogen*,† ) , pegfilgrastim ( Neulasta*,† ) or no G-CSF were included ( n=3123 ) . Multivariate logistic regression estimated the odds of FN in patients receiving G-CSF primary prophylaxis ( within 3 days of first chemotherapy cycle ) compared with non- primary prophylaxis ( delayed or no G-CSF ) . Results : Patients receiving primary prophylaxis were less likely to develop FN than patients receiving non- primary prophylaxis ( OR=0.49 , 95 % CI 0.34–0.71 , p<0.001 ) . Chemotherapy characteristics were associated with development of FN including , receipt of at least three chemotherapy drugs versus one ( OR=2.13 , 95 % CI 1.17–3.89 , p=0.014 ) and regimens with at least one myelosuppressive drug ( OR=2.37 , 95 % CI 1.19–4.73 , p=0.014 ) . Conclusion : Patients receiving G-CSF primary prophylaxis had significantly lower odds of developing FN than those receiving non- primary prophylaxis . Incidence of FN may be underestimated , as care not recorded in the medical oncologist 's chart was not captured Every-2-week ( dose-dense ) adjuvant doxorubicin ( A ) plus cyclophosphamide ( C ) followed by cremophor-formulated paclitaxel ( cf-P ) was efficacious in metastatic breast cancer ( BC ) . Albumin-bound paclitaxel ( ab-P ) was safe and more effective than cf-P , and the addition of bevacizumab to cf-P improved efficacy . This study compared the safety of dose-dense ab-P vs cf-P plus bevacizumab following dose-dense adjuvant AC for early-stage BC . Patients and Methods : Women with operable , histologically confirmed BC were r and omized to 4 cycles of dose-dense A 60 mg/m2 plus C 600 mg/m2 IV with SC pegfilgrastim , followed by 4 cycles of either dose-dense IV ab-P 260 mg/m2 or cf-P 175 mg/m2 . Bevacizumab was given during and following chemotherapy . 97 and 96 % of patients completed 4 cycles of AC therapy , while 84 and 85 % of patients completed 4 cycles of taxane therapy in the ab-P and cf-P arms , respectively ( N = 197 ) . Baseline patient characteristics were similar . The most common grade ≥3 taxane-related adverse events ( AEs ) were fatigue and neutropenia . Dose reductions were similar between the treatment arms . During AC therapy , the majority of dose reductions were due to febrile neutropenia ; during taxane therapy , the majority of cases were due to neuropathy . No taxane-related dose interruption occurred in the ab-P arm , while 3 occurred in the cf-P arm due to hypersensitivity reactions . The mean cumulative paclitaxel dose was 950.5 and 660.8 mg/m2 in the ab-P and cf-P arms , respectively . A 44 % higher paclitaxel dose was delivered in the ab-P compared with the cf-P arm ( P < 0.0001 ) , while achieving a similar safety profile . ab-P plus bevacizumab following AC therapy without prophylactic premedications was tolerable in early-stage BC patients Background Preliminary data suggest that pegfilgrastim given on day 4 ( P4 ) might be superior to pegfilgrastim on day 2 ( P2 ) in reducing grade 4 leucopenia . Methods Patients with node-positive primary breast cancer receiving epirubicin – paclitaxel – cyclophosphamide chemotherapy were r and omized to receive P2 versus P4 . Primary endpoint was leucopenia grade 4 , assuming a risk reduction of 50 % with P4 from 50 % in P2 to 25 % with P4 . Results Three-hundred fifty-one patients were r and omized to P2 ( n = 174 ) versus P4 ( n = 177 ) . The rate of leucopenia ( grade 4 ) was 47.1 % with P2 and 42.0 % with P4 ( p = 0.387 ) , neutropenia ( grade 3 + 4 ) was 47.9 % versus 40.8 % ( p = 0.337 ) , FN was 4.7 % versus 8.0 % ( p = 0.271 ) , and infections was 29.9 % versus 25.4 % ( p = 0.404 ) , respectively . Conclusion This study failed to demonstrate that pegfilgrastim on day 4 was more efficacious than on day 2 with respect to grade 4 leucopenia ( the primary endpoint ) , febrile neutropenia , or infections 9080 Background : XM22 is a glyco-PEGylated r-metHuG-CSF that is being developed for the reduction of duration of severe neutropenia and incidence of febrile neutropenia in cancer patients undergoing chemotherapy . R and omized , single-blind studies in healthy volunteers have evaluated the pharmacokinetics , pharmacodynamics , and safety of long-acting , subcutaneously ( sc ) administered XM22 in comparison to Pegfilgrastim ( PEGF ) . The primary objective of the XM22 - 02-INT study was to identify the optimal fixed dose of XM22 compared to PEGF in primary breast cancer patients receiving chemotherapy ( CTX ) . METHODS This study was a multinational , multicenter , r and omized , double-blind , controlled study evaluating the efficacy and safety of fixed doses of XM22 compared to 6 mg of PEGF in breast cancer patients receiving 4 cycles of doxorubicin 60 mg/m2 and docetaxel 75 mg/m2 . XM22 ( 3 mg , 4.5 mg , or 6 mg ) or PEGF ( 6 mg ) was administered sc approximately 24 hours after CTX on each of the 4 cycles . The primary endpoint was the duration of severe neutropenia ( DSN ) in cycle 1 . Secondary endpoints included DSN in cycles 2 - 4 , duration and incidence of severe neutropenia , febrile neutropenia , ANC values , ANC nadir , time to ANC nadir and recovery . Pharmacokinetic parameters were also analyzed . RESULTS A total of 229 patients were screened and 208 r and omized to XM22 3 mg ( n=53 ) , XM22 4.5 mg ( n=51 ) , XM22 6 mg ( n=50 ) , and PEGF ( n=54 ) . Six patients did not complete the study . Demographic and baseline characteristics were comparable across the treatment groups . DSN in cycle 1 was 1.1 , 0.8 , 0.8 , and 0.9 days in the XM22 3 mg , 4.5 mg , 6 mg and PEGF groups , respectively . Using multivariate Poisson regression for the primary endpoint , greater efficacy was seen with higher XM22 doses . Secondary endpoints also suggested greater efficacy with increased XM22 dose . Treatment-emergent adverse events were similar between the treatment groups . CONCLUSIONS DSN in cycle 1 was similar for all treatment groups ( mean = 0.9 days ) , however , there was a clear trend to shorter DSN with higher XM22 doses . The study supported the use of XM22 6 mg in the phase III comparative study versus PEGF Dose density during early induction has been demonstrated to be one of the prime determinants for treatment efficacy in acute myeloid leukemia ( AML ) . The German AML Cooperative Group has therefore piloted a dose-dense induction regimen sequential high-dose AraC and mitoxantrone followed by pegfilgrastim ( S-HAM ) in which 2 induction cycles are applied over 11 to 12 days instead of 25 to 29 days as used in conventional double induction , thereby increasing dose density 2-fold . Of 172 de novo AML patients ( excluding acute promyelocytic leukemia ) , 61 % reached a complete remission , 22 % a complete remission with incomplete peripheral recovery , 7 % had persistent leukemia , 10 % died ( early death ) result ing in an overall response rate of 83 % . Kaplan-Meier estimated survival at 2 years was 61 % for the whole group ( patients with unfavorable karyotypes , 38 % ; patients with favorable karyotypes , 69 % ; patients with intermediate karyotypes , 75 % ) after S-HAM treatment . Importantly , the compression of the 2 induction cycles into the first 11 to 12 days of treatment was beneficial for normal hematopoiesis as demonstrated by a significantly shortened duration of critical neutropenia of 31 days compared with 46 days after conventionally timed double induction BACKGROUND Most alterations to chemotherapy dose and schedule are because of neutropenic events , which mainly occur in the first chemotherapy cycle . This prospect i ve , community-based study evaluated the effectiveness of pegfilgrastim in patients with lymphoma who were also receiving chemotherapy . PATIENTS AND METHODS Patients aged > or = 18 years with cancer other than leukemia or myelodysplastic syndromes were eligible , including patients with major comorbidities who were generally not eligible for most clinical trials . Key exclusions were weekly chemotherapy and concurrent radiation therapy . Patients received pegfilgrastim 6 mg approximately 24 hours after chemotherapy in each cycle ( up to 8 cycles ) . Endpoints included neutropenic complications and serious adverse events . RESULTS This open-label single-arm study enrolled 2249 patients at 319 sites . Of these 2249 patients , 325 patients with non-Hodgkin lymphoma ( NHL ) and 46 patients with Hodgkin disease were included in the primary analysis set . The median age was 65 years for patients with NHL and 41 years for patients with Hodgkin disease , and 31 % and 26 % had major comorbidities , respectively . Few patients experienced neutropenic complications , including grade 4 febrile neutropenia ( patients with Hodgkin disease : 0 [ 95 % confidence interval ( CI ) , 0 - 8 % ] ; patients with NHL : 13 % [ 95 % CI , 10%-17 % ] ) ; febrile neutropenia-related hospitalization ( patients with Hodgkin disease : 0 [ 95 % CI , 0 - 8 % ] ; patients with NHL : 10 % [ 95 % CI , 7%-14 % ] ) , neutropenia-related dose reduction ( patients with Hodgkin disease : 0 [ 95 % CI , 0 - 8 % ] ; patients with NHL : 5 % [ 95 % CI , 3%-8 % ] ) , and neutropenia-related dose delay ( patients with Hodgkin disease : 0 [ 95 % CI , 0 - 8 % ] ; patients with NHL : 5 % [ 95 % CI , 3%-8 % ] ) . Serious adverse events were consistent with those observed in patients receiving myelosuppressive chemotherapy . CONCLUSION Patients with lymphoma receiving myelosuppressive chemotherapy supported by pegfilgrastim experienced few neutropenic complications or neutropenia-related alterations in chemotherapy dose and schedule BACKGROUND There is a misconception that elderly cancer patients can not tolerate st and ard doses of chemotherapy because of the frequency and severity of myelosuppressive complications . The reactive use of colony-stimulating factors ( i.e. , in response to severe neutropenia ) commonly observed in this setting contributes to the frequency and severity of these complications . This study evaluated the incidence of febrile neutropenia and related events in elderly cancer patients receiving pegfilgrastim beginning with cycle 1 ( proactive ) in comparison with pegfilgrastim initiated after cycle 1 at the physician 's discretion ( reactive ) . METHODS Patients ( > or = 65 years of age ) with either solid tumors or non-Hodgkin 's lymphoma ( NHL ) were r and omly assigned to receive pegfilgrastim either proactively or reactively . The primary endpoint was the proportion of patients experiencing febrile neutropenia . RESULTS There were 852 patients enrolled ( median age , 72 years ) . Proactive pegfilgrastim use result ed in a significantly lower incidence of febrile neutropenia for both solid tumor and NHL patients compared with reactive use . Proactive pegfilgrastim use also led to fewer hospitalizations result ing from neutropenia and febrile neutropenia by approximately 50 % . Antibiotic use was lower for solid tumor patients receiving proactive pegfilgrastim and equivalent in the two NHL groups . CONCLUSIONS This is the largest , r and omized , prospect i ve trial evaluating growth factor support in typical elderly cancer patients . Proactive pegfilgrastim use effectively produced a lower incidence of febrile neutropenia and related events in elderly patients with either solid tumors or NHL receiving an array of mild to moderately neutropenic chemotherapy regimens . Pegfilgrastim should be used proactively in elderly cancer patients to support the optimal delivery of st and ard chemotherapy Purpose This prospect i ve , nonr and omized study evaluates 4 schedules of granulocyte colony-stimulating factor ( G-CSF ) for patients with breast cancer receiving adjuvant dose-dense chemotherapy regarding febrile neutropenia , treatment delays , and costs . Patients and Methods Two hundred and thirty-one patients were enrolled to receive adjuvant dose-dense chemotherapy with 4 G-CSF schedules : filgrastim ( 300 mcg ) days 3 to 10 [ n = 84 ( 36.4 % ) group A ] ; days 3 to 7 [ n = 26 ( 11.3 % ) group B ] ; days 5 , 7 , 9 , and 11 [ n = 64 ( 27.7 % ) group C ] , or pegfilgrastim ( 6 mg ) on day 2 [ n=57 ( 24.6 % ) group D ] . Results Thirteen patients were hospitalized due to 14 episodes of febrile neutropenia ; 3 in group A , 3 in group B , 1 in group C , and 6 in group D. No statistically significant difference was observed among the 4 groups . Fewer febrile neutropenic events were observed in group C than in group D ( P=0.041 ) . No statistically significant differences were observed in treatment delays or other hematological toxicities . Average overall G-CSF cost per patient in groups A and D was $ 8500 versus $ 4400 in groups B and C. Conclusions We found a trend in favor of the shorter G-CSF schedule . A larger , prospect i ve r and omized trial should be carried out to evaluate shorter versus st and ard filgrastim and pegfilgrastim schedules with regard to clinical outcomes , hematological and nonhematological toxicities , and impact in costs BACKGROUND Neoadjuvant anthracycline/taxane combinations , with or without gemcitabine , produce pathologic complete responses ( pCRs ) in 15%-25 % of patients . In this multicenter phase II study , we attempted to increase efficacy and decrease toxicity of a 3-drug gemcitabine-containing neoadjuvant regimen by administering dose-dense therapy with pegfilgrastim , and including albumin-bound paclitaxel as the taxane . PATIENTS AND METHODS A total of 123 patients with locally advanced breast cancer were enrolled . Patients were treated with 6 doses of neoadjuvant gemcitabine 2000 mg/m2 , epirubicin 50 mg/m2 , and albumin-bound paclitaxel 175 mg/m2 intravenously administered at 14-day intervals . Following neoadjuvant chemotherapy , patients underwent either mastectomy or breast conservation surgery ; pathologic response to treatment was assessed . Postoperatively , patients received 4 doses of gemcitabine 2000 mg/m2 with albumin-bound paclitaxel 220 mg/m2 at 14-day intervals . Pegfilgrastim 6 mg was administered subcutaneously on day 2 following each dose of chemotherapy . RESULTS A total of 116 patients ( 95 % ) completed neoadjuvant chemotherapy and had subsequent surgical resection . Twenty-three patients ( 20 % ) had a pCR . The estimated 3-year progression-free survival ( PFS ) and overall survival rates were 48 % and 86 % , respectively . Neoadjuvant treatment was well tolerated ; only 11 % of the patients had grade 3/4 neutropenia , with 1 episode of neutropenic fever . Other grade 3/4 toxicities occurred in < 10 % of the patients . CONCLUSION Neoadjuvant biweekly chemotherapy with gemcitabine/epirubicin/albumin-bound paclitaxel with pegfilgrastim is feasible and well tolerated . The pCR rate of 20 % and the 3-year PFS rate of 48 % are similar to results achieved with other commonly used neoadjuvant regimens PURPOSE Dose-dense , every-2-week adjuvant chemotherapy using doxorubicin/cyclophosphamide ( AC ; 60/600 mg/m2 every 2 weeks x four cycles ) followed by paclitaxel ( 175 mg/m2 every 2 weeks x four cycles ) , requiring filgrastim on days 3 through 10 of each cycle has been shown to improve survival compared with every-3-week treatment schedules but is associated with greater risk of RBC transfusion ( 13 % ) . The role of long-acting hematopoietic growth factors in facilitating every-2-week chemotherapy and minimizing hematologic toxicity has not been established . PATIENTS AND METHODS Women with stage I to III breast cancer received dose-dense AC -- > paclitaxel as neoadjuvant or adjuvant chemotherapy . Patients received pegfilgrastim 6 mg subcutaneous ( SQ ) on day 2 of each cycle . Darbepoetin alfa was initiated at 200 microg SQ every 2 weeks for hemoglobin < or = 12 g/dL , and administered thereafter , according to a preplanned algorithm . The primary end points were to evaluate the percentage of patients with febrile neutropenia and the percentage of patients requiring RBC transfusion . RESULTS Among 135 women treated on this single arm study , there were two cases of febrile neutropenia ( incidence 1.5 % ) . No patients received RBC transfusion . Darbepoetin alfa therapy was initiated in 92 % of patients . The modest leukocytosis seen during paclitaxel cycles was attributable , in part , to corticosteroid premedication . Other toxicity and dose-delivery were similar to dose-dense AC -- > paclitaxel in Cancer and Leukemia Group B 9741 . CONCLUSION Pegfilgrastim and darbepoetin alfa are effective and safe in facilitating every-2-week AC -- > paclitaxel , minimizing rates of febrile neutropenia and RBC transfusion BACKGROUND Recombinant granulocyte colony-stimulating factors ( G-CSFs ) reduce the incidence and duration of chemotherapy-induced neutropenia and febrile neutropenia when given as adjunct therapy to patients receiving myelosuppressive chemotherapy . Balugrastim is a long-acting G-CSF composed of a genetic fusion between recombinant human serum albumin and G-CSF . We compared the efficacy and safety of balugrastim and pegfilgrastim , a long-acting pegylated recombinant G-CSF , in patients with breast cancer who were scheduled to receive chemotherapy . PATIENTS AND METHODS In this double-blind r and omized phase III trial , patients with ≥ 1.5 × 10(9 ) neutrophils/L were r and omly assigned to subcutaneous injections of balugrastim 40 mg ( n = 153 ) or pegfilgrastim 6 mg ( n = 151 ) . The primary efficacy end point was the duration of severe neutropenia ( DSN ) ( days with an absolute neutrophil count [ ANC ] < 0.5 × 10(9 ) cells/L ) during cycle 1 . Efficacy analyses were performed in the per- protocol ( PP ) population . In a separate open-label single-arm study , newly recruited patients ( n = 77 ) received balugrastim 40 mg and were included in the safety analysis . RESULTS The mean DSN in cycle 1 was 1.1 days in the balugrastim group and 1.0 days in the pegfilgrastim group ( 95 % confidence interval [ CI ] , -0.13 - 0.37 ) . Two and 4 patients , respectively , had febrile neutropenia during cycle 1 . Twenty percent of patients in the balugrastim group and 19 % in the pegfilgrastim group had adverse events ( AEs ) considered to be related to study medication ; 3.9 % and 4.7 % of patients , respectively , experienced serious AEs . CONCLUSIONS This study demonstrates the comparable safety and efficacy profile of balugrastim and pegfilgrastim and the noninferiority of balugrastim for reduction in DSN . There were no unexpected safety events |
1,650 | 22,189,931 | Efficacy trials suggested that nimodipine , transcranial magnetic stimulation , carotid stent placement , and citalopram were effective for VaD. Exploratory studies suggested that white-matter hyperintensities and global vascular risk are predictors of poor response .
Although the low quality of the studies hinders the findings ' generalization , studies of higher validity support the VaD concept for interventions . | OBJECTIVE Vascular depression ( VaD ) hypothesis supports a bidirectional relationship between cerebrovascular risk factors ( CRFs ) and depression .
We examined whether such concept is appropriate for clinical interventions ; i.e. , whether treating depressive symptoms has an impact on cerebrovascular risk and vice-versa . | Background Depression is associated with an increased risk of cardiovascular diseases ( CVD ) in vascular patients as well as in the general population . We investigated whether autonomic dysfunction could explain this relationship . Design The Finl and , Italy and The Netherl and s Elderly ( FINE ) Study is a prospect i ve cohort study . Methods Depressive symptoms were measured with the Zung Self-rating Depression Scale in 870 men , aged 70 - 90 years , free of CVD and diabetes in 1990 . Resting heart rate was determined from a 15 - 30-s resting electrocardiogram in The Netherl and s and Italy and as pulse rate in Finl and . In addition , in The Netherl and s , heart-rate variability ( HRV ) and QTc interval were determined . Results At baseline , depressive symptoms were associated with an increase in resting heart rate , and nonsignificantly with low HRV and prolonged QTc interval . After 10 years of follow-up , 233 ( 27 % ) men died from CVD . Prospect ively , an increase in resting heart rate with 1 SD was associated with an increased risk of cardiovascular mortality [ hazard ratio ( HR ) , 1.22 ; 95 % confidence interval ( CI ) , 1.08 - 1.38 ] . In addition , low HRV ( HR , 0.78 ; 95 % CI , 0.61 - 1.01 ) and prolonged QTc interval ( HR , 1.28 ; 95 % CI , 1.06 - 1.53 ) per SD were associated with cardiovascular mortality . The increased risk of depressive symptoms for cardiovascular mortality ( HR , 1.38 ; 95 % CI , 1.21 - 1.58 ) did not change after adjustments for several indicators of autonomic dysfunction . Conclusion This study suggests that mild depressive symptoms are associated with autonomic dysfunction in elderly men . The increased risk of cardiovascular mortality with increasing magnitude of depressive symptoms could , however , not be explained by autonomic dysfunction . Eur J Cardiovasc Prev Rehabil 14 : 796 - 802 © 2007 The European Society of PURPOSE To prospect ively evaluate if high- grade ( > or = 80 % luminal narrowing ) internal carotid artery stenosis is associated with depressive symptoms and if carotid artery stent placement ( CAS ) potentially improves depressive symptoms . MATERIAL S AND METHODS The study was approved by the local ethics committee , and informed consent was obtained from all subjects . One hundred forty-three patients ( 91 men , 52 women ; interquartile range , 63 - 76 years ) undergoing CAS because of asymptomatic high- grade ( > or = 80 % luminal narrowing ) carotid artery stenosis and 102 control subjects ( 64 men , 38 women ; interquartile range , 63 - 73 years ) with advanced peripheral artery disease and without carotid artery stenosis undergoing lower-limb percutaneous transluminal angioplasty were included . Substantial depressive symptoms ( defined as a Beck Depression Inventory score of 10 or higher ) were recorded at baseline and at 4 weeks ( follow-up ) after the percutaneous procedures . The chi2 test , Mann-Whitney U test , McNemar test , Wilcoxon rank sum test , and two-group t test were used to check for statistical significance . RESULTS A significantly higher prevalence of depressive symptoms was found in patients with carotid artery stenosis than in control subjects with peripheral artery disease at baseline ( 33.6 % vs 16.7 % , P = .003 ) . At follow-up , a significant reduction of depressive symptoms was found in patients who underwent CAS ( 33.6 % vs 9.8 % , P < .001 ) . The frequency of depressive symptoms remained unaffected in control subjects ( 16.7 % vs 13.0 % , P = .1 ) . CONCLUSION High- grade carotid artery stenosis is associated with depressive symptoms in patients with atherosclerosis . CAS seems to exert beneficial effects on the course of depressive symptoms in these patients CONTEXT Research on vascular depression has used 2 approaches to subtype late-life depression , based on executive dysfunction or white matter hyperintensity severity . OBJECTIVE To evaluate the relationship of neuropsychological performance and white matter hyperintensity with clinical response in late-life depression . DESIGN Two-site , prospect i ve , nonr and omized controlled trial . SETTING Outpatient clinics at Washington University and Duke University . PARTICIPANTS A total of 217 subjects aged 60 years or older met DSM-IV criteria for major depression , scored 20 or more on the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and received vascular risk factor scores , neuropsychological testing , and magnetic resonance imaging ; they were excluded for cognitive impairment or severe medical disorders . Fazekas rating was conducted to grade white matter hyperintensity lesions . Intervention Twelve weeks of sertraline treatment , titrated by clinical response . Main Outcome Measure Participants ' MADRS scores over time . RESULTS Baseline neuropsychological factor scores correlated negatively with baseline Fazekas scores . A mixed model examined effects of predictor variables on MADRS scores over time . Baseline episodic memory ( P = .002 ) , language ( P = .007 ) , working memory ( P = .01 ) , processing speed ( P < .001 ) , executive function factor scores ( P = .002 ) , and categorical Fazekas ratings ( P = .05 ) predicted MADRS scores , controlling for age , education , age of onset , and race . Controlling for baseline MADRS scores , these factors remained significant predictors of decrease in MADRS scores , except for working memory and Fazekas ratings . Thirty-three percent of subjects achieved remission ( MADRS < or = 7 ) . Remitters differed from nonremitters in baseline cognitive processing speed , executive function , language , episodic memory , and vascular risk factor scores . CONCLUSIONS Comprehensive neuropsychological function and white matter hyperintensity severity predicted MADRS scores prospect ively over a 12-week treatment course with selective serotonin reuptake inhibitors in late-life depression . Baseline neuropsychological function differentiated remitters from nonremitters and predicted time to remission in a proportional hazards model . Predictor variables correlated highly with vascular risk factor severity . These data support the vascular depression hypothesis and highlight the importance of linking subtypes based on neuropsychological function and white matter integrity . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00045773 Beneficial effects of repetitive transcranial magnetic stimulation ( rTMS ) were demonstrated by many controlled studies in major depression . Moreover , this promising and non invasive therapeutic tool seems to be better tolerated than electroconvulsive therapy CONTEXT The term vascular depression ( VD ) has been used to describe late-life depressive disorders in patients with clinical evidence of cerebrovascular disease . Preliminary data on poststroke depression suggest that repetitive transcranial magnetic stimulation ( rTMS ) might also be effective among patients with VD . OBJECTIVE To examine the efficacy and safety of rTMS to treat VD . DESIGN Prospect i ve , r and omized , sham-controlled study . SETTING University hospital . METHODS After discontinuation of antidepressant therapy , 92 patients with clinical ly defined VD were r and omly assigned to receive active or sham rTMS of the left dorsolateral prefrontal cortex . Approximately half of the patients met criteria for magnetic resonance imaging-defined VD . In experiment 1 , we administered a total cumulative dose ( TCD ) of 12 000 pulses ( TCD-12 K ) ; in experiment 2 , 18,000 pulses ( TCD-18 K ) . Sham stimulation was performed using a sham coil . RESULTS In experiment 1 , the sham group showed a 13.6 % decrease in the 17-item Hamilton Depression Rating Scale ( HAMD-17 ) scores compared with a 33.1 % decrease in the TCD-12 K group ( P = .04 ) . Response rates were 6.7 % in the sham group and 33.3 % in the active-stimulation group ( P = .08 ) ; remission rates were 6.7 % and 13.3 % , respectively ( P = .50 ) . In experiment 2 , the sham group showed a 17.5 % decrease in the 17-item Hamilton Depression Rating Scale scores compared with a 42.4 % decrease observed in the TCD-18 K group ( P < .001 ) . Response rates were 6.9 % in the sham group and 39.4 % in the active-stimulation group ( P = .003 ) ; remission rates were 3.5 % and 27.3 % , respectively ( P = .01 ) . Response rates to rTMS were negatively correlated with age and positively correlated with higher frontal gray matter volumes . CONCLUSIONS To our knowledge , this is the first controlled trial that demonstrates the efficacy of rTMS among geriatric patients with VD . Older age and smaller frontal gray matter volumes were associated with a poorer response to rTMS OBJECTIVES The authors previously reported that repetitive transcranial magnetic stimulation ( rTMS ) produced a response rate of 39.4 % among 62 patients with treatment resistant vascular depression . This study was undertaken to assess the outcome of continuation therapy to prevent relapse among these patients during 9 weeks after completion of rTMS . DESIGN Patients were r and omly assigned to 18,000 pulses of rTMS given over 3 weeks or sham treatment using double blind methods . After rTMS , all patients were given 20 mg/day of citalopram for 9 weeks and reevaluated at 3 , 6 , and 9 weeks . SETTING Outpatient continuation treatment trial . PARTICIPANTS Patients with vascular depression ( N = 62 ) , as determined by magnetic resonance imaging hyperintensities and three or more clinical risk factors for vascular disease without other major medical illness , were recruited . They had onset of major depression after age 50 and failed at least one trial of antidepressants . INTERVENTION After rTMS or sham treatment , all treatment responders were given citalopram for 9 weeks . RESULTS Among the 33 patients who were given rTMS , 13 responded ( i.e. , > 50 % decline in Hamilton Depression Scale score ) . Of these 13 , all completed the 9 weeks of continuation treatment . There were nine patients who continued to be responders and four who had a relapse of depression . CONCLUSION More effective methods are needed to treat elderly patients with treatment resistant vascular depression and to prevent relapse among treatment responders BACKGROUND Vascular depression has been proposed as a unique diagnostic subtype in late life , yet no study has evaluated whether the specified clinical features associated with the illness are jointly indicative of an underlying diagnostic class . METHODS We applied latent class analysis to two independent clinical sample s : the prospect i ve , cohort design , Neurocognitive Outcomes of Depression in the Elderly ( NCODE ) study and the 8-week , multicenter , double blind , placebo-controlled Old-Old study . RESULTS A two-class model consisting of vascular and nonvascular depressed patients provided an excellent fit to the data in both studies , chi(2)(6 ) = 2.02 , p = .90 in the NCODE study and chi(2)(6 ) = 7.024 , p = .32 in the Old-Old study . Although all of the proposed features of vascular depression were useful in identifying the illness , deep white matter lesion burden emerged with perfect sensitivity ( 1.00 ) and near-perfect specificity ( .95 ) , making it the only indicator necessary to determine class membership . CONCLUSIONS These findings , replicated across two independent clinical sample s , provide the first support for the internal validity of vascular depression as a subtype of late-life depression BACKGROUND ' Vascular depression ' may be caused by cerebrovascular disease . Calcium channel blockers , which are putative treatments for cerebrovascular disease , might be expected to improve depression reduction and to prevent recurrence of depression in this patient population . This clinical trial was design ed to test these hypotheses . DESIGN This was a controlled , double blind , r and omized clinical trial in which 84 patients with vascular depression ( Alexopoulos criteria ) were treated with antidepressants at st and ard doses . Patients were also r and omized to nimodipine ( n = 40 ) or an inactive comparator , vitamin C ( n = 44 ) . Treatment outcomes were assessed using the Hamilton depression rating scale ( HDRS ) regularly up to 300 days after treatment initiation . RESULTS As expected , depression reduction was successful in most patients . In addition , those treated with nimodipine plus an antidepressant had greater improvements in depression overall in repeated measures ANCOVA ( F(1,81 ) = 8.64 , p = 0.004 ) . As well a greater proportion of nimodipine-treated participants ( 45 versus 25 % ) exhibited a full remission ( HDRS < or = 10 ) ( chi(2)(df , 1 ) = 3.71 , p = 0.054 ) . Among those experiencing a substantial response in the first 60 days ( 50 % reduction in HDRS ) , fewer patients on nimodipine ( 7.4 % ) had a recurrence of major depression when compared to those on antidepressant alone ( 32 % ) ( chi(2)(df , 1 ) = 3.59 , p = 0.058 ) . CONCLUSIONS In treating vascular depression , augmentation of antidepressant therapy with a calcium-channel blocker leads to greater depression reduction and lower rates of recurrence . These findings support the argument that cerebrovascular disease is involved in the pathogenesis and recurrence of depression in these patients OBJECTIVE There is increasing evidence that cerebrovascular factors play a key role in the etiology of late-life depression . This study examined the severity of subcortical hyperintensities ( SH ) and the relationship between SH and depression characteristics in two sample s of elderly depressed out patients differing in age . METHODS The sample s consisted of 59 subjects age 60 and over , ( 69+/-5.6 years ) , who participated in a trial of sertraline , and 111 subjects age 75 and over , ( 79+/-4.1 years ) , who participated in a trial of citalopram . RESULTS The citalopram group was significantly older than the sertraline group and had more severe SH ( 72 % vs. 42 % high ratings ) . The High SH group was significantly older than the Low SH group in the sertraline study but there was no difference in age in the SH groups in the citalopram sample . There was no relationship between SH severity and baseline depression or age of onset . However , age strongly correlated with later age of onset . There was no relationship between SH severity and cardiovascular risk factors or treatment response in the sertraline sample . CONCLUSION Age is a major factor for the development of SH and late-life depression . There may not be an association between SH and depression severity , cardiovascular risk factors , or treatment response in geriatric depressed out patients . The etiologic factors and clinical course of late-life depression requires further study BACKGROUND Cerebrovascular disease may cause " vascular depression " ( VaD ) . Calcium channel-blockers are presumed treatments for cerebrovascular disease and might be expected to improve depression and prevent recurrence . OBJECTIVE To examine the efficacy and tolerability of the use of nimodipine as an augmentation of fluoxetine in the treatment of VaD. DESIGN A double-blind , r and omized clinical trial in which 101 patients with VaD ( Alexopoulos criteria ) were treated with fluoxetine at st and ard doses . Patients were r and omized to placebo ( n=51 ) or nimodipine ( n=50 ) . Treatment outcomes were assessed using the Hamilton Depression Rating Scale ( HDRS ) regularly up to 8 months after treatment initiation . RESULTS Depression was reduced in 63 % of patients , but those whose treatment was enhanced with nimodipine had greater improvements overall by repeated measures analysis of covariance ( ANCOVA ) ( F(1.80 ) = 9.76 , p=0.001 ) . In addition , a greater proportion of patients treated with fluoxetine-nimodipine ( 54 % vs. 27 % ) exhibited full remission ( chi2(d.f . 1)= 7.3 , p = 0.006 ) , with the number needed to treat ( NNT ) equal to 4 ( 95 % CI 2 - 12 ) . Of those experiencing full remission in the first 61 days , fewer patients on fluoxetine-nimodipine ( 3.7 % ) developed recurrence of major depression as compared to those on fluoxetine alone ( 35.7 % ) ( chi2(d.f . 1 ) = 7.56 , p = 0.006 ) , NNT 3 ( 95 % CI 2 - 9 ) . Side-effects were noted in 33.3 % of patients in the control group and 48 % of the experimental group ( chi2(d.f . 1 ) = 2.25 , p = 0.133 ) . CONCLUSIONS In treating VaD , augmentation of fluoxetine with nimodipine led to better treatment results and lower rates of recurrence . These findings support the argument that augmentation of antidepressant therapy might be helpful in the treatment of cerebrovascular disease , which is involved in the pathogenesis of this type of depression Repetitive transcranial magnetic stimulation ( rTMS ) is an effective treatment for depression . Increased metabolism in the anterior cingulate cortex ( ACC ) is a known predictor for antidepressant response . The authors assessed whether increased theta power within the ACC predicts rTMS response in participants with vascular depression . Sixty-five participants were r and omized to active or sham rTMS . Outcome was assessed using the Hamilton Depression Rating Scale . Electroencephalography was obtained , and comparisons were made among each group with a normative data base using low-resolution electromagnetic tomography . Results suggest that vascular depression participants respond well to rTMS and that increased low-theta power in the subgenual ACC predicts response to rTMS |
1,651 | 26,733,670 | Conclusions Patients with OAC and TP53 gene mutations have reduced overall survival compared with patients without these mutations , and this effect is independent of tumour stage | Objective To clarify the prognostic role of tumour protein 53 ( TP53 ) mutations in patients with oesophageal adenocarcinoma ( OAC ) as there is a need for biomarkers that assist in guiding management for patients with OAC . | Despite years of research and hundreds of reports on tumor markers in oncology , the number of markers that have emerged as clinical ly useful is pitifully small . Often , initially reported studies of a marker show great promise , but subsequent studies on the same or related markers yield inconsistent conclusions or st and in direct contradiction to the promising results . It is imperative that we attempt to underst and the reasons that multiple studies of the same marker lead to differing conclusions . A variety of method ologic problems have been cited to explain these discrepancies . Unfortunately , many tumor marker studies have not been reported in a rigorous fashion , and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results . The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer ( NCI-EORTC ) First International Meeting on Cancer Diagnostics in 2000 . As for the successful CONSORT initiative for r and omized trials and for the STARD statement for diagnostic studies , we suggest guidelines to provide relevant information about the study design , preplanned hypotheses , patient and specimen characteristics , assay methods , and statistical analysis methods . In addition , the guidelines suggest helpful presentations of data and important elements to include in discussion s. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and underst and the context in which the conclusions apply Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Significance Whole-exome sequencing ( WES ) is gradually being optimized to identify mutations in increasing proportions of the protein-coding exome , but whole-genome sequencing ( WGS ) is becoming an attractive alternative . WGS is currently more expensive than WES , but its cost should decrease more rapidly than that of WES . We compared WES and WGS on six unrelated individuals . The distribution of quality parameters for single-nucleotide variants ( SNVs ) and insertions/deletions ( indels ) was more uniform for WGS than for WES . The vast majority of SNVs and indels were identified by both techniques , but an estimated 650 high- quality coding SNVs ( ∼3 % of coding variants ) were detected by WGS and missed by WES . WGS is therefore slightly more efficient than WES for detecting mutations in the targeted exome . We compared whole-exome sequencing ( WES ) and whole-genome sequencing ( WGS ) in six unrelated individuals . In the regions targeted by WES capture ( 81.5 % of the consensus coding genome ) , the mean numbers of single-nucleotide variants ( SNVs ) and small insertions/deletions ( indels ) detected per sample were 84,192 and 13,325 , respectively , for WES , and 84,968 and 12,702 , respectively , for WGS . For both SNVs and indels , the distributions of coverage depth , genotype quality , and minor read ratio were more uniform for WGS than for WES . After filtering , a mean of 74,398 ( 95.3 % ) high- quality ( HQ ) SNVs and 9,033 ( 70.6 % ) HQ indels were called by both platforms . A mean of 105 coding HQ SNVs and 32 indels was identified exclusively by WES whereas 692 HQ SNVs and 105 indels were identified exclusively by WGS . We Sanger-sequenced a r and om selection of these exclusive variants . For SNVs , the proportion of false-positive variants was higher for WES ( 78 % ) than for WGS ( 17 % ) . The estimated mean number of real coding SNVs ( 656 variants , ∼3 % of all coding HQ SNVs ) identified by WGS and missed by WES was greater than the number of SNVs identified by WES and missed by WGS ( 26 variants ) . For indels , the proportions of false-positive variants were similar for WES ( 44 % ) and WGS ( 46 % ) . Finally , WES was not reliable for the detection of copy-number variations , almost all of which extended beyond the targeted regions . Although currently more expensive , WGS is more powerful than WES for detecting potential disease-causing mutations within WES regions , particularly those due to SNVs BACKGROUND Data from observational studies suggest that body mass index ( BMI ) is causally related to esophageal adenocarcinoma ( EAC ) and its precursor , Barrett 's esophagus ( BE ) . However , the relationships may be affected by bias and confounding . METHODS We used data from the Barrett 's and Esophageal Adenocarcinoma Genetic Susceptibility Study : 999 patients with EAC , 2061 patients with BE , and 2169 population controls . We applied the two-stage control function instrumental variable method of the Mendelian r and omization approach to estimate the unbiased , unconfounded effect of BMI on risk of EAC and BE . This was performed using a genetic risk score , derived from 29 genetic variants shown to be associated with BMI , as an instrument for lifetime BMI . A higher score indicates propensity to obesity . All tests were two-sided . RESULTS The genetic risk score was not associated with potential confounders , including gastroesophageal reflux symptoms and smoking . In the instrumental variable analyses ( IV ) , EAC risk increased by 16 % ( IV-odds ratio [ OR ] = 1.16 , 95 % confidence interval [ CI ] = 1.01 to 1.33 ) and BE risk increased by 12 % ( IV-OR = 1.12 , 95 % CI = 1.00 to 1.25 ) per 1kg/m(2 ) increase in BMI . BMI was statistically significantly associated with EAC and BE in conventional epidemiologic analyses . CONCLUSIONS People with a high genetic propensity to obesity have higher risks of esophageal metaplasia and neoplasia than people with low genetic propensity . These analyses provide the strongest evidence to date that obesity is independently associated with BE and EAC , and is not due to confounding or bias inherent in conventional epidemiologic analyses BACKGROUND The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established . We compared chemoradiotherapy followed by surgery with surgery alone in this patient population . METHODS We r and omly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin ( doses titrated to achieve an area under the curve of 2 mg per milliliter per minute ) and paclitaxel ( 50 mg per square meter of body-surface area ) for 5 weeks and concurrent radiotherapy ( 41.4 Gy in 23 fractions , 5 days per week ) , followed by surgery . RESULTS From March 2004 through December 2008 , we enrolled 368 patients , 366 of whom were included in the analysis : 275 ( 75 % ) had adenocarcinoma , 84 ( 23 % ) had squamous-cell carcinoma , and 7 ( 2 % ) had large-cell undifferentiated carcinoma . Of the 366 patients , 178 were r and omly assigned to chemoradiotherapy followed by surgery , and 188 to surgery alone . The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia ( 6 % ) and neutropenia ( 2 % ) ; the most common major nonhematologic toxic effects were anorexia ( 5 % ) and fatigue ( 3 % ) . Complete resection with no tumor within 1 mm of the resection margins ( R0 ) was achieved in 92 % of patients in the chemoradiotherapy-surgery group versus 69 % in the surgery group ( P<0.001 ) . A pathological complete response was achieved in 47 of 161 patients ( 29 % ) who underwent resection after chemoradiotherapy . Postoperative complications were similar in the two treatment groups , and in-hospital mortality was 4 % in both . Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group . Overall survival was significantly better in the chemoradiotherapy-surgery group ( hazard ratio , 0.657 ; 95 % confidence interval , 0.495 to 0.871 ; P=0.003 ) . CONCLUSIONS Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer . The regimen was associated with acceptable adverse-event rates . ( Funded by the Dutch Cancer Foundation [ KWF Kankerbestrijding ] ; Netherl and s Trial Register number , NTR487 . ) The incidence of adenocarcinomas in Barrett 's esophagus has been rising in the last two decades in the United States and Western Europe for yet unknown reasons . We reported previously a large multi-institutional trial implicating p53 mutations as being involved in the pathogenesis of Barrett 's cancer and representing an early marker for the malignant potential of Barrett 's epithelium . A prospect i ve study was performed to evaluate the prognostic impact of p53 mutations on survival in 59 patients with Barrett 's cancer . Tissue for DNA analysis was obtained by endoscopic biopsy or immediately after surgical resections from the tumor , Barrett 's epithelium , and normal stomach and esophagus . p53 mutation analysis was performed by PCR-single str and conformational polymorphism screening of exons 5 - 9 and DNA sequencing to unequivocally prove the presence of a mutation . p53 mutations were identified in 30 of 59 ( 50.8 % ) patients . The presence of a p53 mutation in the tumor had a significant impact on survival after curative resections ( RO-resections ) with cumulative 5-year survival probabilities of 68.8+/-9.7 % for mutation-negative tumors and 24.3+/-9.9 % for mutation-positive tumors ( log rank : P < 0.001 ) . By Cox proportional hazard analysis , including the parameters of gender , age , Union International Contre Cancer tumor stage , grading , and p53 mutation status , only Union International Contre Cancer tumor stage ( P < 0.0001 ) and p53 mutation status ( P < 0.02 ) were of significant independent prognostic importance . p53 mutation analysis by DNA sequencing is of significant independent prognostic importance next to histopathological tumor stage in patients with curatively resected ( RO-resection ) Barrett 's cancer . It appears that p53 mutational status is a valuable parameter to define low-risk ( p53 mutation-negative ) and high-risk ( p53 mutation-positive ) groups for treatment failure after curative resections BACKGROUND Fluorouracil and cisplatin have been used most frequently as neoadjuvant therapy for esophageal cancer . Both drugs are believed to act via a p53-dependent apoptosis pathway . The TP53 gene is frequently mutated in esophageal cancer . OBJECTIVE To test the value of TP53 as a biomarker prognosing outcome in patients with neoadjuvantly treated esophageal cancer . PATIENTS AND METHODS The investigation included 36 patients with primary operable esophageal cancer who were treated neoadjuvantly with cisplatin and fluorouracil . The TP53 genotype was assessed from paraffin-embedded diagnostic tumor biopsies using a st and ardized gene-specific TP53 sequencing protocol ( mark53 kit ; mark53 Ltd , Vienna , Austria ) . RESULTS Mutations in the TP53 gene were present in 50 % of tumors . Two-year overall survival rates were 55.6 % in patients with a normal TP53 marker status , compared with 16.7 % in those with a mutant TP53 gene . In patients with normal TP53 , neoadjuvant treatment result ed in significant advantages in terms of tumor-associated survival ( P=.0049 ) and overall survival ( P=.0304 ) compared with those with mutant TP53 . The median tumor-associated survival was 34.2 months for patients with normal TP53 , compared with 8.9 months for those with mutant TP53 . The latter had a 3-fold higher risk of dying ( hazard ratio , 3.01 ; 95 % confidence interval , 1.359 - 6.86 ) . CONCLUSIONS The biomarker TP53 divides esophageal cancer patients into 2 categories with markedly different outcomes : patients with a normal TP53 marker status may experience notable benefits from neoadjuvant chemotherapy with cisplatin/fluorouracil , whereas those with a mutant TP53 marker status appear to be at risk for lack of response |
1,652 | 29,484,554 | IREE had improved diagnostic odds ratio , sensitivity , and identification rate compared to NIFI .
Conclusions We found encouraging results regarding the accuracy , diagnostic odds ratio , and specificity of the test .
The sensitivity was not optimal but may be improved by a strict protocol to augment the technique . | Background Sentinel node navigation surgery ( SNNS ) for gastric cancer using infrared visualization of indocyanine green ( ICG ) is intriguing because it may limit operative morbidity .
We are the first to systematic ally review and perform meta- analysis on the diagnostic utility of ICG and infrared electronic endoscopy ( IREE ) or near infrared fluorescent imaging ( NIFI ) for SNNS exclusively in gastric cancer . | Abstract The clinical application of sentinel node biopsies in early gastric cancer is still controversial even though it appears promising . This study was conducted as a prerequisite quality control for surgical st and ardization of laparoscopic sentinel basin dissection ( SBD ) prior to the initiation of a phase III trial . Laparoscopic SBD was performed in patients with preoperative stage T1 - 2N0 and tumor size < 4 cm in diameter . Intraoperative endoscopic submucosal injection of a st and ardized dual tracer was administered . All retrieved sentinel basin nodes ( SBN ) were investigated with intraoperative frozen hematoxylin and eosin ( H&E ) staining . A strict checklist consisting of 7 essential steps was followed during laparoscopic SBD as the quality control study for a phase III trial . Completion of all essential steps in the checklist for 10 cases was used to define a qualified institution . Seven institutions participated and 112 patients were enrolled in this study . However , 4 patients were excluded owing to screening failure . The mean number of cases required for institutional qualification was 15 cases ( range , 13–20 cases ) . Sentinel basins ( SB ) were detected and dissected in 100 of the 108 patients ( 92.6 % ) ; the median number of SB and SBN was 2 and 7 , respectively . Lymph node metastases were detected in 10 patients by postoperative permanent H&E staining and they were detected by SBD in all 10 patients . Frozen results of SBN were compatible with permanent staining reports . Laparoscopic SBD is feasible and demonstrated improved sensitivity in detecting metastatic lymph nodes compared to the previous study . A future phase III r and omized trial comparing laparoscopic SBD with organ-preserving gastrectomy and laparoscopic st and ard gastrectomy seems promising for qualified institutions AIM To investigate feasibility and accuracy of near-infrared fluorescence imaging using indocyanine green : nanocolloid for sentinel lymph node ( SLN ) detection in gastric cancer . METHODS A prospect i ve , single-institution , phase I feasibility trial was conducted . Patients suffering from gastric cancer and planned for gastrectomy were included . During surgery , a subserosal injection of 1.6 mL ICG : Nanocoll was administered around the tumor . NIR fluorescence imaging of the abdominal cavity was performed using the Mini-FLARE ™ NIR fluorescence imaging system . Lymphatic pathways and SLNs were visualized . Of every detected SLN , the corresponding lymph node station , signal-to- background ratio and histopathological diagnosis was determined . Patients underwent st and ard-of-care gastrectomy . Detected SLNs outside the st and ard dissection planes were also resected and evaluated . RESULTS Twenty-six patients were enrolled . Four patients were excluded because distant metastases were found during surgery or due to technical failure of the injection . In 21 of the remaining 22 patients , at least 1 SLN was detected by NIR Fluorescence imaging ( mean 3.1 SLNs ; range 1 - 6 ) . In 8 of the 21 patients , tumor-positive LNs were found . Overall accuracy of the technique was 90 % ( 70%-99 % ; 95%CI ) , which decreased by higher pT-stage ( 100 % , 100 % , 100 % , 90 % , 0 % for respectively Tx , T1 , T2 , T3 , T4 tumors ) . All NIR-negative SLNs were completely effaced by tumor . Mean fluorescence signal-to- background ratio of SLNs was 4.4 ( range 1.4 - 19.8 ) . In 8 of the 21 patients , SLNs outside the st and ard resection plane were identified , that contained malignant cells in 2 patients . CONCLUSION This study shows successful use of ICG : Nanocoll as lymphatic tracer for SLN detection in gastric cancer . Moreover , tumor-containing LNs outside the st and ard dissection planes were identified Background Prospect i ve multicenter trials have shown the feasibility of sentinel node ( SN ) navigation surgery using a dual tracer of dye and radioisotope for early gastric cancer . However , comparable trials using the indocyanine green ( ICG ) and the infrared ray laparoscopic system ( IRLS ) have not been reported . On the basis of our cohort studies , we assumed that the ICG imaging with the IRLS is as effective as the dual tracer in detecting SNs . Therefore , we conducted a prospect i ve multicenter trial to assess the effectiveness and generalizability of the infrared ICG technique in patients with early gastric cancer . Patients and methods Patients with previously untreated cT1 gastric adenocarcinomas less than 4 cm in gross diameter were eligible for inclusion in this study . SN mapping was performed by using ICG combined with IRLS technique . Following biopsy of the identified SNs , D2 or modified D2 laparoscopic gastrectomy was performed according to the current Japanese Gastric Cancer Association guidelines . Results Among the 47 patients who gave written informed consent , 44 were eligible from the surgical findings , for whom SN biopsy was performed . The detection rate of the lymphatic basin by the ICG with IRLS was 100 % ( 44/44 ) . The accuracy was also 100 % ( 7/7 ) for detecting metastatic lymph node , which was verified on the permanent pathologic examination . Following the median follow-up of 114 months ( range , 60 to 120 months ) , no recurrence ( 0/40 ) was observed . Although the number of patients was unequally distributed among the hospitals participating in the trial , the detection rates of SNs in low-volume hospitals were comparable to those in high-volume hospitals . Consequently , there was no learning curve in this trial . Conclusion The infrared ICG imaging accurately detected the lymphatic basin and SNs with occult metastasis in SN-navigated gastrectomy for gastric cancer . This method was feasible even for low-volume surgeons and hospitals More than ten years have passed since the sentinel node ( SN ) concept for gastric cancer surgery was first discussed . Less invasive modified surgical approaches based on the SN concept have already been put into practice for malignant melanoma and breast cancer , however the SN concept is not yet placed in a st and ard position in gastric cancer surgery even after two multi-institutional prospect i ve clinical trials , the Japan Clinical Oncology Group trial ( JCOG0302 ) and the Japanese Society for Sentinel Node Navigation Surgery ( SNNS ) trial . What is the problem in the clinical application of the SN concept to gastric cancer surgery ? There is no doubt that we need reliable indicator(s ) to determine with certainty the absence of metastasis in the lymph nodes in order to avoid unnecessary lymphadenectomy . There are several matters of debate in performing the actual procedure , such as the type of tracer , the site of injection , how to detect and harvest , how to detect metastases of SNs , and learning period . These issues have to be addressed further to establish the most suitable procedure . Novel technologies such as indocyanine green ( ICG ) fluorescence imaging and one-step nucleic acid amplification ( OSNA ) may overcome the current difficulties . Once we know what the problems are and how to tackle them , we can pursue the goal Background Along with the marked increase in early gastric cancer ( EGC ) in the Eastern countries , there has been an effort to adopt the sentinel node concept in EGC to preserve gastric function and reduce the occurrence of postoperative complications . Based on promising results from a previous quality control study , this prospect i ve multicenter r and omized controlled phase III clinical trial aims to eluci date the oncologic safety of laparoscopic stomach-preserving surgery with sentinel basin dissection ( SBD ) compared to a st and ard laparoscopic gastrectomy . Methods / Design This trial is an investigator-initiated , open-label , multicenter r and omized controlled phase III trial with a non-inferiority design . Patients diagnosed with a single lesion of clinical stage T1N0M0 gastric adenocarcinoma , with a diameter of 3 cm or less are eligible for the present study . A total of 580 patients ( 290 per group ) will be r and omized to either laparoscopic stomach-preserving surgery with SBD or st and ard surgery . The primary end-point is 3-year disease-free survival ( DFS ) and the secondary endpoints include postoperative morbidity and mortality , quality of life , 5-year DFS , and overall survival . Qualified investigators who completed the prior quality control study are exclusively allowed to participate in this phase III clinical trial . Discussion The proposed trial is expected to verify whether laparoscopic stomach-preserving surgery with SBD achieves similar oncologic outcomes and improved quality of life compared to a st and ard gastrectomy in EGC patients .Trial registration This study was registered at the NIH Clinical Trial.gov data base ( NCT01804998 ) on March 4th , 2013 BACKGROUND Examination of at least 16 lymph nodes ( LNs ) has been traditionally recommended during gastric adenocarcinoma resection to optimize staging , but the impact of this strategy on survival is uncertain . Because recent r and omized trials have demonstrated a therapeutic benefit from extended lymphadenectomy , we sought to investigate the impact of the number of LNs removed on prognosis after gastric adenocarcinoma resection . STUDY DESIGN We analyzed patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012 , at 7 US academic institutions . Patients with M1 disease or R2 resections were excluded . Disease-specific survival ( DSS ) was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses . RESULTS Of 742 patients , 257 ( 35 % ) had 7 to 15 LNs removed and 485 ( 65 % ) had ≥16 LNs removed . Disease-specific survival was not significantly longer after removal of ≥16 vs 7 to 15 LNs ( 10-year survival , 55 % vs 47 % , respectively ; p = 0.53 ) for the entire cohort , but was significantly improved in the subset of patients with stage IA to IIIA ( 10-year survival , 74 % vs 57 % , respectively ; p = 0.018 ) or N0 - 2 disease ( 72 % vs 55 % , respectively ; p = 0.023 ) . Similarly , for patients who were classified to more likely be " true N0 - 2 , " based on frequentist analysis incorporating both the number of positive and of total LNs removed , the hazard ratio for disease-related death ( adjusted for T stage , R status , grade , receipt of neoadjuvant and adjuvant therapy , and institution ) significantly decreased as the number of LNs removed increased . CONCLUSIONS The number of LNs removed during gastrectomy for adenocarcinoma appears itself to have prognostic implication s for long-term survival BACKGROUND The survival benefit and morbidity after nodal dissection for gastric cancer remains controversial . We aim ed to do a single-institution r and omised trial to compare D1 ( ie , level 1 ) lymphadenectomy with that of D3 ( ie , levels 1 , 2 , and 3 ) dissection for gastric cancer in terms of overall survival and disease-free survival . METHODS From Oct 7 , 1993 , to Aug 12 , 1999 , 335 patients were registered . 221 patients were eligible , 110 of whom were r and omly assigned D1 surgery and 111 of whom were r and omly assigned D3 surgery , both with curative intent . Three participating surgeons had done at least 25 independent D3 dissections before the start of the trial , and every procedure was verified by pathological analyses . The primary endpoints were 5-year overall survival and 5-year disease-free survival . We also analysed risk of recurrence . Main analyses were done by intention to treat . This trial is registered at the US National Institute of Health website . FINDINGS Median follow-up for the 110 ( 50 % ) survivors was 94.5 months ( range 62.9 - 135.1 ) . Overall 5-year survival was significantly higher in patients assigned D3 surgery than in those assigned D1 surgery ( 59.5 % [ 95 % CI 50.3 - 68.7 ] vs 53.6 % [ 44.2 - 63.0 ] ; difference beteween groups 5.9 % [ -7.3 to 19.1 ] , log-rank p=0.041 ) . 215 patients who had R0 resection ( ie , no microscopic evidence of residual disease ) had recurrence at 5 years of 50.6 % [ 41.1 - 60.2 ] for D1 surgery and 40.3 % [ 30.9 - 49.7 ] for D3 surgery ( difference between groups 10.3 % [ -3.2 to 23.7 ] , log-rank p=0.197 ) . INTERPRETATION D3 nodal dissection , compared with that of D1 , offers a survival benefit for patients with gastric cancer when done by well trained , experienced surgeons BACKGROUND Historical data and recent studies show that st and ardised extended ( D2 ) lymphadenectomy leads to better results than st and ardised limited ( D1 ) lymphadenectomy . Based on these findings , the Dutch D1D2 trial , a nationwide prospect ively r and omised clinical trial , was undertaken to compare D2 with D1 lymphadenectomy in patients with resectable primary adenocarcinoma of the stomach . The aim of the study was to assess the effect of D2 compared with D1 surgery on disease recurrence and survival in patients treated with curative intent . METHODS Between August , 1989 , and July , 1993 , patients were entered and r and omised at 80 participating hospitals by means of a telephone call to the central data centre of the trial . The sequence of r and omisation was in blocks of six with stratification for the participating centre . Eligibility criteria were a histologically proven adenocarcinoma of the stomach without evidence of distance metastasis , age younger than 85 years , and adequate physical condition for D1 or D2 lymphadenectomy . Patients were excluded if they had previous or coexisting cancer or had undergone gastrectomy for benign tumours . Strict quality control measures for pathological assessment were implemented and monitored . Analyses were by intention to treat . This study is registered with the NCI trial register , as DUT-KWF-CKVO-8905 , EU-90003 . FINDINGS A total of 1078 patients were entered in the study , of whom 996 were eligible . 711 patients underwent the r and omly assigned treatment with curative intent ( 380 in the D1 group and 331 in the D2 group ) and 285 had palliative treatment . Data were collected prospect ively and all patients were followed up for a median time of 15.2 years ( range 6.9 - 17.9 years ) . Analyses were done for the 711 patients treated with curative intent and were according to the allocated treatment group . Of the 711 patients , 174 ( 25 % ) were alive , all but one without recurrence . Overall 15-year survival was 21 % ( 82 patients ) for the D1 group and 29 % ( 92 patients ) for the D2 group ( p=0.34 ) . Gastric-cancer-related death rate was significantly higher in the D1 group ( 48 % , 182 patients ) compared with the D2 group ( 37 % , 123 patients ) , whereas death due to other diseases was similar in both groups . Local recurrence was 22 % ( 82 patients ) in the D1 group versus 12 % ( 40 patients ) in D2 , and regional recurrence was 19 % ( 73 patients ) in D1 versus 13 % ( 43 patients ) in D2 . Patients who had the D2 procedure had a significantly higher operative mortality rate than those who had D1 ( n=32 [ 10 % ] vs n=15 [ 4 % ] ; 95 % CI for the difference 2 - 9 ; p=0.004 ) , higher complication rate ( n=142 [ 43 % ] vs n=94 [ 25 % ] ; 11 - 25 ; p<0.0001 ) , and higher reoperation rate ( n=59 [ 18 % ] vs n=30 [ 8 % ] ; 5 - 15 ; p=0.00016 ) . INTERPRETATION After a median follow-up of 15 years , D2 lymphadenectomy is associated with lower locoregional recurrence and gastric-cancer-related death rates than D1 surgery . The D2 procedure was also associated with significantly higher postoperative mortality , morbidity , and reoperation rates . Because a safer , spleen-preserving D2 resection technique is currently available in high-volume centres , D2 lymphadenectomy is the recommended surgical approach for patients with resectable ( curable ) gastric cancer . FUNDING Dutch Health Insurance Funds Council and The Netherl and s Cancer Foundation PURPOSE Complicated gastric lymphatic drainage potentially undermines the utility of sentinel node ( SN ) biopsy in patients with gastric cancer . Encouraged by several favorable single-institution reports , we conducted a multicenter , single-arm , phase II study of SN mapping that used a st and ardized dual tracer endoscopic injection technique . PATIENTS AND METHODS Patients with previously untreated cT1 or cT2 gastric adenocarcinomas < 4 cm in gross diameter were eligible for inclusion in this study . SN mapping was performed by using a st and ardized dual tracer endoscopic injection technique . Following biopsy of the identified SNs , m and atory comprehensive D2 or modified D2 gastrectomy was performed according to current Japanese Gastric Cancer Association guidelines . RESULTS Among 433 patients who gave preoperative consent , 397 were deemed eligible on the basis of surgical findings . SN biopsy was performed in all patients , and the SN detection rate was 97.5 % ( 387 of 397 ) . Of 57 patients with lymph node metastasis by conventional hematoxylin and eosin staining , 93 % ( 53 of 57 ) had positive SNs , and the accuracy of nodal evaluation for metastasis was 99 % ( 383 of 387 ) . Only four false-negative SN biopsies were observed , and pathologic analysis revealed that three of those biopsies were pT2 or tumors > 4 cm . We observed no serious adverse effects related to endoscopic tracer injection or the SN mapping procedure . CONCLUSION The endoscopic dual tracer method for SN biopsy was confirmed as safe and effective when applied to the superficial , relatively small gastric adenocarcinomas included in this study |
1,653 | 29,416,382 | Conclusion HIIT is superior to MICT in improving cardiorespiratory fitness in participants of cardiac rehabilitation ( CR ) .
Improvements in cardiorespiratory fitness are significant for CR programs of > 6-week duration .
Programs of 7 - 12 weeks ' duration result ed in the largest improvements in cardiorespiratory fitness for patients with coronary artery disease .
HIIT appears to be as safe as MICT for CR participants | Background Aerobic capacity has been shown to be inversely proportionate to cardiovascular mortality and morbidity and there is growing evidence that high-intensity interval training ( HIIT ) appears to be more effective than moderate-intensity continuous training ( MICT ) in improving cardiorespiratory fitness within the cardiac population .
Previously published systematic review s in cardiovascular disease have neither investigated the effect that the number of weeks of intervention has on cardiorespiratory fitness changes , nor have adverse events been collated .
Objective We aim ed to undertake a systematic review and meta- analysis of r and omized controlled trials ( RCTs ) within the cardiac population that investigated cardiorespiratory fitness changes result ing from HIIT versus MICT and to collate adverse events . | The oxygen uptake efficiency slope ( OUES ) is a submaximal index incorporating cardiovascular , peripheral , and pulmonary factors that determine the ventilatory response to exercise . The purpose of this study was to evaluate the effects of continuous exercise training and interval exercise training on the OUES in patients with coronary artery disease . Thirty-five patients ( 59.3±1.8 years old ; 28 men , 7 women ) with coronary artery disease were r and omly divided into two groups : continuous exercise training ( n=18 ) and interval exercise training ( n=17 ) . All patients performed grade d exercise tests with respiratory gas analysis before and 3 months after the exercise-training program to determine ventilatory anaerobic threshold ( VAT ) , respiratory compensation point , and peak oxygen consumption ( peak VO2 ) . The OUES was assessed based on data from the second minute of exercise until exhaustion by calculating the slope of the linear relation between oxygen uptake and the logarithm of total ventilation . After the interventions , both groups showed increased aerobic fitness ( P<0.05 ) . In addition , both the continuous exercise and interval exercise training groups demonstrated an increase in OUES ( P<0.05 ) . Significant associations were observed in both groups : 1 ) continuous exercise training ( OUES and peak VO2 r=0.57 ; OUES and VO2 VAT r=0.57 ) ; 2 ) interval exercise training ( OUES and peak VO2 r=0.80 ; OUES and VO2 VAT r=0.67 ) . Continuous and interval exercise training result ed in a similar increase in OUES among patients with coronary artery disease . These findings suggest that improvements in OUES among CAD patients after aerobic exercise training may be dependent on peripheral and central mechanisms BACKGROUND Peak oxygen uptake ( Vo(2peak ) ) strongly predicts mortality in cardiac patients . We compared the effects of aerobic interval training ( AIT ) versus moderate continuous training ( MCT ) on Vo(2peak ) and quality of life after coronary artery bypass grafting ( CABG ) . METHODS Fifty-nine CABG patients were r and omized to either AIT at 90 % of maximum heart rate or MCT at 70 % of maximum heart rate , 5 d/wk , for 4 weeks at a rehabilitation center . Primary outcome was Vo(2peak ) , at baseline , after rehabilitation ( 4 weeks ) , and after 6 months of home-based exercise ( 6 months ) . RESULTS Vo(2peak ) increased between baseline and 4 weeks in AIT ( 27.1 + /- 4.5 vs 30.4 + /- 5.5 mL.kg(-1).min(-1 ) , P < .001 ) and MCT ( 26.2 + /- 5.2 vs 28.5 + /- 5.6 mL.kg(-1).min(-1 ) , P < .001 ; group difference , not significant ) . Aerobic interval training increased Vo(2peak ) between 4 weeks and 6 months ( 30.4 + /- 5.5 vs 32.2 + /- 7.0 mL.kg(-1).min(-1 ) , P < .001 ) , with no significant change in MCT ( 28.5 + /- 5.6 vs 29.5 + /- 5.7 mL.kg(-1).min(-1 ) ) . Quality of life improved in both groups from baseline to 4 weeks , remaining improved at 6 months . There were no changes in echocardiographic systolic and diastolic left ventricular function . Adiponectin increased between 4 weeks and 6 months in both groups ( group differences , not significant ) . CONCLUSIONS Four weeks of intense training increased Vo(2peak ) significantly after both AIT and MCT . Six months later , the AIT group had a significantly higher Vo(2peak ) than MCT . The results indicate that AIT and MCT increase Vo(2peak ) similarly in the short term , but with better long-term effect of AIT after CABG We found that interval training provides an effective means to improve the cardiovascular fitness and health status of highly functional patients with coronary artery disease . We also revealed that interval training improves anaerobic tolerance to a greater extent than the traditional exercise training model without increasing the risk to the patient . This research supports the implementation of interval training for highly functional patients with coronary artery disease Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective Peak oxygen uptake ( VO2peak ) is a strong predictor of survival in cardiac patients . The aims of this study were to compare the effects of high interval training ( HIT ) to moderate continuous training ( MCT ) on VO2peak and to identify the safety of HIT in acute myocardial infa rct ion patients with drug-eluting stent . Design Twenty-eight acute myocardial infa rct ion patients with drug-eluting stent were r and omized to either HIT at 85%–95 % of heart rate reserve or MCT at 70%–85 % of heart rate reserve , 3 days a week for 6 wks at a cardiac rehabilitation clinic . Primary outcome was VO2peak at baseline and after cardiac rehabilitation . Results Both HIT and MCT groups showed significant increases in VO2peak and heart rate recovery after 6 wks of training . The 22.16 % improvement in VO2peak in the HIT group was significantly greater than the 8.48 % improvement in the MCT group ( P = 0.021 ) . There were no cardiovascular events related to both HIT and MCT . Conclusions HIT is more effective than MCT for improving VO2peak in acute myocardial infa rct ion patients with drug-eluting stent . These findings may have important implication s for more effective exercise training in cardiac rehabilitation program OBJECTIVE : The purpose of this study was to evaluate the following : 1 ) the effects of continuous exercise training and interval exercise training on the end-tidal carbon dioxide pressure ( PETCO2 ) response during a grade d exercise test in patients with coronary artery disease ; and 2 ) the effects of exercise training modalities on the association between PETCO2 at the ventilatory anaerobic threshold ( VAT ) and indicators of ventilatory efficiency and cardiorespiratory fitness in patients with coronary artery disease . METHODS : Thirty-seven patients ( 59.7±1.7 years ) with coronary artery disease were r and omly divided into two groups : continuous exercise training ( n = 20 ) and interval exercise training ( n = 17 ) . All patients performed a grade d exercise test with respiratory gas analysis before and after three months of the exercise training program to determine the VAT , respiratory compensation point ( RCP ) and peak oxygen consumption . RESULTS : After the interventions , both groups exhibited increased cardiorespiratory fitness . Indeed , the continuous exercise and interval exercise training groups demonstrated increases in both ventilatory efficiency and PETCO2 values at VAT , RCP , and peak of exercise . Significant associations were observed in both groups : 1 ) continuous exercise training ( PETCO2VAT and cardiorespiratory fitness r = 0.49 ; PETCO2VAT and ventilatory efficiency r = -0.80 ) and 2 ) interval exercise training ( PETCO2VAT and cardiorespiratory fitness r = 0.39 ; PETCO2VAT and ventilatory efficiency r = -0.45 ) . CONCLUSIONS : Both exercise training modalities showed similar increases in PETCO2 levels during a grade d exercise test in patients with coronary artery disease , which may be associated with an improvement in ventilatory efficiency and cardiorespiratory fitness Aims . High-intensity interval training ( HIIT ) leads to improvements in various markers of cardiometabolic health but adherence to HIIT following a supervised laboratory intervention has yet to be tested . We compared self-report and objective measures of physical activity after one month of independent exercise in individuals with prediabetes who were r and omized to HIIT ( n = 15 ) or traditional moderate-intensity continuous training ( MICT , n = 17 ) . Method . After completing 10 sessions of supervised training participants were asked to perform HIIT or MICT three times per week for four weeks . Results . Individuals in HIIT ( 89 ± 11 % ) adhered to their prescribed protocol to a greater extent than individuals in MICT ( 71 ± 31 % ) as determined by training logs completed over one-month follow-up ( P = 0.05 , Cohen 's d = 0.75 ) . Minutes spent in vigorous physical activity per week measured by accelerometer were higher in HIIT ( 24 ± 18 ) as compared to MICT ( 11 ± 10 ) at one-month follow-up ( P = 0.049 , Cohen 's d = 0.92 ) . Cardiorespiratory fitness and systolic blood pressure assessed at one-month follow-up were equally improved ( P 's < 0.05 ) . Conclusions . This study provides preliminary evidence that individuals with prediabetes can adhere to HIIT over the short-term and do so at a level that is greater than MICT Background . We tested the hypothesis that high intensity interval training ( HIIT ) would be more effective than moderate intensity continuous training ( MIT ) to improve newly emerged markers of cardiorespiratory fitness in coronary heart disease ( CHD ) patients , as the relationship between ventilation and carbon dioxide production ( VE/VCO2 slope ) , oxygen uptake efficiency slope ( OUES ) , and oxygen pulse ( O2P ) . Methods . Seventy-one patients with optimized treatment were r and omly assigned into HIIT ( n = 23 , age = 56 ± 12 years ) , MIT ( n = 24 , age = 62 ± 12 years ) , or nonexercise control group ( CG ) ( n = 24 , age = 64 ± 12 years ) . MIT performed 30 min of continuous aerobic exercise at 70–75 % of maximal heart rate ( HRmax ) , and HIIT performed 30 min sessions split in 2 min alternate bouts at 60%/90 % HRmax ( 3 times/week for 16 weeks ) . Results . No differences among groups ( before versus after ) were found for VE/VCO2 slope or OUES ( P > 0.05 ) . After training the O2P slope increased in HIIT ( 22 % , P < 0.05 ) but not in MIT ( 2 % , P > 0.05 ) , while decreased in CG ( −20 % , P < 0.05 ) becoming lower versus HIIT ( P = 0.03 ) . Conclusion . HIIT was more effective than MIT for improving O2P slope in CHD patients , while VE/VCO2 slope and OUES were similarly improved by aerobic training regimens versus controls Exercise adherence is affected by factors including perceptions of enjoyment , time availability , and intrinsic motivation . Approximately 50 % of individuals withdraw from an exercise program within the first 6 mo of initiation , citing lack of time as a main influence . Time efficient exercise such as high intensity interval training ( HIIT ) may provide an alternative to moderate intensity continuous exercise ( MICT ) to elicit substantial health benefits . This study examined differences in enjoyment , affect , and perceived exertion between MICT and HIIT . Twelve recreationally active men and women ( age = 29.5 ± 10.7 yr , VO2max = 41.4 ± 4.1 mL/kg/min , BMI = 23.1 ± 2.1 kg/m2 ) initially performed a VO2max test on a cycle ergometer to determine appropriate workloads for subsequent exercise bouts . Each subject returned for two additional exercise trials , performing either HIIT ( eight 1 min bouts of cycling at 85 % maximal workload ( Wmax ) with 1 min of active recovery between bouts ) or MICT ( 20 min of cycling at 45 % Wmax ) in r and omized order . During exercise , rating of perceived exertion ( RPE ) , affect , and blood lactate concentration ( BLa ) were measured . Additionally , the Physical Activity Enjoyment Scale ( PACES ) was completed after exercise . Results showed higher enjoyment ( p = 0.013 ) in response to HIIT ( 103.8 ± 9.4 ) versus MICT ( 84.2 ± 19.1 ) . Eleven of 12 participants ( 92 % ) preferred HIIT to MICT . However , affect was lower ( p<0.05 ) and HR , RPE , and BLa were higher ( p<0.05 ) in HIIT versus MICT . Although HIIT is more physically dem and ing than MICT , individuals report greater enjoyment due to its time efficiency and constantly changing stimulus . Trial Registration : NCT:02981667 Objective : Exercise capacity strongly predicts survival and aerobic interval training ( AIT ) increases peak oxygen uptake effectively in cardiac patients . Usual care in Norway provides exercise training at the hospitals following myocardial infa rct ion ( MI ) , but the effect and actual intensity of these rehabilitation programmes are unknown . Design : R and omized controlled trial . Setting : Hospital cardiac rehabilitation . Subjects : One hundred and seven patients , recruited two to 12 weeks after MI , were r and omized to usual care rehabilitation or treadmill AIT . Interventions : Usual care aerobic group exercise training or treadmill AIT as 4 × 4 minutes intervals at 85–95 % of peak heart rate . Twice weekly exercise training for 12 weeks . Main measures : The primary outcome measure was peak oxygen uptake . Secondary outcome measures were endothelial function , blood markers of cardiovascular disease , quality of life , resting heart rate , and heart rate recovery . Results : Eighty-nine patients ( 74 men , 15 women , 57.4 ± 9.5 years ) completed the programme . Peak oxygen uptake increased more ( P = 0.002 ) after AIT ( from 31.6 ± 5.8 to 36.2 ± 8.6 mL·kg−1·min−1 , P < 0.001 ) than after usual care rehabilitation ( from 32.2 ± 6.7 to 34.7 ± 7.9 mL·kg−1·min−1 , P < 0.001 ) . The AIT group exercised with significantly higher intensity in the intervals compared to the highest intensity in the usual care group ( 87.3 ± 3.9 % versus 78.7 ± 7.2 % of peak heart rate , respectively , P < 0.001 ) . Both programmes increased endothelial function , serum adiponectin , and quality of life , and reduced serum ferritin and resting heart rate . High-density lipoprotein cholesterol increased only after AIT . Conclusions : AIT increased peak oxygen uptake more than the usual care rehabilitation provided to MI patients by Norwegian hospitals Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists PURPOSE Isocaloric interval exercise training programs have been shown to elicit improvements in numerous physiological indices in patients with CAD . Low-volume high-intensity interval exercise training ( HIT ) is effective in healthy population s ; however , its effectiveness in cardiac rehabilitation has not been established . This study compared the effects of 12-wk of HIT and higher-volume moderate-intensity endurance exercise ( END ) on brachial artery flow-mediated dilation ( FMD ) and cardiorespiratory fitness ( VO2 peak ) in patients with CAD . METHODS Twenty-two patients with documented CAD were r and omized into HIT ( n = 11 ) or END ( n = 11 ) based on pretraining FMD . Both groups attended two supervised sessions per week for 12 wk . END performed 30 - 50 min of continuous cycling at 58 % peak power output ( PPO ) , whereas HIT performed ten 1-min intervals at 89 % PPO separated by 1-min intervals at 10 % PPO per session . RESULTS Relative FMD was increased posttraining ( END , 4.4 % ± 2.6 % vs 5.9 % ± 3.6 % ; HIT , 4.6 % ± 3.6 % vs 6.1 % ± 3.4 % , P ≤ 0.001 pre- vs posttraining ) with no differences between groups . A training effect was also observed for relative VO2 peak ( END , 18.7 ± 5.7 vs 22.3 ± 6.1 mL · kg(-1 ) · min(-1 ) ; HIT , 19.8 ± 3.7 vs 24.5 ± 4.5 mL · kg(-1 ) · min(-1 ) , P < 0.001 for pre- vs posttraining ) , with no group differences . CONCLUSIONS Low-volume HIT provides an alternative to the current , more time-intensive prescription for cardiac rehabilitation . HIT elicited similar improvements in fitness and FMD as END , despite differences in exercise duration and intensity Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions Background — A well-developed coronary collateral circulation provides a potential source of blood supply in coronary artery disease . However , the prognostic importance and functional relevance of coronary collaterals is controversial with the association between exercise training and collateral growth still unclear . Methods and Results — This prospect i ve , open-label study r and omly assigned 60 patients with significant coronary artery disease ( fractional flow reserve ⩽0.75 ) to high-intensity exercise ( group A , 20 patients ) or moderate-intensity exercise ( group B , 20 patients ) for 4 weeks or to a control group ( group C , 20 patients ) . The primary end point was the change of the coronary collateral flow index ( CFI ) after 4 weeks . Analysis was based on the intention to treat . After 4 weeks , baseline CFI increased significantly by 39.4 % in group A ( from 0.142±0.07 at beginning to 0.198±0.09 at 4 weeks ) in comparison with 41.3 % in group B ( from 0.143±0.06 to 0.202±0.09 ) , whereas CFI in the control group remained unchanged ( 0.7 % , from 0.149±0.09 to 0.150±0.08 ) . High-intensity exercise did not lead to a greater CFI than moderate-intensity training . After 4 weeks , exercise capacity , VO2 peak and ischemic threshold increased significantly in group A and group B in comparison with group C with no difference between group A and group B. Conclusions — A significant improvement in CFI was demonstrated in response to moderate- and high-intensity exercise performed for 10 hours per week . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01209637 OBJECTIVES To determine the effects of resistance training combined with either moderate-intensity endurance or low-volume high-intensity interval training on cardiovascular risk profiles in patients with coronary artery disease . DESIGN Factorial repeated- measures study design . METHODS Nineteen patients were r and omized into moderate-intensity endurance ( n = 10 ) or high-intensity interval ( n = 9 ) groups , and attended 2 supervised exercise sessions a week for 6-months . The first 3-months involved exclusive moderate-intensity endurance or high-intensity interval exercise , after which progressive resistance training was added to both groups for the remaining 3-months . Fitness ( VO(2)peak ) , blood pressure and heart rate , lipid profiles and health related quality of life assessment s were performed at pretraining , 3 and 6-months training . RESULTS VO(2)peak increased from pretraining to 3-months in both groups ( moderate-intensity endurance : 19.8 ± 7.3 vs. 23.2 ± 7.4 ml kg(-1)min(-1 ) ; high-intensity interval : 21.1 ± 3.3 vs. 26.4 ± 5.2 ml kg(-1)min(-1 ) , p<0.001 ) with no further increase at 6-months . Self-evaluated health and high-density lipoprotein were increased following 6-months of moderate-intensity endurance exercise , while all remaining indices were unchanged . Low-volume high-intensity interval exercise did not elicit improvements in lipids or health related quality of life . Blood pressures and heart rates were unchanged with training in both groups . CONCLUSIONS Findings from our pilot study suggest improvements in fitness occur within the first few months of training in patients with coronary artery disease , after which the addition of resistance training to moderate-intensity endurance and high-intensity interval exercise elicited no further improvements . Given the importance of resistance training in cardiac rehabilitation , additional research is required to determine its effectiveness when combined with high-intensity interval exercise PURPOSE To determine whether exercise at low intensity ( LO ; 50 % of peak VO2 ) or high intensity ( HI ; 85 % of peak VO2 ) results in improvement of the ventilatory threshold ( VT ) , 186 men with coronary artery disease ( CAD ) were enrolled in an exercise study for 1 year . METHODS A symptom-limited exercise test was performed at baseline and the heart rate corresponding to 50 % and 85 % of peak VO2 was determined . Subjects were r and omized to LO or HI intensity exercise . Exercise sessions included 45 minutes of walking/jogging and /or stationary cycling at the appropriate target heart rate and were conducted 3 days per week . The exercise test was repeated at 3 and 6 months . Target heart rates were revised to adjust for training . RESULTS Both LO and HI result ed in improved VO2 at VT and peak . However , HI result ed in greater improvement than LO . CONCLUSION Among this population , both HI and LO improve the VO2 at VT and peak , but the improvement is greater with HI . The VT can be a useful adjunct to heart rate and peak oxygen uptake when prescribing exercise Background Increased aerobic exercise capacity appears to reduce both all-cause mortality and cardiovascular disease mortality . Physical exercise to improve peak oxygen uptake ( VO2peak ) is thus strongly recommended , however evidence regarding the most efficient training intensity for patients with coronary artery disease ( CAD ) is still lacking . The purpose of this r and omized study was therefore to assess the effects of high intensity aerobic interval exercise compared to moderate intensity exercise , representing the same total training load , for increasing VO2peak in stable CAD- patients . Methods Twenty-one stable CAD- patients were r and omized to supervised treadmill walking at either high intensity ( 80–90 % of VO2peak ) or moderate intensity ( 50–60 % of VO2peak ) three times a week for 10 weeks . Results After training VO2peak increased by 17.9 % ( P = 0.012 ) in the high intensity group and 7.9 % ( P = 0.038 ) in the moderate intensity group . The training-induced adaptation was significantly higher in the high intensity group ( P = 0.011 ) . Conclusions High intensity aerobic interval exercise is superior to moderate exercise for increasing VO2peak in stable CAD- patients . As VO2peak seems to reflect a continuum between health and cardiovascular disease and death , the present data may be useful in design ing effective training programmes for improved health in the future BACKGROUND Studies relating physical exercises and health have contributed to eluci date the influence of sedentary habits on the incidence of cardiovascular diseases . OBJECTIVE To compare the effect of different intensities of aerobic exercises on patients ' functional capacity ( VO₂(peak ) ) and quality of life after acute myocardial infa rct ion . METHODS Eighty-seven men ( 57.7 ± 6.1 years old ) were enrolled in this prospect i ve study and assigned to one of three groups : a ) high-intensity physical training ( n=29 ) at 85 % maximum heart rate for 12 weeks ; b ) moderate-intensity training ( n=29 ) at 75 % maximum heart rate for 12 weeks ; and c ) control group ( n=29 ) , who were followed . The training groups did aerobic exercises five times a week in 45-minute sessions , besides muscular strengthening and stretching exercises . Maximum VO₂ was measured through a cardiopulmonary test , and quality of life was assessed through the MacNew Question naire . RESULTS Two-way ANOVA revealed a significant increase in VO₂(peak ) ( p<0.05 ) in the high-intensity training group ( from 29.9 ± 2.2 ml/kg.min to 41.6± 3.9 ml/kg.min ) compared with the moderate-intensity training group ( from 32.0 ± 5.3 ml/kg.min to 37.1 ± 3.9 ml/kg.min ) . Additionally , both training groups showed a significant increase in this parameter compared with the control group ( from 31.6 ± 3.9 ml/kg.min to 29.2 ±4.1 ml/kg.min ) . Quality of life improved significantly ( p<0.05 ) in the high-intensity training group ( from 5.66 to 6.80 ) and in the moderate-intensity training group ( from 5.38 to 6.72 ) , but not in the control group ( from 5.30 to 5.15 ) . CONCLUSION Exercises of greater intensity result ed in an increase in functional capacity and quality of life in patients after myocardial infa rct ion PURPOSE : We tested the hypothesis that higher-intensity interval training ( HIIT ) could be deployed into a st and ard cardiac rehabilitation ( CR ) setting and would result in a greater increase in cardiorespiratory fitness ( ie , peak oxygen uptake , ) versus moderate-intensity continuous training ( MCT ) . METHODS : Thirty-nine patients participating in a st and ard phase 2 CR program were r and omized to HIIT or MCT ; 15 patients and 13 patients in the HIIT and MCT groups , respectively , completed CR and baseline and followup cardiopulmonary exercise testing . RESULTS : No patients in either study group experienced an event that required hospitalization during or within 3 hours after exercise . The changes in resting heart rate and blood pressure at followup testing were similar for both HIIT and MCT . at ventilatory-derived anaerobic threshold increased more ( P < .05 ) with HIIT ( 3.0 ± 2.8 mL·kg·−1min−1 ) versus MCT ( 0.7 ± 2.2 mL·kg·−1min−1 ) . During followup testing , submaximal heart rate at the end of stage 2 of the exercise test was significantly lower within both the HIIT and MCT groups , with no difference noted between groups . Peak V˙o2 improved more after CR in patients in HIIT versus MCT ( 3.6 ± 3.1 mL·kg.−1·min−1 vs 1.7 ± 1.7 mL·kg.−1·min−1 ; P < .05 ) . CONCLUSIONS : Among patients with stable coronary heart disease on evidence -based therapy , HIIT was successfully integrated into a st and ard CR setting and , when compared to MCT , result ed in greater improvement in peak exercise capacity and submaximal endurance |
1,654 | 24,756,350 | Based on the best available evidence , it appears that adding gene therapy with HSV-tk has some effect in treating HGG patients , especially with respect to MST .
However , neither the pooled analysis of OS , nor the combined analysis of tumor progress indicates any significant advantage to adding gene therapy compared with st and ard treatment alone . | The aim of this study was to assess the effectiveness of adding viral vector-mediated gene therapy with herpes simplex virus thymidine kinase ( HSV-tk ) to st and ard treatment , in comparison with st and ard treatment alone to treat patients with high- grade gliomas ( HGGs ) . | Malignant glioma is a devastating brain tumor with no effective treatment . This r and omised , controlled study involved 36 patients with operable primary or recurrent malignant glioma . Seventeen patients were r and omized to receive AdvHSV-tk gene therapy ( 3 x 10(10 ) pfu ) by local injection into the wound bed after tumor resection , followed by intravenous ganciclovir ( GCV ) , 5 mg/kg twice daily for 14 days . The control group of 19 patients received st and ard care consisting of radical excision followed by radiotherapy in those patients with primary tumors . The primary end-point was survival as defined by death or surgery for recurrence . Secondary end-points were all-cause mortality and tumour progression as determined by MRI . Overall safety and quality of life were also assessed . Findings were also compared with historical controls ( n = 36 ) from the same unit over 2 years preceding the study . AdvHSV-tk treatment produced a clinical ly and statistically significant increase in mean survival from 39.0 + /- 19.7 ( SD ) to 70.6 + /- 52.9 weeks ( P = 0.0095 , log-rank regression vs. r and omized controls ) . The median survival time increased from 37.7 to 62.4 weeks . Six patients had increased anti-adenovirus antibody titers , without adverse effects . The treatment was well tolerated . It is concluded that AdvHSV-tk gene therapy with GCV is a potential new treatment for operable primary or recurrent high- grade glioma The management of patients with glioblastoma remains challenging with an average survival of 32–56 weeks . We report on a clinical trial of patients with recurrent glioblastoma treated with adenovirus/herpex simplex-thymidine kinase/ganciclovir (ADV/HSV-tk/GC).Entry criteria for this study included : recurrent malignant glioma after surgical resection and conventional radiation therapy . At the time of recurrence , computerized volumetric resection of the tumor was performed and the ADV/HSV-tk complex was injected in the tumor bed . GC was administered 24 h after surgery ( 10 mg/kg/day ) for 7 days . Patients were divided into 3 ADV/HSV-tk dose-escalating cohorts . Adenoviral vector shedding , and local or systemic toxicity did not occur in this study . Magnetic resonance imaging showed lack of increased brain edema in the treated patients . Histological examination of the 5 patients that had repeated surgery after gene therapy treatment showed lack of tissue toxicity . Additionally , PCR for HSV-tk was negative in the brain 3 months after injection . The patients ' Karnofsky score was maintained ≥70 in 8/10 patients ( 80 % ) and 5/9 patients ( 55 % ) 3 and 6 months respectively , after gene therapy . Ten of 11 patients survived ≥52 weeks from diagnosis with an average survival of 112.3 weeks . One patient is still alive 248 weeks from diagnosis . These data show that the ADV/HSV-tk/GC complex at the dose used in this study is safe . Additional dose escalation is currently in progress Between December 1996 and September 1998 , 13 patients with advanced recurrent malignant brain tumors ( 9 with glioblastoma multiforme , 1 with gliosarcoma , and 3 with anaplastic astrocytoma ) were treated with a single intratumoral injection of 2 x 10(9 ) , 2 x 10(10 ) , 2 x 10(11 ) , or 2 x 10(12 ) vector particles ( VP ) of a replication-defective adenoviral vector bearing the herpes simplex virus thymidine kinase gene driven by the Rous sarcoma virus promoter ( Adv . RSVtk ) , followed by ganciclovir ( GCV ) treatment . The VP to infectious unit ratio was 20:1 . Our primary objective was to determine the safety of this treatment . Injection of Adv . RSVtk in doses < = = 2 x 10(11 ) VP , followed by GCV , was safely tolerated . Patients treated with the highest dose , 2 x 10(12 ) VP , exhibited central nervous system toxicity with confusion , hyponatremia , and seizures . One patient is living and stable 29.2 months after treatment . Two patients survived > 25 months before succumbing to tumor progression . Ten patients died within 10 months of treatment , 9 from tumor progression and 1 with sepsis and endocarditis . Neuropathologic examination of postmortem tissue demonstrated cavitation at the injection site , intratumoral foci of coagulative necrosis , and variable infiltration of the residual tumor with macrophages and lymphocytes To determine the safety and evaluate the efficacy of repeated administration of virus-producing cells ( GLI 328 ) containing the herpes simplex virus thymidine-kinase gene followed by ganciclovir treatment in adults with recurrent glioblastoma multiforme , we conducted a phase I/II multi-institutional trial . Eligible patients underwent surgical resection of tumor , followed by injections of vector producing cells ( VPC ) into the brain adjacent to the cavity . An Ommaya reservoir placed after surgery was used to inject a further dose of VPC seven days after surgery , followed seven days later by ganciclovir . Further gene therapy was given at 28-day intervals for up to a total of five cycles . Toxicity and anti-tumor effect were assessed . Of 30 patients who enrolled in the study , 16 experienced serious adverse events possibly related to the experimental therapy . Laboratory testing , including polymerase chain reaction analysis to detect replication-competent retrovirus in peripheral blood lymphocytes and tissues , as well as co-cultivation bioassays , were negative . Before receiving ganciclovir , 37 % of the patients showed evidence of transduced peripheral blood leukocytes , but only 12 % showed a persistence of transduced cells at the end of the first cycle of ganciclovir . Median survival was 8.4 months . Twenty percent of the patients ( n = 6 ) survived more than 12 months from the date of study entry . This treatment modality is feasible and appears to have some evidence of efficacy . Toxicity may be related in part to the method of gene delivery PURPOSE Despite aggressive therapies , median survival for malignant gliomas is less than 15 months . Patients with unmethylated O(6)-methylguanine-DNA methyltransferase ( MGMT ) fare worse , presumably because of temozolomide resistance . AdV-tk , an adenoviral vector containing the herpes simplex virus thymidine kinase gene , plus prodrug synergizes with surgery and chemoradiotherapy , kills tumor cells , has not shown MGMT dependency , and elicits an antitumor vaccine effect . PATIENTS AND METHODS Patients with newly diagnosed malignant glioma received AdV-tk at 3 × 10(10 ) , 1 × 10(11 ) , or 3 × 10(11 ) vector particles ( vp ) via tumor bed injection at time of surgery followed by 14 days of valacyclovir . Radiation was initiated within 9 days after AdV-tk injection to overlap with AdV-tk activity . Temozolomide was administered after completing valacyclovir treatment . RESULTS Accrual began December 2005 and was completed in 13 months . Thirteen patients were enrolled and 12 completed therapy , three at dose levels 1 and 2 and six at dose level 3 . There were no dose-limiting or significant added toxicities . One patient withdrew before completing prodrug because of an unrelated surgical complication . Survival at 2 years was 33 % and at 3 years was 25 % . Patient-reported quality of life assessed with the Functional Assessment of Cancer Therapy-Brain ( FACT-Br ) was stable or improved after treatment . A significant CD3(+ ) T-cell infiltrate was found in four of four tumors analyzed after treatment . Three patients with MGMT unmethylated glioblastoma multiforme survived 6.5 , 8.7 , and 46.4 months . CONCLUSION AdV-tk plus valacyclovir can be safely delivered with surgery and accelerated radiation in newly diagnosed malignant gliomas . Temozolomide did not prevent immune responses . Although not powered for efficacy , the survival and MGMT independence trends are encouraging . A phase II trial is ongoing Abstract Object : In mouse models of prostate and breast cancer therapeutic effects are enhanced when adenoviral HSV TK gene therapy is combined with ionizing radiation . In the present study , we adopted this approach for the treatment of human glioblastoma xenografts in an athymic mouse model and assessed treatment results as well as toxic side effects . Methods : About 72 nude mice received intracerebral inoculations of 2 × 105 U87ΔEGFR cells . On day 7 after tumor implantation the study population was r and omized into six treatment arms : ( 1 ) intratumoral buffer inoculation on day 7 , ( 2 ) intratumoral adenoviral vector injection ( 2 × 109 vp ) on day 7 , ( 3 ) single dose radiation ( 2.1 Gy ) on day 9 , ( 4 ) adenoviral injection + radiation , ( 5 ) adenoviral injection + ganciclovir ( GCV ) ( 20 ug/g twice daily from day 8 to 17 ) , ( 6 ) adenoviral injection + GCV + radiation . On day 21 half of the animals were sacrificed for histological evaluation of the brain tumors , the other half was assessed for survival . Results : This study showed significantly prolonged median survival time of 5 days for the GCV treated groups . The addition of radiation decreased the frequency of neurological symptoms and delayed the onset of deficits without altering the expression of thymidine kinase in the tumor cells . Conclusions : We conclude that adenoviral HSV TK gene therapy in combination with adjuvant radiotherapy does not generate increased toxic side effects in glioblastoma treatment . The prolonged survival time of animals receiving gene therapy and the reduced occurrence of neurological symptoms in irradiated mice constitute promising features of the combined treatment Herpes simplex virus thymidine kinase ( HSV tk ) gene therapy combined with ganciclovir ( GCV ) medication is a potential new method for the treatment of malignant glioma . We have used both retrovirus-packaging cells ( PA317/tk ) and adenoviruses ( Adv/tk ) for gene therapy for malignant glioma . Retrovirus-packaging cells were used for eight tumors in seven patients and adenoviruses were used for seven tumors in seven patients . As a control group , seven tumors in seven patients were transduced with lacZ marker gene 4 - 5 days before tumor resection . Safety and efficacy of the gene therapy were studied with clinical evaluation , blood and urine sample s , MRI follow-up , and survival of the patients . Four patients with adenovirus injections had a significant increase in anti-adenovirus antibodies and two of them had a short-term fever reaction . Frequency of epileptic seizures increased in two patients . No other adverse events possibly related to gene therapy were detected . In the retrovirus group , all treated gliomas showed progression by MRI at the 3-month time point , whereas three of the seven patients treated with Adv/tk remained stable ( p < 0.05 ) . Mean survival times for retrovirus , adenovirus , and control groups were 7.4 , 15.0 , and 8 . 3 months , respectively . The difference in the survival times between the adenovirus and retrovirus groups was significant ( p < 0.012 ) . It is concluded that HSV tk gene therapy is safe and well tolerated . On the basis of these results further trials are justified , especially with adenovirus vectors Intratumoral implantation of murine cells modified to produce retroviral vectors containing the herpes simplex virus-thymidine kinase ( HSV-TK ) gene induces regression of experimental brain tumors in rodents after ganciclovir ( GCV ) administration . We evaluated this approach in 15 patients with progressive growth of recurrent malignant brain tumors . Antitumor activity was detected in five of the smaller tumors ( 1.4 ± 0.5 ml ) . In situ hybridization for HSV-TK demonstrated survival of vector-producing cells ( VPCs ) at 7 days but indicated limited gene transfer to tumors , suggesting that indirect , “ byst and er , ” mechanisms provide local antitumor activity in human tumors . However , the response of only very small tumors in which a high density of vector-producing cells had been placed suggests that techniques to improve delivery and distribution of the therapeutic gene will need to be developed if clinical utility is to be achieved with this approach Previous uncontrolled clinical trials have shown the in vivo retrovirus (RV)-mediated transduction of glioblastoma cells with the herpes simplex virus thymidine kinase ( HSV-tk ) gene and subsequent systemic treatment with ganciclovir to be feasible and well tolerated . However , because of continued tumor progression in most patients , the antitumor effect could not be determined using historical controls . Here , we describe a phase III , multicenter , r and omized , open-label , parallel-group , controlled trial of the technique in the treatment of 248 patients with newly diagnosed , previously untreated glioblastoma multiforme ( GBM ) . Patients received , in equal numbers , either st and ard therapy ( surgical resection and radiotherapy ) or st and ard therapy plus adjuvant gene therapy during surgery . Progression-free median survival in the gene therapy group was 180 days compared with 183 days in control subjects . Median survival was 365 versus 354 days , and 12-month survival rates were 50 versus 55 % in the gene therapy and control groups , respectively . These differences were not significant . Therefore , the adjuvant treatment improved neither time to tumor progression nor overall survival time , although the feasibility and good biosafety profile of this gene therapy strategy were further supported . The failure of this specific protocol may be due mainly to the presumably poor rate of delivery of the HSV-tk gene to tumor cells . In addition , the current mode of manual injection of vector-producing cells with a nonmigratory fibroblast phenotype limits the distribution of these cells and the released replication-deficient RV vectors to the immediate vicinity of the needle track . Further evaluation of the RV-mediated gene therapy strategy must incorporate refinements such as improved delivery of vectors and transgenes to the tumor cells , noninvasive in vivo assessment of transduction rates , and improved delivery of the prodrug across the blood-brain and blood-tumor barrier to the transduced tumor cells BACKGROUND In 2004 , a r and omised phase III trial by the European Organisation for Research and Treatment of Cancer ( EORTC ) and National Cancer Institute of Canada Clinical Trials Group ( NCIC ) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy . We report the final results with a median follow-up of more than 5 years . METHODS Adult patients with newly diagnosed glioblastoma were r and omly assigned to receive either st and ard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide . The methylation status of the methyl-guanine methyl transferase gene , MGMT , was determined retrospectively from the tumour tissue of 206 patients . The primary endpoint was overall survival . Analyses were by intention to treat . This trial is registered with Clinical trials.gov , number NCT00006353 . FINDINGS Between Aug 17 , 2000 , and March 22 , 2002 , 573 patients were assigned to treatment . 278 ( 97 % ) of 286 patients in the radiotherapy alone group and 254 ( 89 % ) of 287 in the combined-treatment group died during 5 years of follow-up . Overall survival was 27.2 % ( 95 % CI 22.2 - 32.5 ) at 2 years , 16.0 % ( 12.0 - 20.6 ) at 3 years , 12.1 % ( 8.5 - 16.4 ) at 4 years , and 9.8 % ( 6.4 - 14.0 ) at 5 years with temozolomide , versus 10.9 % ( 7.6 - 14.8 ) , 4.4 % ( 2.4 - 7.2 ) , 3.0 % ( 1.4 - 5.7 ) , and 1.9 % ( 0.6 - 4.4 ) with radiotherapy alone ( hazard ratio 0.6 , 95 % CI 0.5 - 0.7 ; p<0.0001 ) . A benefit of combined therapy was recorded in all clinical prognostic subgroups , including patients aged 60 - 70 years . Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy . INTERPRETATION Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up . A few patients in favourable prognostic categories survive longer than 5 years . MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide . FUNDING EORTC , NCIC , Nélia and Amadeo Barletta Foundation , Schering-Plough BACKGROUND Besides the use of temozolomide and radiotherapy for patients with favourable methylation status , little progress has been made in the treatment of adult glioblastoma . Local control of the disease by complete removal increases time to progression and survival . We assessed the efficacy and safety of a locally applied adenovirus-mediated gene therapy with a prodrug converting enzyme ( herpes-simplex-virus thymidine kinase ; sitimagene ceradenovec ) followed by intravenous ganciclovir in patients with newly diagnosed resectable glioblastoma . METHODS For this international , open-label , r and omised , parallel group multicentre phase 3 clinical trial , we recruited patients from 38 sites in Europe . Patients were eligible if they were aged 18 - 70 years , had newly diagnosed supratentorial glioblastoma multiforme amenable to complete resection , and had a Karnofsky score of 70 or more at screening . We used a computer-generated r and omisation sequence to allocate patients in a one-to-one ratio ( with block sizes of four ) to receive either surgical resection of the tumour and intraoperative perilesional injection of sitimagene ceradenovec ( 1 × 10(12 ) viral particles ) followed by ganciclovir ( postoperatively , 5 mg/kg intravenously twice a day ) in addition to st and ard care or resection and st and ard care alone . Temozolomide , not being st and ard in all participating countries at the time of the study , was allowed at the discretion of the treating physician . The primary endpoint was a composite of time to death or re-intervention , adjusted for temozolamide use , assessed by intention-to-treat ( ITT ) analysis . This trial is registered with EudraCT , number 2004 - 000464 - 28 . FINDINGS Between Nov 3 , 2005 , and April 16 , 2007 , 250 patients were recruited and r and omly allocated : 124 to the experimental group and 126 to the st and ard care group , of whom 119 and 117 patients , respectively , were included in the ITT analyses . Median time to death or re-intervention was longer in the experimental group ( 308 days , 95 % CI 283 - 373 ) than in the control group ( 268 days , 210 - 313 ; hazard ratio [ HR ] 1·53 , 95 % CI 1·13 - 2·07 ; p=0·006 ) . In a subgroup of patients with non-methylated MGMT , the HR was 1·72 ( 95 % CI 1·15 - 2·56 ; p=0·008 ) . However , there was no difference between groups in terms of overall survival ( median 497 days , 95 % CI 369 - 574 for the experimental group vs 452 days , 95 % CI 437 - 558 for the control group ; HR 1·18 , 95 % CI 0·86 - 1·61 , p=0·31 ) . More patients in the experimental group had one or more treatment-related adverse events those in the control group ( 88 [ 71 % ] vs 51 [ 43 % ] ) . The most common grade 3 - 4 adverse events were hemiparesis ( eight in the experimental group vs three in the control group ) and aphasia ( six vs two ) . INTERPRETATION Our findings suggest that use of sitimagene ceradenovec and ganciclovir after resection can increase time to death or re-intervention in patients with newly diagnosed supratentorial glioblastoma multiforme , although the intervention did not improve overall survival . Locally delivered gene therapy for glioblastoma should be further developed , especially for patients who are unlikely to respond to st and ard chemotherapy . FUNDING Ark Therapeutics Despite extensive surgery for glioblastoma , residual tumor cells always lead to relapse . Gene therapy based on retrovirus-mediated gene transfer of herpes simplex virus type 1 thymidine kinase ( HSV-1 TK ) , which specifically sensitizes dividing cells to ganciclovir ( GCV ) toxicity , may help eradicate such cells . During glioblastoma surgery , HSV-1 TK retroviral vector-producing cells ( M11 ) were injected into the surgical cavity margins after tumor debulking . After a 7-day transduction period , GCV was administered for 14 days . Safety was assessed by clinical and laboratory evaluations , and efficacy was assessed by MRI-based relapse-free survival at month 4 and by overall survival . Twelve patients with recurrent glioblastoma were treated without serious adverse events related to M11 cell administration or GCV . Quality of life was not negatively influenced by this treatment . Overall median survival was 206 days , with 25 % of the patients surviving longer than 12 months . At 4 months after treatment , 4 of 12 patients had no recurrence ; their median overall survival was 528 days , compared with 194 days for patients with recurrence ( p=0.03 by the log rank test ) . One patient is still free of detectable recurrence , steroid free and independent , 2.8 years after treatment . Thus , brain injections of M11 retroviral vector-producing cells for glioblastoma HSV-1 TK gene therapy were well tolerated and associated with significant therapeutic responses . These results warrant further development of this therapeutic strategy in brain tumor , including recurrent glioblastoma This study has investigated the effects of herpes simplex thymidine kinase gene ( HSV-tk ) transfer followed by ganciclovir treatment as adjuvant gene therapy to surgical resection in patients with recurrent glioblastoma multiforme ( GBM ) . The study was open and single-arm , and aim ed at assessing the feasibility and safety of the technique and indications of antitumor activity . In 48 patients a suspension of retroviral vector-producing cells ( VPCs ) was administered by intracerebral injection immediately after tumor resection . Intravenous ganciclovir was infused daily 14 to 27 days after surgery . Patients were monitored for adverse events and for life by regular biosafety assaying . Tumor changes were monitored by magnetic resonance imaging ( MRI ) . Reflux during injection was a frequent occurrence but serious adverse events during the treatment period ( days 1 - 27 ) were few and of a nature not unexpected in this population . One patient experienced transient neurological disorders associated with postganciclovir MRI enhancement . There was no evidence of replication-competent retrovirus in peripheral blood leukocytes or in tissue sample s of reresection or autopsy . Vector DNA was shown in the leukocytes of some patients but not in autopsy gonadal sample s. The median survival time was 8.6 months , and the 12-month survival rate was 13 of 48 ( 27 % ) . On MRI studies , tumor recurrence was absent in seven patients for at least 6 months and for at least 12 months in two patients , one of whom remains recurrence free at more than 24 months . Treatment-characteristic images of injection tracks and intracavity hemoglobin were apparent . In conclusion , the gene therapy is feasible and appears to be satisfactorily safe as an adjuvant to the surgical resection of recurrent GBM , but any benefit appears to be marginal . Investigation of the precise effectiveness of this gene therapy requires prospect i ve , controlled studies Between November 1998 and December 2001 , we treated 14 patients with advanced recurrent high- grade gliomas with a total dose of 4.6 x 10(8 ) , 4.6 x 10(9 ) , 4.6 x 10(10 ) , or 4.6 x 10(11 ) viral particles ( VP ) of a replication-incompetent adenoviral vector harboring the herpes simplex virus thymidine kinase gene driven by the adenoviral major late promoter ( IG.Ad . MLPI.TK ) , followed by ganciclovir ( GCV ) treatment . The VP-to-infectious-unit ratio was 40 . The vector was administered by 50 intraoperative wound-bed injections of 0.2 ml each ( total volume 10 ml ) . The study 's primary objective was to determine the safety of this treatment and establish the maximum tolerated dose ( MTD ) . Injection of all doses of IG.Ad . MLPI.TK followed by GCV was safely tolerated and MTD was not reached . All patients had recurrence or progression of the tumor 1 - 24 months ( median 3.5 months ) after gene therapy . The overall median survival was 4 months . Four patients survived longer than 1 year following gene therapy . One patient is still alive , with histologically confirmed progression of the tumor , 29 months after treatment . Ten patients died within 8 months of treatment , all from progression of the tumor . In 5 patients residual and measurable tumor was visible on the direct ( < 48 h ) postoperative MRI . No objective radiological response was documented on subsequent MRI . None of the patients came to autopsy . In conclusion , the administration of 4.6 x 10(11 ) VP of IG.Ad . MLPI.TK by 50 injections into the wound bed following resection of recurrent malignant glioma , followed by GCV treatment , was well tolerated |
1,655 | 22,450,159 | These studies provided some evidence of positive therapeutic effect on quality of life , performance status , inflammatory markers , weight gain and survival , but there was insufficient evidence demonstrated for their widespread use in practice . | Background : Cancer cachexia is a devastating syndrome of advanced malignancy which negatively impacts on patients ’ morbidity , mortality and quality of life .
Chronic inflammation is a key characteristic of cancer cachexia .
Therefore , non-steroidal anti-inflammatory drugs ( NSAIDs ) may be able to break the cycle of cachexia .
Aim : To systematic ally review the literature on the use of NSAIDs for the treatment of cachexia in advanced cancer patients . | Background : Proinflammatory cytokines , especially tumour necrosis factor α ( TNF-α ) , play a prominent role in the pathogenesis of cancer cachexia . Thalidomide , which is an inhibitor of TNF-α synthesis , may represent a novel and rational approach to the treatment of cancer cachexia . Aims : To assess the safety and efficacy of thalidomide in attenuating weight loss in patients with cachexia secondary to advanced pancreatic cancer . Methods : Fifty patients with advanced pancreatic cancer who had lost at least 10 % of their body weight were r and omised to receive thalidomide 200 mg daily or placebo for 24 weeks in a single centre , double blind , r and omised controlled trial . The primary outcome was change in weight and nutritional status . Results : Thirty three patients ( 16 control , 17 thalidomide ) were evaluated at four weeks , and 20 patients ( eight control , 12 thalidomide ) at eight weeks . At four weeks , patients who received thalidomide had gained on average 0.37 kg in weight and 1.0 cm3 in arm muscle mass ( AMA ) compared with a loss of 2.21 kg ( absolute difference −2.59 kg ( 95 % confidence interval ( CI ) −4.3 to −0.8 ) ; p = 0.005 ) and 4.46 cm3 ( absolute difference −5.6 cm3 ( 95 % CI −8.9 to −2.2 ) ; p = 0.002 ) in the placebo group . At eight weeks , patients in the thalidomide group had lost 0.06 kg in weight and 0.5 cm3 in AMA compared with a loss of 3.62 kg ( absolute difference −3.57 kg ( 95 % CI −6.8 to −0.3 ) ; p = 0.034 ) and 8.4 cm3 ( absolute difference −7.9 cm3 ( 95 % CI −14.0 to −1.8 ) ; p = 0.014 ) in the placebo group . Improvement in physical functioning correlated positively with weight gain ( r = 0.56 , p = 0.001 ) . Conclusion : Thalidomide was well tolerated and effective at attenuating loss of weight and lean body mass in patients with cachexia due to advanced pancreatic cancer Background : The approval of a research ethics committee ( REC ) and obtaining informed consent from patients ( ICP ) could be considered the main issues in the ethics of research with human beings . The aim of this study was to assess both method ological quality and ethical quality , and also to assess the relationship between these two qualities in r and omised phase III cancer trials . Method : Method ological quality ( Jadad score ) and ethical quality ( Berdeu score ) were assessed for all r and omised controlled trials ( RCTs ) published in 10 international journals between 1999 and 2001 ( n = 231 ) . Results : The mean Jadad score was 9.86 ± 1.117 . The method ological quality was poor in 75 RCTs ( Jadad score < 9 ) . The mean Berdeu score was 0.42 ± 0.133 . The mean ethical quality score for poor method ological quality RCTs ( n = 75 ) was 0.39 ± 0.133 ; it was 0.43 ± 0.133 for good ( n = 156 ) method ological quality RCTs ( p = 0.07 ) . There was improvement in ethical quality according to the year of commencement of the trials ( p < 0.001 ) . There was no correlation between method ological quality and the number of participating patients ( R2 = 0.003 , p = 0.78 ) , between ethical quality and the number of participating patients ( R2 = 0.003 , p = 0.76 ) , or between ethical quality and method ological quality ( R2 = 0.012 , p = 0.1 ) . ICP and REC approval were not obtained for 21 and 77 trials respectively . Conclusion : The association between method ological quality and the reporting of ethical requirements probably reflects the respect shown for patients during the whole research process . These results suggest that closer attention to the conduct of clinical research , as well as the reporting of its ethical aspects , is needed The primary purpose of this study was to investigate the accuracy of the activPAL physical activity monitor in measuring step number and cadence in older adults . Two pedometers ( New-Lifestyles Digi-Walker SW-200 and New-Lifestyles NL2000 ) used in clinical practice to count steps were simultaneously evaluated . Observation was the criterion measure . Twenty-one participants ( 65 - 87 yr old ) recruited from community-based exercise classes walked on a treadmill at 5 speeds ( 0.67 , 0.90 , 1.12 , 1.33 , and 1.56 m/s ) and outdoors at 3 self-selected speeds ( slow , normal , and fast ) . The absolute percentage error of the activPAL was < 1 % for all treadmill and outdoor conditions for measuring steps and cadence . With the exception of the slowest treadmill speed , the NL-2000 error was < 2 % . The SW-200 was the least accurate device , particularly at slower walking speeds . The activPAL monitor accurately recorded step number and cadence . Combined with its ability to identify primary postures , the activPAL might be a useful and versatile device for measuring activity in older adults Summary The use of megestrol acetate in the treatment of weight loss in gastrointestinal cancer patients has been disappointing . The aim of the present study was to compare the combination of megestrol acetate and placebo with megestrol acetate and ibuprofen in the treatment of weight loss in such patients . At baseline , 4–6 weeks and 12 weeks , patients underwent measurements of anthropometry , concentrations of albumin and C-reactive protein and assessment of appetite , performance status and quality of life using EuroQol-EQ-5D and EORTC QLQ-C30 . Thirty-eight and 35 patients ( median weight loss 18 % ) were r and omized to megestrol acetate/placebo or megestrol acetate/ibuprofen , respectively , for 12 weeks . Forty-six ( 63 % ) of patients failed to complete the 12-week assessment . Of those evaluable at 12 weeks , there was a decrease in weight ( median 2.8 kg ) in the megestrol acetate/placebo group compared with an increase ( median 2.3 kg ) in the megestrol acetate/ibuprofen group ( P < 0.001 ) . There was also an improvement in the EuroQol-EQ-5D quality of life scores of the latter group ( P < 0.05 ) . The combination of megestrol acetate/ibuprofen appeared to reverse weight loss and appeared to improve quality of life in patients with advanced gastrointestinal cancer . Further trials of this novel regimen in weight-losing patients with hormone-insensitive cancers are warranted The aim of this study was to investigate the effect of the cyclo-oxygenase inhibitor ibuprofen on the acute-phase protein response and resting energy expenditure ( REE ) of weight-losing patients with pancreatic cancer . Patients with irresectable pancreatic cancer ( n = 16 ) were treated with either ibuprofen ( 1200 mg day-1 for 7 days ( n = 10 ) or placebo ( n = 6 ) . A group of 17 age-related non-cancer subjects were also studied . Indirect calorimetry , anthropometry , multifrequency bioelectrical impedence analysis and serum C-reactive protein ( CRP ) estimation were performed immediately before and after treatment . Before treatment , total REE was significantly elevated in the pancreatic cancer patients compared with healthy controls ( 1499 + /- 71 vs 1377 + /- 58 kcal ) ( P < 0.02 ) . Following treatment the mean REE of the ibuprofen group fell significantly ( 1386 + /- 89 kcal ) compared with pretreatment values ( 1468 + /- 99 kcal ) ( P < 0.02 ) , whereas no change was observed in the placebo group . Serum CRP concentration was also reduced in the ibuprofen-treated group ( pre-ibuprofen , 51 mg l-1 ; post-ibuprofen , 29 mg l-1 ; P < 0.05 ) . These results suggest that ibuprofen may have a role in abrogating the catabolic processes which contribute to weight loss in patients with pancreatic cancer The regulation of acute phase protein production and the relationship of the acute phase protein response to tumour growth was examined in colorectal cancer patients ( n = 9 ) . Ibuprofen ( 1200 mg/d ) was administered for 8 - 11 days . Following ibuprofen administration there were reductions in circulating concentrations of C-reactive protein ( P = 0.01 ) , interleukin-6 ( P = 0.06 ) , cortisol ( P = 0.04 ) and also in the platelet count ( P = 0.01 ) . There was no significant change in albumin , insulin and carcinoembryonic antigen . These results indicate that ibuprofen administered over a prolonged period substantially reduces acute protein production via its effect on interleukin-6 and cortisol . It remains to be determined whether ibuprofen is useful in moderating tumour growth in colorectal cancer patients PURPOSE A phase III , r and omized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia-lean body mass ( LBM ) , resting energy expenditure ( REE ) , and fatigue- and relevant secondary endpoints : appetite , quality of life , grip strength , Glasgow Prognostic Score ( GPS ) and proinflammatory cytokines . PATIENTS AND METHODS Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were r and omly assigned to one of five treatment arms : arm 1 , medroxyprogesterone ( 500 mg/day ) or megestrol acetate ( 320 mg/day ) ; arm 2 , oral supplementation with eicosapentaenoic acid ; arm 3 , L-carnitine ( 4 g/day ) ; arm 4 , thalidomide ( 200 mg/day ) ; and arm 5 , a combination of the above . Treatment duration was 4 months . RESULTS Analysis of variance showed a significant difference between treatment arms . A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints . An analysis of changes from baseline showed that LBM ( by dual-energy X-ray absorptiometry and by L3 computed tomography ) significantly increased in arm 5 . REE decreased significantly and fatigue improved significantly in arm 5 . Appetite increased significantly in arm 5 ; interleukin (IL)-6 decreased significantly in arm 5 and arm 4 ; GPS and Eastern Cooperative Oncology Group performance status ( ECOG PS ) score decreased significantly in arm 5 , arm 4 , and arm 3 . Toxicity was quite negligible , and was comparable between arms . CONCLUSION The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite , IL-6 , GPS , and ECOG PS score was the combination regimen that included all selected agents Abstract Under the common denomination of Systemic Immune-Metabolic Syndrome ( SIMS ) , we grouped many symptoms that share a similar pathophysiologic background . SIMS is the result of the dysfunctional interaction of tumor cells , stroma cells , and the immune system , leading to the release of cytokines and other systemic mediators such as eicosanoids . SIMS includes systemic syndromes such as paraneoplastic hemopathies , hypercalcemia , coagulopathies , fatigue , weakness , cachexia , chronic nausea , anorexia , and early satiety among others . Eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil can help in the management of persistent chronic inflammatory states , but treatment 's compliance is generally poor . Preferentially , Cox-2 inhibition can create a favorable pattern of cytokines by decreasing the production of certain eicosanoids , although their role in SIMS is unknown . The aim of this study was to test the hypothesis that by modulating systemic inflammation through an eicosanoid-targeted approach , some of the symptoms of the SIMS could be controlled . We exclusively evaluated 12 patients for compliance . Patients were assigned 1 of the 4 treatment groups ( 15- , 12- , 9- , or 6-g dose , fractionated every 8 h ) . For patients assigned to 15 and 12 doses , the overall compliance was very poor and unsatisfactory for patients receiving the 9-g dose . The maximum tolerable dose was calculated to be around 2 capsules tid ( 6 g of fish oil per day ) . A second cohort of 22 patients with advanced lung cancer and SIMS were r and omly assigned to receive either fish oil , 2 g tid , plus placebo capsules bid ( n = 12 ) or fish oil , 2 g tid , plus celecoxib 200 mg bid ( n = 10 ) . All patients in both groups received oral food supplementation . After 6 wk of treatment , patients receiving fish oil + placebo or fish oil + celecoxib showed significantly more appetite , less fatigue , and lower C-reactive protein ( C-RP ) values than their respective baselines values ( P < 0.02 for all the comparisons ) . Additionally , patients in the fish oil + celecoxib group also improved their body weight and muscle strength compared to baseline values ( P < 0.02 for all the comparisons ) . Comparing both groups , patients receiving fish oil + celecoxib showed significantly lower C-RP levels ( P = 0.005 , t-test ) , higher muscle strength ( P = 0.002 , t-test ) and body weight ( P = 0.05 , t-test ) than patients receiving fish oil + placebo . The addition of celecoxib improved the control of the acute phase protein response , total body weight , and muscle strength . Additionally , the consistent nutritional support used in our patients could have helped to maximize the pharmacological effects of fish oil and /or celecoxib . This study shows that by modulating the eicosanoid metabolism using a combination of n-3 fatty acids and cyclooxygenase-2 inhibitor , some of the signs and symptoms associated with a SIMS could be ameliorated Purpose : To test the efficacy and safety of an integrated treatment based on a pharmaconutritional support , antioxidants , and drugs , all given orally , in a population of advanced cancer patients with cancer-related anorexia/cachexia and oxidative stress . Patients and Methods : An open early-phase II study was design ed according to the Simon two-stage design . The integrated treatment consisted of diet with high polyphenols content ( 400 mg ) , antioxidant treatment ( 300 mg/d α-lipoic acid + 2.7 g/d carbocysteine lysine salt + 400 mg/d vitamin E + 30,000 IU/d vitamin A + 500 mg/d vitamin C ) , and pharmaconutritional support enriched with 2 cans per day (n-3)-PUFA ( eicosapentaenoic acid and docosahexaenoic acid ) , 500 mg/d medroxyprogesterone acetate , and 200 mg/d selective cyclooxygenase-2 inhibitor celecoxib . The treatment duration was 4 months . The following variables were evaluated : ( a ) clinical ( Eastern Cooperative Oncology Group performance status ) ; ( b ) nutritional [ lean body mass ( LBM ) , appetite , and resting energy expenditure ] ; ( c ) laboratory [ proinflammatory cytokines and leptin , reactive oxygen species ( ROS ) and antioxidant enzymes ] ; ( d ) quality of life ( European Organization for Research and Treatment of Cancer QLQ-C30 , Euro QL-5D , and MFSI-SF ) . Results : From July 2002 to January 2005 , 44 patients were enrolled . Of these , 39 completed the treatment and were assessable . Body weight increased significantly from baseline as did LBM and appetite . There was an important decrease of proinflammatory cytokines interleukin-6 ( IL-6 ) and tumor necrosis factor-α , and a negative relationship worthy of note was only found between LBM and IL-6 changes . As for quality of life evaluation , there was a marked improvement in the European Organization for Research and Treatment of Cancer QLQ-C30 , Euro QL-5DVAS , and multidimensional fatigue symptom inventory-short form scores . At the end of the study , 22 of the 39 patients were “ responders ” or “ high responders . ” The minimum required was 21 ; therefore , the treatment was effective and more importantly was shown to be safe . Conclusion : The efficacy and safety of the treatment have been shown by the study ; therefore , a r and omized phase III study is warranted . ( Cancer Epidemiol Biomarkers Prev 2006;15(5):1030–4 BACKGROUND Animal models suggest that cyclooxygenase-2 ( COX-2 ) inhibitors may be beneficial in suppressing cancer cachexia . We investigated the effect of short-course celecoxib on body composition , inflammation , and quality of life ( QOL ) in patients with cancer cachexia in a phase II clinical pilot trial . METHODS Eleven cachectic patients with head and neck or gastrointestinal cancer were r and omly assigned to receive placebo or celecoxib for 21 days while awaiting the initiation of cancer therapy . Body composition , resting energy expenditure , QOL , physical function , and inflammatory markers were measured on days 1 and 21 . RESULTS Patients receiving celecoxib experienced statistically significant increases in weight and body mass index ( BMI ) , while patients receiving placebo experienced weight loss and a decline in BMI . Patients receiving celecoxib also had increases in QOL scores . CONCLUSIONS Cachectic patients receiving celecoxib gained weight , experienced increased BMI , and demonstrated improved QOL scores . Compliance was good and no adverse events were seen |
1,656 | 29,282,010 | Conclusions HR may lead to longer OS for some selected HCC patients with PVTT than TACE , especially for type I or II PVTT , with less difference being observed for type III or IV PVTT | Background No consensus treatment has been reached for hepatocellular carcinoma ( HCC ) with portal vein tumor thrombus ( PVTT ) .
Hepatic resection ( HR ) and transarterial chemoembolization ( TACE ) have been recommended as effective options , but which is better remains unclear .
This meta- analysis is to compare the effectiveness of HR and TACE for HCC with PVTT patients . | Objectives To evaluate the outcomes of preoperative transarterial chemoembolization ( TACE ) for resectable hepatocellular carcinoma ( HCC ) with portal vein invasion . Methods From February 2006 to July 2011 , 320 patients initially diagnosed with resectable HCC and portal vein invasion were prospect ively non-r and omized into two arms . In the immediate resection arm ( Arm 1 , n = 205 ) patients received immediate surgical resection . 115 patients were included in the preoperative TACE arm ( Arm 2 ) , and eventually 85 patients underwent TACE followed by surgical resection . Results The 1- , 3- and 5-year overall survival rates were 48.3 % , 18.7 % and 13.9 % for Arm 1 and 61.2 % , 31.7 % and 25.3 % for Arm 2 ( P = 0.001 ) , respectively . In the subgroup analysis of types I and II portal vein tumour thrombus ( PVTT ) , the preoperative TACE arm demonstrated significantly better survival rates than the immediate resection arm ( PI = 0.001 , PII = 0.036 ) . However , no significant difference was found for patients with type III PVTT ( PIII = 0.684 ) . No significant difference was found between the two arms in terms of complications and mortality . Conclusions Preoperative TACE seems to confer a survival benefit for resectable HCC with PVTT , especially for types I and II PVTT , and preoperative TACE should therefore be recommended as a routine procedure . Key Points• Preoperative TACE improves the clinical outcomes for patients with PVTT• Preoperative TACE could significantly improve the rate of en bloc thrombectomy• Preoperative TACE does not increase the related adverse Background Different approaches to surgical treatment of portal vein tumor thrombosis ( PVTT ) have been advocated . This study investigated the outcomes of different surgical approaches in hepatocellular carcinoma ( HCC ) patients with PVTT . Methods We review ed prospect ively collected data for all patients who underwent hepatectomy for HCC at our hospital between December 1989 and December 2010 . Patients were excluded from analysis if they had extrahepatic disease , PVTT reaching the level of the superior mesenteric vein , or hepatectomy with a positive resection margin . The remaining patients were divided into three groups for comparison : group 1 , with ipsilateral PVTT resected in a hepatectomy ; group 2 , with PVTT extending to or beyond the portal vein bifurcation , treated by en bloc resection followed by portal vein reconstruction ; group 3 , with PVTT extending to or beyond the portal vein bifurcation , treated by thrombectomy . Results A total of 88 patients , with a median age of 54 years , were included in the analysis . Group 2 patients were younger , with a median age of 43.5 years versus 57 in group 1 and 49 in group 3 ( p = 0.017 ) . Group 1 patients had higher preoperative serum alpha-fetoprotein levels , with a median of 8,493 ng/mL versus 63.25 in group 2 and 355 in group 3 ( p = 0.004 ) , and shorter operation time , with a median of 467.5 min versus 663.5 in group 2 and 753 in group 3 ( p = 0.018 ) . No patient had thrombus in the main portal vein . Two ( 2.8 % ) hospital deaths occurred in group 1 and one ( 10 % ) in group 2 , but none in group 3 ( p = 0.440 ) . The rates of complication in groups 1 , 2 , and 3 were 31.9 , 50.0 , and 71.4 % , respectively ( p = 0.079 ) . The median overall survival duration s were 10.91 , 9.4 , and 8.58 months , respectively ( p = 0.962 ) , and the median disease-free survival duration s were 4.21 , 3.78 , and 1.51 months , respectively ( p = 0.363 ) . The groups also had similar patterns of disease recurrence ( intrahepatic : 33.8 vs. 28.6 vs. 40.0 % ; extrahepatic : 16.9 vs. 14.3 vs. 0 % ; both : 28.2 vs. 42.9 vs. 40.0 % ; no recurrence : 21.1 vs. 14.3 vs. 20.0 % ; p = 0.836 ) . Conclusions The three approaches have similar outcomes in terms of survival , complication , and recurrence . Effective adjuvant treatments need to be developed to counteract the high incidence of recurrence AIM To evaluate the efficacy of different treatment strategies for hepatocellular carcinoma ( HCC ) with portal vein tumor thrombosis ( PVTT ) and investigate factors influencing prognosis . METHODS One hundred and seventy-nine HCC patients with macroscopic PVTT were enrolled in this study . They were divided into four groups and underwent different treatments : conservative treatment group ( n = 18 ) , chemotherapy group ( n = 53 ) , surgical resection group ( n = 24 ) and surgical resection with postoperative chemotherapy group ( n = 84 ) . Survival rates of the patients were analyzed by the Kaplan-Meier method . A log-rank analysis was performed to identify group differences . Cox 's proportional hazards model was used to analyze variables associated with survival . RESULTS The mean survival periods of the patients in four groups were 3.6 , 7.3 , 10.1 , and 15.1 mo respectively . There were significant differences in the survival rates among the groups . The survival rates at 0.5- , 1- , 2- , and 3-year in surgical resection with postoperative chemotherapy group were 55.8 % , 39.3 % , 30.4 % , and 15.6 % respectively , which were significantly higher than those of other groups ( P<0.001 ) . Multivariate analysis revealed that the strategy of treatment ( P<0.001 ) and the number of chemotherapy cycles ( P = 0.012 ) were independent survival predictors for patients with HCC and PVTT . CONCLUSION Surgical resection of HCC and PVTT combined with postoperative chemotherapy or chemoembolization is the most effective therapeutic strategy for the patients who can tolerate operation . Multiple chemotherapeutic courses should be given postoperatively to the patients with good hepatic function reserve AIM To compare the therapeutic effect and significance s of multimodality treatment for hepatocellular carcinoma ( HCC ) with tumor thrombi in portal vein ( PVTT ) . METHODS HCC patients ( n=147 ) with tumor thrombi in the main portal vein or the first branch of portal vein were divided into four groups by the several therapeutic methods . There were conservative treatment group in 18 out of patients ( group A ) ; and hepatic artery ligation(HAL ) and /or hepatic artery infusion ( HAI ) group in 18 patients ( group B ) , in whom postoperative chemoembolization was done periodically ; group of removal of HCC with PVTT in 79 ( group C ) and group of transcatheter hepatic arterial chemoembolization ( TACE ) or HAI and /or portal vein infusion ( PVI ) after operation in 32 ( group D ) . RESULTS The median survival period was 12 months in our series and the 1-,3- , and 5-year survival rates were 44.3 % , 24.5 % and 15.2 % , respectively . The median survival times were 2 , 5 , 12 and 16 months in group A , B , C and D , respectively . The 1- , 3- and 5-year survival rates were 5.6 % , 0 % and 0 % in group A ; 22.2 % , 5.6 % and 0 % in group B ; 53.9 % , 26.9 % and 16.6 % in group C ; 79.3 % , 38.9 % and 26.8 % in group D , respectively . Significant difference appeared in the survival rates among the groups ( P < 0.05 ) . CONCLUSION Hepatic resection with removal of tumor thrombi and HCC should increase the curative effects and be encouraged for the prolongation of life span and quality of life for HCC patients with PVTT , whereas the best therapeutic method for HCC with PVTT is with regional hepatic chemotherapy or chemoembolization after hepatic resection with removal of tumor thrombi This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma ( HCC ) . Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospect i ve r and omized controlled trials ( RCT ) were investigated through uni‐ and multivariate analyses . None of them was suitable for radical therapies ( surgical resection , liver transplantation , or ethanol injection ) or presented end‐stage disease as reflected by an Okuda stage 3 or a Performance Status ≥3 . Sixty‐five patients were Child‐Pugh A , 34 were B , and 3 were C. Most of them exhibited a preserved Performance Status Test ( PST ) ( 0 = 56 ; 1 = 38 ; 2 = 8) . Tumor was solitary in 26 ( ≤5 cm in 16 ) and multinodular/massive in 76 . After a median follow‐up of 17 months , 79 patients died , the 1‐ , 2‐ , and 3‐year survival being 54 % , 40 % , and 28 % . The multivariate study identified PST ( P = .01 ) , constitutional syndrome ( P = .04 ) , vascular invasion ( P = .001 ) , and extrahepatic spread ( P = .04 ) as independent predictors for mortality . The 1‐ , 2‐ , and 3‐year survival for the 48 patients without adverse factors ( Stage 0 ) was 80 % , 65 % , and 50 % , respectively , and 29 % , 16 % , and 8 % in the 54 patients with at least one adverse parameter ( Stage I ) . Therefore , Stage 0 would correspond to an intermediate stage , while Stage I would represent an advanced status , before reaching an end‐stage phase . In conclusion , the outcome of nonsurgical HCC is not homogeneously grim and may be predicted by assessing the presence of symptoms and of an invasive tumoral pattern . Therapeutic trials should be design ed and evaluated considering these characteristics BACKGROUND & AIMS The Sorafenib Hepatocellular Carcinoma ( HCC ) Assessment R and omized Protocol ( SHARP ) trial demonstrated that sorafenib improves overall survival and is safe for patients with advanced HCC . In this trial , 602 patients with well-preserved liver function ( > 95 % Child-Pugh A ) were r and omized to receive either sorafenib 400 mg or matching placebo orally b.i.d . on a continuous basis . Because HCC is a heterogeneous disease , baseline patient characteristics may affect individual responses to treatment . In a comprehensive series of exploratory subgroup analyses , data from the SHARP trial were analyzed to discern if baseline patient characteristics influenced the efficacy and safety of sorafenib . METHODS Five subgroup domains were assessed : disease etiology , tumor burden , performance status , tumor stage , and prior therapy . Overall survival ( OS ) , time to progression ( TTP ) , disease control rate ( DCR ) , and safety were assessed for subgroups within each domain . RESULTS Subgroup analyses showed that sorafenib consistently improved median OS compared with placebo , as reflected by hazard ratios ( HRs ) of 0.50 - 0.85 , similar to the complete cohort ( HR=0.69 ) . Sorafenib also consistently improved median TTP ( HR , 0.40 - 0.64 ) , except in HBV-positive patients ( HR , 1.03 ) , and DCR . Results are limited by small patient numbers in some subsets . The most common grade 3/4 adverse events included diarrhea , h and -foot skin reaction , and fatigue ; the incidence of which did not differ appreciably among subgroups . CONCLUSIONS These exploratory subgroup analyses showed that sorafenib consistently improved median OS and DCR compared with placebo in patients with advanced HCC , irrespective of disease etiology , baseline tumor burden , performance status , tumor stage , and prior therapy |
1,657 | 21,483,846 | Conclusions Previous lung diseases are associated with an increased risk of lung cancer with the evidence among never smokers supporting a direct relationship between previous lung diseases and lung cancer | Background In order to review the epidemiologic evidence concerning previous lung diseases as risk factors for lung cancer , a meta- analysis and systematic review was conducted . | Background : We evaluated the relationship of Chlamydia pneumoniae infection with prospect i ve lung cancer risk using traditional serologic markers [ microimmunoflourescence ( MIF ) IgG and IgA antibodies ] and Chlamydia heat shock protein-60 ( CHSP-60 ) antibodies , a marker for chronic chlamydial infection . Methods : We conducted a nested case-control study ( 593 lung cancers and 671 controls ) within the screening arm of the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial ( N = 77,464 ) . Controls were matched to cases by age , sex , r and omization year , follow-up time , and smoking ( pack-years of smoking , time since quitting ) . We assessed C. pneumoniae seropositivity and endpoint antibody titers ( IgG and IgA against C. pneumoniae elementary bodies and IgG against CHSP-60 ) . Results : C. pneumoniae seropositivity by microimmunoflourescence IgG or IgA antibodies was not associated with lung cancer [ odds ratio of 0.88 and 95 % confidence interval ( 95 % CI ) of 0.69 - 1.13 for IgG ; odds ratio of 0.98 and 95 % CI of 0.75 - 1.27 for IgA ] . In contrast , individuals seropositive for CHSP-60 IgG antibodies had significantly increased lung cancer risk ( odds ratio , 1.30 ; 95 % CI , 1.02 - 1.67 ) , and risk increased with increasing antibody titers ( P trend = 0.006 ) . CHSP-60–related risk did not differ significantly by lung cancer histology , follow-up time , or smoking . CHSP-60 seropositivity was associated with increased risk 2 to 5 years before lung cancer diagnosis ( odds ratio , 1.77 ; 95 % CI , 1.16 - 2.71 ; P trend = 0.006 ) , thus arguing against reverse causality . Conclusions : CHSP-60 seropositivity and elevated antibody titers were associated with significantly increased risk for subsequent lung cancer , supporting an etiologic role for C. pneumoniae infection in lung carcinogenesis . Impact : Our results highlight the potential for lung cancer risk reduction through treatments targeted toward C. pneumoniae infections and chronic pulmonary inflammation . Cancer Epidemiol Biomarkers Prev ; 19(6 ) ; 1498–505 . © 2010 AACR Chinese women in Hong Kong have among the highest incidence and mortality of lung cancer in the world , in spite of a low prevalence of smoking . We carried out this population -based case – control study to evaluate the associations of previous lung disease and family cancer history with the occurrence of lung cancer among them . We selected 212 cases that were newly diagnosed with primary lung cancer , and r and omly sample d 292 controls from the community , frequency matched by age group . All the cases and controls were lifetime nonsmokers . We estimated the main effects of preexisting asthma , pulmonary tuberculosis , pneumonia , chronic bronchitis , and family lung/all cancer history , using unconditional logistic regression , accounting for various potential risk factors and confounders . All of the previous lung diseases , except chronic bronchitis , were related to an elevated risk for lung cancer , and the association with asthma was significant . Those who had more than one previous lung disease tended to be at higher risk than those with only one of them . Positive family history of any cancer was associated with over 2-fold risk than negative family history . The joint effect of positive history of previous pulmonary diseases and positive family cancer history appeared to be additive , indicating the two factors acted independently . The results support an etiological link of preexisting lung disease and family cancer history to the risk of lung cancer RATIONALE Identification of risk factors for lung cancer can help in selecting patients who may benefit the most from smoking cessation interventions , early detection , or chemoprevention . OBJECTIVE To evaluate whether the presence of emphysema on low-radiation-dose CT ( LDCT ) of the chest is an independent risk factor for lung cancer . METHODS The study used data from a prospect i ve cohort of 1,166 former and current smokers participating in a lung cancer screening study . All individuals underwent a baseline LDCT and spirometry followed by yearly repeat LDCT studies . The incidence density of lung cancer among patients with and without emphysema on LDCT was estimated . Stratified and multiple regression analyses were used to assess whether emphysema is an independent risk factor for lung cancer after adjusting for age , gender , smoking history , and the presence of airway obstruction on spirometry . RESULTS On univariate analysis , the incidence density of lung cancer among individuals with and without emphysema on LDCT was 25.0 per 1,000 person-years and 7.5 per 1,000 person-years , respectively ( risk ratio [ RR ] , 3.33 ; 95 % confidence interval [ CI ] , 1.41 to 7.85 ) . Emphysema was also associated with increased risk of lung cancer when the analysis was limited to individuals without airway obstruction on spirometry ( RR , 4.33 ; 95 % CI , 1.04 to 18.16 ) . Multivariate analysis showed that the presence of emphysema ( RR , 2.51 ; 95 % CI , 1.01 to 6.23 ) on LDCT but not airway obstruction ( RR , 2.10 ; 95 % CI , 0.79 to 5.58 ) was associated with increased risk of lung cancer after adjusting for potential cofounders . CONCLUSIONS Results suggest that the presence of emphysema on LDCT is an independent risk factor for lung cancer BACKGROUND COPD is thought to be more prevalent among men than women , a finding usually attributed to higher smoking rates and more frequent occupational exposures of significance for men . However , smoking prevalence has increased among women and there is evidence that women may be more susceptible to the adverse pulmonary function effects of smoking than men . There may also be underdiagnosis and misdiagnosis of COPD in both sexes because objective measures of lung function are underused . OBJECTIVES We undertook the present study to determine if there is gender bias in the diagnosis of COPD , such that women are less likely than men to receive a diagnosis of COPD . We also attempted to determine if underuse of lung function measurements was a factor in any bias detected . METHODS We surveyed a r and om sample of 192 primary -care physicians ( 96 American and 96 Canadian ; 154 men and 38 women ) using a hypothetical case presentation and a structured interview . The case of cough and dyspnea in a smoker was presented in six versions differing only in the age and sex of the patient . After presentation of the history and physical findings , physicians were asked to state the most probable diagnosis and to choose the diagnostic studies needed . Physicians were then presented with spirometric findings of moderate or severe obstruction without significant bronchodilator response , and the questions repeated . Finally , the negative outcome of an oral steroid trial was described . RESULTS Initially , COPD was given as the most probable diagnosis significantly more often for men than women ( 58 % vs 42 % ; p < 0.05 ) . The likelihood of a COPD diagnosis increased significantly and initial differences between sexes decreased as objective information was provided . After spirometry , COPD diagnosis rates for men and women were 74 % vs 66 % ( p = not significant ) ; after the steroid trial 85 % vs 79 % ( p = not significant ) . Only 22 % of physicians would have requested spirometry after the initial presentation . CONCLUSIONS In North America , primary -care physicians underdiagnosed COPD , particularly in women . Spirometry reduces the risk of underdiagnosis and gender bias but is underused Abstract Objectives : While 75 - 90 % of people who develop lung cancer are smokers , only a small proportion of smokers develop lung cancer . Identifying factors that increase a smoker 's risk of developing lung cancer may help scientists to better underst and the etiology of lung cancer and more effectively target high-risk groups for screening . Methods : Information on physician-diagnosed non-malignant lung diseases [ asbestosis , asthma , chronic bronchitis or emphysema ( CB/E ) , pneumonia , and tuberculosis ] was obtained at baseline from 17,698 men and women involved in CARET , a r and omized lung cancer prevention trial of beta-carotene and vitamin A among heavy smokers and asbestos-exposed workers . Hazard ratios for lung cancer were estimated through Cox regression models , after controlling for potential confounding factors , included smoking . Analyses were restricted to former and current smokers . Results : During a median follow up of 9.1 years , 1028 cases of lung cancer occurred . Those who developed lung cancer were more likely to report a history of CB/E than controls ( adjusted HR = 1.29 , 95 % CI : 1.09 - 1.53 ) . In subgroup analyses , the association between a history of CB/E and lung cancer was stronger for those who were younger at diagnosis/reference , men in the heavy smoker cohort , former smokers , and those with squamous cell carcinomas . There was little association between a history of other lung diseases and lung cancer . Conclusions : Smokers with a history of CB/E may be at higher risk of developing lung cancer , independent of their smoking history Small cell carcinoma of the lung ( SCLC ) occurs most frequently in heavy smokers , yet exhibits a lesser predominance among men than other smoking-associated lung cancers . Incidence rates have increased more rapidly in women than men and at a faster rate among women than other cell types . To investigate the importance of smoking and other risk factors , a case-control study of SCLC in women was conducted . A total of 98 women with primary SCLC and 204 healthy controls , identified by r and om-digit dialing and frequency matched for age , completed telephone interviews . Data collected include demographics , medical history , family cancer history , residence history , and lifetime smoking habits . Odds ratios ( ORs ) and 95 % confidence intervals ( 95 % CI ) were calculated using logistic regression analysis . Risk for small cell carcinoma in women is strongly associated with current use of cigarettes . Ninety-seven of 98 cases had smoked cigarettes ; 79 % of cases were current smokers and 20 % were former smokers at the time of diagnosis compared to 13 % current and 34 % former smokers among controls . The ORs associated with smoking are 108.7 ( 95 % CI 14.8 - 801 ) for ever-use of cigarettes , 278.9 ( 95 % CI 37.0 - 2102 ) for current smoking , and 31.5 ( 95 % CI 4 . 1 - 241 ) for former smoking . Risk increases steeply with pack-years of smoking and decreases with duration of smoking cessation . After adjusting for age , education , and lifetime smoking history , medical history of physician-diagnosed respiratory disease including chronic bronchitis , emphysema , pneumonia , tuberculosis , asthma , and hay fever is not associated with a significant increase in lung cancer risk . Employment in blue collar , service , or other high risk occupations is associated with a two to three-fold non-significant increase in risk for small cell carcinoma after adjusting for smoking BACKGROUND China has 1.4 million new cases of tuberculosis every year , more than any country except India . A new tuberculosis control project based on short-course chemotherapy was introduced in half the country in 1991 , after a national survey of tuberculosis prevalence in 1990 . Another survey was done in 2000 to re-evaluate the national tuberculosis burden , providing the opportunity to assess the effect of the control project . METHODS The survey in 2000 identified 375599 eligible individuals at 257 investigation points chosen from all 31 mainl and provinces by stratified r and om sampling . Children ( aged 0 - 14 years ) were suspected of having tuberculosis if they had an in duration of 10 mm or greater after a tuberculin skin test , and an abnormal fluorograph . Adults were suspected if they had a persistent cough , abnormal fluorograph , or both . Tuberculosis was diagnosed by chest radiograph , sputum-smear microscopy , and culture . FINDINGS 365097 people were examined ( 97 % of those eligible ) . Prevalences of pulmonary , culture-positive , and smear-positive tuberculosis in 2000 were 367 ( 95 % CI 340 - 397 ) , 160 ( 144 - 177 ) , and 122 ( 110 - 137 ) per 100000 population , respectively . Between 1990 and 2000 , prevalences of these three forms of the disease had fallen , respectively , by 32 % ( 5 - 68 ) , 37 % ( 7 - 66 ) , and 32 % ( 9 - 51 ) more in areas in which the project was implemented than in non-project areas . For culture-positive disease , a 30 % ( 9 - 48 ) reduction was directly attributable to the project . INTERPRETATION Between 1991 and 2000 , prevalence of tuberculosis was reduced significantly in areas of China by use of short-course chemotherapy following WHO guidelines . We estimate that in 2000 , in a population of more than half a billion , there were 382000 fewer prevalent culture-positive cases and 280000 fewer prevalent smear-positive cases than there would otherwise have been Chlamydia pneumoniae is a common respiratory pathogen that has also been associated with risk for chronic diseases , including atherosclerotic cardiovascular disease . Two recent studies have reported an association between serological evidence of past infection with the organism and lung cancer . To further evaluate this association , we conducted a case-control study among a subgroup of white male smokers identified for a population -based case-control study of lung cancer in western Washington between 1993 and 1995 . Serum specimens obtained at study enrollment from 143 cases and 147 controls were tested for C. pneumoniae IgG , IgM , and IgA antibodies . In multivariate analysis controlling for smoking variables and educational status , IgA antibody titer 216 was independently associated with risk of lung cancer among subjects < 60 years of age [ odds ratio ( OR ) , 2.67 ; 95 % confidence interval ( CI ) , 1.21 - 5.89 ] but not among older subjects ( OR , 0.69 ; 95 % CI , 0.34 - 1.43 ) . Among subjects < 60 years of age , there was suggestive evidence of a stronger association among current smokers ( OR 4.31 ; 95 % CI , 1.36 - 13.68 ) than former smokers ( OR 1.50 ; 95 % CI , 0.48 - 4.75 ; P for interaction term , 0.26 ) . Additional studies , including prospect i ve serological evaluations , are needed to further assess the possible significance of this association Epidemiological evidence suggests that airway obstruction is an independent risk factor for lung cancer and that this can not be explained by active or passive smoking alone . Chlamydia pneumoniae infection has been associated with chronic bronchitis and its exacerbates . Our aim was to evaluate the association between chronic C. pneumoniae infection and risk of lung cancer among male smokers . Smoking males with lung cancer ( n = 230 ) and their age- and locality-matched controls were selected among participants of the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study . The presence of C. pneumoniae infection was assessed by analyzing specific antibodies and immune complexes in 2 serum sample s collected with a 3-year interval before the lung cancer diagnosis . The diagnosis of chronic infection was based on stable levels of positive specific IgA antibody ( titer > or = 16 ) and immune complex ( titer > or = 4 ) . Relative risks were estimated by odds ratios ( OR ) adjusted for age , locality and smoking history by a conditional logistic regression model . Markers suggesting chronic C. pneumoniae infection were present in 52 % of cases and 45 % of controls and hence were positively associated with the incidence of lung cancer ( OR 1.6 ; 95 % confidence interval [ CI ] 1.0 - 2.3 ) . The incidence was especially increased in men younger than 60 years ( OR 2.9 ; 95 % CI 1.5 - 5.4 ) but not in the older age group ( OR 0.9 ; 95 % CI 0.5 - 1.6 ) . Before concluding that C. pneumoniae infection is a new independent risk factor for lung cancer , corroboration from other studies with larger number of cases and longer follow-up is needed The relationship between respiratory symptoms , chronic airflow limitation and respiratory cancer was examined in a r and om population sample of 876 middle-aged men . All men were examined in 1974 with interview and lung function tests . Information on respiratory cancer from 1974 to June 1985 was obtained from the Danish Cancer Register . Using a multivariate Cox regression model including age as the underlying time scale and controlling for pack-years of cigarettes , cough and breathlessness were found to be significantly related to cancer -- relative risks ( RRs ) 2.5 ( 95 % confidence interval ( CI ) : 1.3 - 5.0 ) and 2.2 ( 95 % CI : 1.0 - 4.9 ) , respectively . Phlegm , chronic phlegm , and chronic bronchitis were not related to respiratory cancer after controlling for age and smoking . Forced expiratory volume in one second ( FEV1 ) was related to respiratory cancer , RR = 2.1 ( 95 % CI : 1.3 - 3.4 ) per litre under the expected FEV1 given height . Thus , our study demonstrates some relationship between respiratory symptoms and FEV1 and respiratory cancer ; however , the study at the same time questions the previously demonstrated relationship between phlegm and respiratory cancer Background : Guidelines and st and ards for diagnosis and management of chronic obstructive pulmonary disease ( COPD ) have been presented by different national and international societies , but the spirometric criteria for COPD differ between guidelines . Objectives : To estimate prevalence of COPD using the guidelines of the British Thoracic Society ( BTS ) , the European Respiratory Society ( ERS ) , the Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) , and the American Thoracic Society ( ATS ) . Further , to evaluate reported airway symptoms , contacts with health care providers , and physician diagnosis of COPD in relation to the respective criteria , and gender differences . Method : In 1992 a postal question naire was sent to a r and om sample of adults aged 20–69 years , 4,851 ( 85 % ) out of 5,681 subjects responded . In 1994–1995 a r and om sample of the responders , 970 subjects , were invited to a structured interview and a lung function test ; 666 ( 69 % ) participated . Results : The prevalence of COPD was 7.6 , 14.0 , 14.1 , 12.2 and 34.1 % according to BTS , ERS , GOLD , clinical ATS ( with symptoms or physician diagnosis ) , and spirometric ATS criteria , respectively . Prevalent COPD was related to age , smoking habits and family history of obstructive airway disease but not to gender . Physician diagnosis of chronic bronchitis or emphysema was only reported by 16.3 , 12.2 , 11.0 , 23.4 and 8.2 % of subjects fulfilling the respective criteria , though a majority reported airway symptoms . Conclusion : The main determinants for prevalent COPD were age , smoking habits and spirometric criteria of COPD . Though a majority reported airway symptoms and contact with health care providers due to respiratory complaints , only a minority was diagnosed as having COPD , indicating a large underdiagnosis |
1,658 | 25,780,780 | Conclusions .
LMWH is as safe and effective as UFH . | Background .
Low molecular weight heparin ( LMWH ) is an effective anti-coagulant for thrombotic events .
However , due to its predominant renal clearance , there are concerns that it might be associated with increased bleeding in patients with renal disease .
Objectives .
We systematic ally evaluated the efficacy and safety of LMWH compared to unfractionated heparin ( UH ) in end stage renal disease ( ESRD ) patients . | The efficacy and safety of a low molecular weight heparin ( LMWH ) given as a single predialysis bolus injection was compared to st and ard heparin ( SH ) administered with a continuous infusion in a r and omized , 6 month , open follow-up study in 70 patients undergoing hemodialysis . No major bleeding or adverse events were encountered during a total of 4,000 dialysis procedures ( 2,000 with LMWH ) . Clot formation in the extracorporeal circuit was minimal and comparable between the groups at 4 , 13 , and 26 weeks after the start of the study . No accumulation of LMWH anticoagulant activity was noted . It is concluded that the use of LMWH is a safe , effective , and less complex alternative to SH Low molecular weight heparins ( LMWHs ) are used for prevention of clotting in the dialysis circuit . The aim of this trial was to define the optimal dose of a new LMWH and to test the efficiency of a single dose at the start of the session . Fifteen patients were treated according to a double blind and crossover design during 4 blocks of 5 consecutive reviparin doses assigned r and omly as 50 , 60 , 70 , 85 , and 100 IU anti-Xa/kg . Assessment was carried out on screening of fibrin rings or clots in the arterial and venous air traps and on visual detection of fiber in the dialyzer after rinsing . These clinical results were compared to plasmatic anti-Xa activity and thrombin-antithrombin ( TAT ) complex generation . A st and ard dose of 70 IU anti-Xa/kg of nadroparin was used as the control . After a bolus of 50 to 100 IU anti-Xa/kg , the occurrence of fibrin rings and clots in the air traps was dependent on three factors : dose of LMWH , time of the session , and patient status . A bolus of 85 IU anti-Xa/kg of reviparin was effective and safe for sessions of 4 h. For this dose , plasmatic anti-Xa activity was 0.96 + /- 0.28 IU/ml at Hour 2 and 0.82 + /- 0.22 IU/ml at Hour 4 . TAT complexes are good markers of the activation of the coagulation . They did not increase during a 4 h session after a reviparin bolus of 100 IU/kg . For the same LMWH dose , the trial shows a great variability of the clinical effect and anti-Xa activities from one patient to another . A single dose of 85 IU anti-Xa/kg of reviparin can be used at the start of the dialysis session as a loading dose . We advise adapting the dose during the subsequent sessions according to the appearance of the blood circuit . The benefit of monitoring anti-Xa activity and TAT complexes could be tested in a further trial We have performed a dose ranging study of a low MW heparin , Kabi 2165 , during haemodialysis in humans ( n = 16 ) and compared it to a dose of unfractionated commercial heparin that has already been shown to inhibit fibrin formation . Low MW heparin administered as 5000 or 10,000 anti-factor Xa units , s.c . , half an hour prior to the initiation of dialysis was unable to prevent fibrin formation in the dialyser circuit . A single bolus injection of 5000 anti-factor Xa units of low MW heparin given i.v . inhibited fibrin formation , as determined by FPA generation , for up to 4 h and permitted dialysis for 6 h. Such a bolus injection may be useful for short frequent dialyses . Infusion of low MW heparin in the same dosage regimen as unfractionated heparin , 5000 anti-factor Xa units bolus plus 1500 anti-factor Xa units/h , result ed in a progressive rise in heparin , caused by its longer half-life of elimination from the circulation , and almost completely suppressed both FPA generation and fibrin clot formation for 6 h dialysis . From these studies we calculate that infusion of this low MW heparin at a dose of approximately 4000 anti-factor Xa units bolus plus 750 anti-factor Xa units/h should be a useful regimen that will be effective in suppressing fibrin formation during prolonged dialysis , and the plasma anti-factor Xa level of low MW heparin may reflect its ability to inhibit fibrin formation , although exactly comparable anti-factor Xa levels of unfractionated commercial heparin and low MW heparins may not have identical inhibitory effects Ten patients on chronic intermittent hemodialysis treatment received either unfractionated heparin or low molecular weight ( LMW ) heparin K 2165 in a single-blinded r and omized cross-over study to assess : effects on hemostasis and ex vivo platelet functions , and effectiveness , i.e. prevention of fibrin formation in the extracorporeal circuit . The 20 dialysis treatments were without untoward side effects , for both drugs used . The variation in the plasma anti-Xa activities was significantly less during K 2165 treatment than during heparinization . No differences between the drugs were observed regarding the Ivy bleeding time , platelet count and platelet aggregation ( spontaneous , and induced by ADP and collagen ) . Plasma platelet factor 4 levels did not increase under K 2165 to such an extent as under heparin . Both drugs did not influence the plasma levels of beta-thromboglobulin , thromboxane B2 and platelet serotonin content . K 2165 did not affect platelet adhesion to collagen , in contrast to heparin which substantially inhibited platelet adhesion . Under both treatments , 4 minor clots were observed in 4 artificial kidneys , despite plasma anti-Xa levels in between 0.19 and 0.46 U/ml . K 2165 may therefore be considered as effective an anticoagulant as heparin , with less effects on ex vivo platelet functions BACKGROUND Increased platelet reactivity presages adverse cardiac events . Because both haemodialysis and unfractionated heparin ( UFH ) can increase platelet reactivity , we compared platelet reactivity during haemodialysis when patients were anticoagulated with UFH or enoxaparin . METHODS Patients ( n = 20 ) underwent consecutive haemodialysis sessions with either UFH or enoxaparin in a r and om order . Blood was taken from the arterial end of the haemodialysis circuit at the initiation of haemodialysis before anticoagulation . Subsequently , blood was taken during dialysis from the venous end of the circuit 10 min after treatment with UFH or enoxaparin . Platelet reactivity was assessed with the use of flow cytometry by determining the capacity of platelets to bind fibrinogen and the surface expression of P-selectin in response to adenosine diphosphate ( ADP , 0 and 0.2 microM ) . Results were compared with the use of two-way repeated measure ANOVA . RESULTS Platelet reactivity in arterial blood obtained at the beginning of dialysis prior to patients being treated with either UFH [ 0.2 microM ADP-induced capacity to bind fibrinogen = 28+/-15 % ( SD ) ] or enoxaparin ( 30+/-18 % ) was similar ( P = 0.15 ) . In contrast , platelet reactivity was less after treatment with enoxaparin compared with UFH ( P = 0.006 ) . The 0.2 microM ADP-induced capacity to bind fibrinogen in venous blood obtained 10 min after anticoagulation was 34+/-11 % after treatment with UFH and 22+/-11 % after treatment with enoxaparin . CONCLUSIONS Anticoagulation with enoxaparin during haemodialysis is associated with less platelet reactivity compared with UFH . Accordingly , enoxaparin use may contribute to a lesser risk of cardiac events in patients with end-stage renal disease treated with haemodialysis Background : Low-molecular-weight heparins offer several advantages over st and ard heparins , but their use for maintenance hemodialysis has been limited in North America because of their higher cost . Our objective was to compare tinzaparin to st and ard heparin during maintenance hemodialysis over an 8-week period , in regard to the visual aspect of the extracorporeal circuit , filter reuse , bleeding and time for compression of vascular access at the end of hemodialysis session , nursing time devoted to anticoagulation administration , level of satisfaction of patients and nurses , and relative cost . Methods : Thirty-two chronic hemodialysis adult patients with peripheral accesses were r and omly divided into two groups in a cross-over design : tinzaparin for 4 weeks followed by st and ard heparin for 4 weeks , or vice versa . Hemodialysis was performed thrice weekly over 3.5–4 h using large surface reused filters . St and ard heparin was administered as an initial bolus of 50–75 units per kilogram followed by an infusion to maintain an activated clotting time ( ACTESTER ) between 150 and 200 s and discontinued 30–45 min before the end of the session . The initial dose of tinzaparin was 3,500 IU anti-Xa for patients usually receiving 7,500 units or less of st and ard heparin , or 4,500 IU anti-Xa for patients receiving more than 7,500 units of st and ard heparin , and it was injected as a bolus in the arterial line at the beginning of hemodialysis . Dosage adjustments were made by increments or decrements of 500 IU . Results : A total of 6 patients did not require any adjustment in their dose of tinzaparin and remained at the initial dose , while the remaining 26 necessitated adjustments of the initial dose of tinzaparin : 20 patients required increments from the initial dose whereas 6 required reductions . For most patients , 27 of them , the st and ard heparin dose was kept at the same level throughout the study period ( since it was their usual regimen and they were in stable medical conditions ) . According to the monitoring scale , the visual aspects of the tubing of the extracorporeal circuit and of the dialyzers at the end of the session were similar for both tinzaparin and st and ard heparin . The time of compression of the vascular access at the end of the hemodialysis sessions was not significantly different with tinzaparin than with st and ard heparin . However , as indicated below , most patients noted less bleeding ( or oozing ) from their access ( during compression and thereafter , in the few hours after hemodialysis ) with tinzaparin than with st and ard heparin . Clotting was observed more frequently in the arterial and venous bubble traps with tinzaparin than with st and ard heparin . The presence of clot(s ) was observed in the arterial and venous bubble traps in , respectively , 18 ± 12 and 10 ± 6 % of the sessions with tinzaparin , while in , respectively , 3 ± 4 and 2 ± 4 % of the sessions with st and ard heparin ( p < 0.005 ) . Despite a tendency for a reduced reuse number of the dialyzers , the difference did not reach statistical significance . Among the 30 patients who completed the study , 2 reported excessive bleeding from their vascular access with tinzaparin whereas 8 reported such an excessive bleeding with st and ard heparin . The level of satisfaction of patients and nurses for tinzaparin was extremely good . The main reasons stated by the patients was reduced bleeding from their access after dialysis . The nurses preferred tinzaparin because of the simplicity and the rapidity of its administration , the lack of monitoring required , and the decreased bleeding/oozing tendency from the vascular access sites . The time spent for anticoagulation during a hemodialysis session was reported as 5 min with st and ard heparin ( if no ACTESTER monitoring ) , 25–30 min with st and ard heparin ( if ACTESTER monitoring required ) , and 1 min with tinzaparin . The cost analysis revealed that although tinzaparin is more than six times more expensive than st and ard heparin , the use of tinzaparin becomes similar to the use of st and ard heparin ( USD 7.33 vs. USD 7.62 Canadian dollars for one hemodialysis session ) if ACTESTER monitoring is performed ( assuming that 22 % of the sessions are routinely monitored and that one ACTESTER device is necessary for 8–10 dialysis stations , as applied in our unit ) . Conclusion : Our experience with tinzaparin was positive : it represents a simple and easy way to offer anticoagulation during maintenance hemodialysis , it seems associated with less postdialysis bleeding , it saves precious nursing time and is widely appreciated by patients and staff In haemodialysis low-molecular-weight ( LMW ) heparin is increasingly used for anticoagulation . The advantages over unfractionated ( UF ) heparin are the lower bleeding risk and the lack of influence on lipid metabolism . However , no reliable and rapid method is available so far to control the efficacy and safety of LMW heparin during haemodialysis . The specific anti-factor Xa ( aXa ) chromogenic substrate assays are laborious and time consuming . In the present study we have compared chromogenic assay with a coagulation assay ( heptest ) , which was performed from plasma and whole-blood sample s. The effects were compared with unfractionated heparin during haemodialysis . The aXa activity in the chromogenic S2222 assay ranged between 0.2 and 0.5 U/ml with UF heparin and between 0.4 and 0.8 U/ml with LMW heparin during haemodialysis . The coagulometric aXa activity in heptest assay from plasma was 0.6 - 1.0 U/ml with UF heparin and 1.2 - 2.0 U/ml with LMW heparin . The Heptest coagulation values from citrated whole blood sample s ranged from 0.4 to 0.8 U/ml with UF heparin and from 0.8 to 1.4 U/ml with LMW heparin . The prolongation of the heptest clotting times with UF and LMW heparin was in the range of 4.4 for UF heparin and 5.2 for LMW heparin using the whole-blood assay . Heptest assay from plasma sample s yielded prolongations of 6.1 with UF heparin and 6.6 with LMW heparin . The data show that the coagulation assay is rapid and reproducible using plasma or uncentrifuged whole-blood sample s and is valid to monitor UF heparin or LMW heparin in patients undergoing chronic intermittent haemodialysis BACKGROUND Low-molecular-weight heparin ( LMWH ) has been suggested as providing safe , efficient , convenient and possibly more cost-effective anticoagulation for haemodialysis ( HD ) than unfractionated heparin , with fewer side-effects and possible benefits on uraemic dyslipidaemia . METHODS In this prospect i ve , r and omized , cross-over study we compared the safety , clinical efficacy and cost effectiveness of Clexane ( enoxaparin sodium ; Rhône-Poulenc Rorer ) with unfractionated heparin in 36 chronic HD patients . They were r and omly assigned to either Clexane ( 1 mg/kg body weight , equivalent to 100 IU ) or st and ard heparin , and followed prospect ively for 12 weeks ( 36 dialyses ) before crossing over to the alternate therapy for a further 12 weeks . Heparin anticoagulation was monitored using activated coagulation times . RESULTS Dialysis with Clexane result ed in less frequent minor fibrin/clot formation in the dialyser and lines than with heparin ( P<0.001 ) , but was accompanied by increased frequency of minor haemorrhage between dialyses ( P<0.001 ) . Clexane dose reduction ( to a mean of 0.69 mg/kg ) eliminated excess minor haemorrhage without increasing clotting frequencies . Mean vascular compression times were similar in both groups . Over 24 weeks , no changes in st and ard serum lipid profiles were observed . CONCLUSIONS This study suggests that a single-dose protocol of Clexane is an effective and very convenient alternative to sodium heparin , but currently direct costs are about 16 % more . We recommend an initial dose of 0.70 mg/kg BACKGROUND During haemodialysis ( HD ) , polymorphonuclear cells ( PMNs ) and platelets are activated and release various granule products , including myeloperoxidase ( MPO ) and platelet factor 4 ( PF4 ) . MPO triggers the generation of reactive oxygen species , leading to irreversible protein , carbohydrate and lipid modification . PF4 probably also contributes to oxidative stress . As previously shown , HD-induced PMN degranulation is almost completely abolished during citrate anticoagulation , most probably due to its calcium chelation ability . METHODS In the present study , apart from HD-induced PMN and platelet degranulation , oxidative stress was analysed during three modes of anticoagulation . Heparin , dalteparin and citrate ( HDhep , HDdal and HDcit ) were compared in a r and omized , crossover fashion in eight chronic HD patients . Multiple blood sample s were taken during the third HD session of each modality , from both the afferent and efferent line . Besides the degranulation markers MPO and PF4 , various markers of oxidative stress were measured , including oxidized low-density lipoprotein ( ox-LDL ) , malondialdehyde ( MDA ) and carboxymethyllysine ( CML ) . RESULTS During HDhep and HDdal , marked degranulation was observed shortly after the start of HD . In contrast , during HDcit , PF4 and MPO levels remained unaltered , suggesting no release at all . After 1 week of HDcit , ox-LDL levels were markedly reduced [ median 26 % ( 3 - 65 % ) , P=0.01 ] , if compared with HDhep and HDdal . As regards MDA and CML , no differences were found . CONCLUSIONS This study shows first , that HD-induced PMN and platelet degranulation are early , most probably calcium-dependent processes and , secondly , that the formation of ox-LDL is clearly dependent on the type of anticoagulant applied In a r and omized crossover trial , we compared a simple citrate anticoagulation protocol for high-flux hemodialysis with st and ard anticoagulation by low-molecular-weight heparin ( dalteparin ) . Primary end points were urea reduction rate ( URR ) , Kt/V , and control of electrolyte and acid-base homeostasis . Secondary end points were bleeding time at vascular puncture sites and markers of activation of platelets , coagulation , and fibrinolysis . Solute removal during citrate dialysis was excellent ( URR , 0.71 + /- 0.06 ; Kt/V , 1.55 + /- 0.3 ) and similar to results of conventional bicarbonate hemodialysis anticoagulation with dalteparin ( URR , 0.72 + /- 0.04 ; Kt/V , 1.56 + /- 0.2 ) . Electrolyte control was effective with both anticoagulation regimens , and total and ionized calcium , sodium , potassium , and phosphate concentrations at the end of dialysis did not differ . Alkalemia was less frequent after citrate than conventional dialysis ( pH 7.5 in 25 % versus 62 % of patients ; mean pH at end of dialysis , 7.46 + /- 0.06 versus 7.51 + /- 0.07 ; P < 0.01 ) . Bleeding time at puncture sites was shorter by 30 % after citrate compared with dalteparin anticoagulation ( 5.43 + /- 2.80 versus 7.86 + /- 2.93 minutes ; P < 0.001 ) . Activation of platelets , coagulation , and fibrinolysis was modest for both treatments and occurred mainly within the dialyzer during dalteparin treatment and in the vascular-access region during citrate anticoagulation . Citrate-related adverse events were not observed . We conclude that citrate anticoagulation for high-flux hemodialysis is feasible and safe using a simple infusion protocol In 20 hemodialysis patients using mainly flat plate dialyzers , we have conducted a controlled r and omized crossover trial of three dose regimens of a low molecular weight heparin ( LMWH ) , " Fragmin " ( Kabi 2165 ) , in comparison with a st and ard dose regimen of commercial unfractionated heparin ( UFH ) that had previously been shown to provide effective anticoagulation . The aim of the present study was to find the lowest dosage regimen of the LMWH which would be as effective as the st and ard UFH regimen . The UFH regimen comprised a prime with heparinized saline , an initial intravenous bolus of 5,000 international units ( IU ) and an infusion of 1,500 IU/h . The three LMWH regimens comprised a LMWH-saline prime , an infusion of 750 anti-factor Xa ( aXa ) U/h and three different bolus doses : 1 ) LMWH-low : 3,000 aXa U. 2 ) LMWH-medium : 4,000 aXa U. 3 ) LMWH-high : 5,000 aXa U. With the UFH regimen , plasma heparin levels of around 1.0 IU/ml were maintained during the heparin infusion , declining to 0.71 IU/ml an hour after the infusion was terminated . The LMWH-medium regimen produced very similar plasma aXa levels . The LMWH-high regimen also produced similar plasma aXa levels : therefore , it had no advantage over the LMWH-medium regimen . The LMWH-low regimen produced significantly lower levels than the other regimens during the heparin infusion ( 0.81 - 0.85 aXa U/ml , p less than 0.025 ) . Dialysis proceeded uneventfully at all times and plasma levels of fibrinopeptide A ( FPA ) were suppressed well with all 4 regimens ( 2.77 - 5.74 pmol/ml ) but tended to rise after the infusion was switched off ( 5.52 - 8.45 pmol/ml ) . ( ABSTRACT TRUNCATED AT 250 WORDS STUDY OBJECTIVE To compare the frequency of bleeding complications from enoxaparin in patients with normal renal function versus patients with renal insufficiency . DESIGN Retrospective chart review . SETTING University-based tertiary care center . PATIENTS One hundred six patients who received two or more doses of enoxaparin . MEASUREMENTS AND MAIN RESULTS Total bleeding complications occurred in 22 % of patients with normal renal function and 51 % with renal insufficiency ( p<0.01 ) . Major bleeds were also significantly different , 2 % and 30 % , respectively ( p<0.001 ) . No patients with normal renal function were given fresh-frozen plasma or packed red blood cells , whereas in those with renal insufficiency , 13 % and 32 % , respectively , received these products ( p<0.01 ) . CONCLUSION Enoxaparin may have result ed in increased bleeding complications and use of blood products in patients with renal insufficiency . Prospect i ve studies need to be conducted to define the drug 's role and dosage adjustments in these patients Cardiovascular disease is one of the major causes of death in hemodialysis patients and seems to be related , at least in part , to lipid abnormalities . It has been suggested that in these patients low-molecular-weight heparin ( LMWH ) is superior to conventional heparin because it causes less side effects and has beneficial effects on lipid parameters . Our study was carried out to examine the long-term effects of the replacement of conventional heparin by LMWH on the lipoprotein profile in a large group of hemodialysis patients . A total of 76 patients aged 15 - 61 years receiving hemodialysis for 48 ( range 10 - 169 ) months were studied . In all patients administration of LMWH was introduced in doses of 2,500 - 5,000 anti-factor Xa units for 12 months . Then , we r and omly switched half of the patients back to conventional heparin for another 12 months , while the remaining patients continued to receive LMWH for 12 months . In the whole group of patients the use of LMWH instead of conventional heparin was followed by a significant decrease in serum total cholesterol , triglyceride and apoprotein B levels . The continued use of LMWH for another 12 months in half of the patients was followed by a further significant improvement in the lipid profile . In contrast , no significant changes in serum lipid parameters were observed in patients switched back to conventional heparin . In conclusion , the use of LMWH instead of conventional heparin for anticoagulation during hemodialysis is followed by an improvement in lipid profile , which is evident only after long-term treatment Background and aims . Heparin modulates function of vascular endothelial cells . We studied the effects of unfractionated heparin ( UFH ) versus low-molecular-weight heparin ( LMWH ) , enoxaparin , used as anticoagulants during hemodialysis ( HD ) on plasma levels of circulating endothelium-derived molecules : thrombomodulin ( TM ) , von Willebr and factor ( vWF ) , plasminogen activator inhibitor-1 ( PAI-1 ) , cell surface adhesion molecules ( E-selectin ) , intercellular adhesion molecule-1 ( ICAM-1 ) , and prothrombin fragment 1 + 2 ( PF 1 + 2 ) . Methods . Twenty-five patients undergoing enoxaparin-anticoagulated HD were r and omly assigned either to continue enoxaparin ( n = 13 ) or receive UFH ( n = 12 ) during HD and followed prospect ively for 12 weeks . Plasma immunoreactive TM , vWF , PAI-1 , ICAM-1 , E-selectin , and PF 1 + 2 were measured before the r and omization procedure and after 12 weeks , at the start , after 10 and 180 minutes of HD . Results . The switch from LMWH to UFH result ed in decreased pre-HD levels of PAI-1 and TM and increased PF 1 + 2 concentrations . Predialysis PAI-1 negatively correlated with the total dose of UFH/kg/HD . No significant differences were observed in the other variables before and during HD after switching from LMWH to UFH . During enoxaparin-anticoagulated HD , only plasma PAI-1 levels decreased by 32 % after 180 minutes compared with the baseline values . This percentage decrease positively correlated with predialysis PAI-1 levels and marginally with PF 1 + 2 concentrations after 180 minutes of enoxaparin-anticoagulated HD . Conclusion . Enoxaparin-anticoagulated HD is related to transient plasma PAI-1 decrease , whereas UFH anticoagulation may be the cause of delayed PAI-1 and TM depletion , which is an untoward consequence of enhanced coagulation activity in chronic HD patients Aldosterone suppression and subsequent hyperkalemia are well described reversible side effects of prolonged treatment with heparin . This study was design ed to examine whether the discontinuous use of heparin three times a week to prevent thrombosis formation during hemodialysis sessions could also induce hypoaldosteronism and might contribute to increased predialysis kalemia in hemodialysis patients . Two different heparinization regimens were prospect ively compared in a crossover study of 11 chronic hemodialysis patients . During 2 consecutive weeks , the patients were dialyzed each week with either their usual doses of unfractionated heparin ( UH ) ( 6,160 IU + /- 1,350 IU ) or low molecular weight heparin ( LMWH ) ( 15 anti-Xa activity [ aXa ] U/kg + 5 aXa U/kg/h ) . In all but 2 patients , the predialysis level of plasma K+ was higher with UH than with LMWH , and the mean value was higher ( 5.66+/-0.83 versus 5.15+/-0.68 mM , p = 0.01 ) while no differences in the predialysis plasma concentrations of creatinine , phosphate , urea , and bicarbonate were observed , excluding the potential role of differences in diet and dialysis efficacy in explaining the higher plasma K+ concentration with UH . The mean plasma aldosterone to plasma renin activity ( pRA ) ratio was higher with LMWH than with UH ( 149.54+/-123.1 versus 111.91+/-86.22 pg/ng/ h , p < 0.05 ) . Individual plasma aldosterone values were found to be correlated to pRAs both during the UH period and the LMWH period , and the slope of the positive linear relation between plasma aldosterone and pRA was lower during the UH treatment period ( 63 versus 105 pg/ng/h ) . Finally , a negative linear correlation was found between the differences in individual predialysis plasma K+ observed during the 2 protocol s and the differences in the corresponding plasma aldosterone levels , suggesting a link between the higher kalemia and the lower aldosterone responsiveness to angiotensin with unfractionated heparin . Although it can not be concluded whether or not LMWH inhibits aldosterone synthesis , should LMWH decrease aldosterone production , this side effect is 33 % less marked than that of UH so that the predialysis plasma K+ levels are 10 % lower . This property makes LMWH use preferable to that of UH in patients with elevated predialysis kalemia BACKGROUND Heparin inhibits prothrombotic tissue factor ( TF ) and releases its inhibitor , tissue factor pathway inhibitor ( TFPI ) , from the endothelium , but repeated administration of heparin depletes vascular stores of TFPI . We studied the anticoagulant effects of unfractionated heparin ( UFH ) vs low-molecular-weight enoxaparin-used for thrice-weekly maintenance haemodialysis (HD)-on plasma levels of total TF and TFPI and on those of an activated coagulation marker prothrombin fragment 1 + 2 ( PF 1 + 2 ) . METHODS Twenty-five patients dialysed using a single injection of enoxaparin ( at a mean dose of 0.68 mg/kg ) were r and omly assigned to either receive UFH administered as a mean bolus of 42.1 IU/kg and continuous infusion of 57.8 IU/kg ( n=12 ) or to be maintained on enoxaparin ( n=13 ) , and were followed prospect ively for 12 weeks . Plasma immunoreactive TF , TFPI and PF 1 + 2 were measured at the start and after 10 and 180 min of HD , and compared with values in 15 healthy controls . RESULTS Pre-dialysis TF , TFPI and PF 1 + 2 were higher than normal ( all P<0.0001 ) . TF and PF 1 + 2 did not change , while TFPI levels , compared with baseline , increased at each interval in enoxaparin-anticoagulated HD patients ( all P<0.0001 ) . TFPI increments correlated inversely with pre-dialysis TFPI ( both P<0.0007 ) . In patients switched to UFH , TF levels remained unchanged compared with pre-r and omization values , TFPI increased at each interval of HD sessions ( all P<0.035 ) and PF 1 + 2 increased pre-dialysis ( P=0.015 ) . The over-dialysis effects of UFH resembled those of enoxaparin . In contrast , baseline TFPI and its 10-min rise correlated inversely with the UFH loading dose ( both P<0.040 ) . Pre-dialysis PF 1 + 2 was inversely associated with TFPI increments ( both P<0.034 ) , and directly with pre-dialysis TFPI ( P=0.018 ) and the UFH loading dose ( P=0.045 ) . CONCLUSIONS Depletion of heparin-releasable stores of TFPI is an untoward effect of repeated anticoagulation during maintenance HD therapy . The traditional UFH regimen is more prothrombotic than single enoxaparin injections , with high loading doses of UFH being involved in TFPI exhaustion and subsequent hypercoagulability CONTEXT Obesity and diabetes are increasing in the United States . OBJECTIVE To estimate the prevalence of obesity and diabetes among US adults in 2001 . DESIGN , SETTING , AND PARTICIPANTS R and om-digit telephone survey of 195 005 adults aged 18 years or older residing in all states participating in the Behavioral Risk Factor Surveillance System in 2001 . MAIN OUTCOME MEASURES Body mass index , based on self-reported weight and height and self-reported diabetes . RESULTS In 2001 the prevalence of obesity ( BMI > or = 30 ) was 20.9 % vs 19.8 % in 2000 , an increase of 5.6 % . The prevalence of diabetes increased to 7.9 % vs 7.3 % in 2000 , an increase of 8.2 % . The prevalence of BMI of 40 or higher in 2001 was 2.3 % . Overweight and obesity were significantly associated with diabetes , high blood pressure , high cholesterol , asthma , arthritis , and poor health status . Compared with adults with normal weight , adults with a BMI of 40 or higher had an odds ratio ( OR ) of 7.37 ( 95 % confidence interval [ CI ] , 6.39 - 8.50 ) for diagnosed diabetes , 6.38 ( 95 % CI , 5.67 - 7.17 ) for high blood pressure , 1.88 ( 95 % CI,1.67 - 2.13 ) for high cholesterol levels , 2.72 ( 95 % CI , 2.38 - 3.12 ) for asthma , 4.41 ( 95 % CI , 3.91 - 4.97 ) for arthritis , and 4.19 ( 95 % CI , 3.68 - 4.76 ) for fair or poor health . CONCLUSIONS Increases in obesity and diabetes among US adults continue in both sexes , all ages , all races , all educational levels , and all smoking levels . Obesity is strongly associated with several major health risk factors Background : To compare st and ard heparin ( SH ) and low molecular weight heparin ( LMWH ) in terms of anticoagulation , platelet activation and lipid metabolism , we selected 54 patients who had been on 4-hour hemodialysis three times weekly for at least 12 months , without bleeding disorders or dyslipidemic diseases . 28 were on hemodialysis with Polysulfone low-flux , 26 were on hemodiafiltration with Polysulfone high-flux . All patients underwent EPO . Methods : During the first 18 months , we administered SH 1,500 IU on starting dialysis and 1,500 ± 500 IU in continuous intradialytic infusion per session . In the following 18 months , we administered LMWH 64.6 IU/kg on starting dialysis in a single arterious bolus . We assessed aPTT , anti-factor Xa activity , TAT and FPA , β-TG and PF4 . Blood sample s were taken monthly at times 0 , 30 , 60 , 180 and 240 min , as well as 1 , 4 and 20 h after dialysis end . Predialysis cholesterol , HDL , LDL , triglycerides and lipoprotein(a ) were checked monthly . Results : During both LMWH and SH sessions no clotting or major bleeding complications were observed . APTT with LMWH was lower than that found with SH ( p < 0.001 ) ; aFXa using LMWH was higher than when using SH ( p < 0.001 ) ; TAT and FPA were lower in LMWH sessions ( p < 0.01 ) than in SH sessions . We also detected lower β-TG ( p < 0.05 ) and PF4 levels ( p < 0.05 ) using LMWH than using SH . As regards lipids , we only observed a significant decrease in triglycerides after 18 months of LMWH treatment . Conclusions : Routine use of LMWH during hemodialysis affords a safe and effective alternative to SH , and causes reduced platelet activation BACKGROUND We aim ed to compare the effect of unfractionated heparin ( UFH ) and enoxaparin used as anticoagulants during hemodialysis ( HD ) on circulating levels of heparin-binding , endothelial-derived , proangiogenic factors-vascular endothelial ( VEGF(165 ) ) and basic fibroblast ( bFGF ) growth factor . METHODS We enrolled 22 chronic HD patients , who were r and omly assigned to either enoxaparin ( n=11 ) or UFH ( n=11 ) anticoagulation , and followed prospect ively for 12 weeks before crossing over to the alternate therapy for further 12 weeks . The cytokines were measured by immunoassay at the start , at 10 and 180min of HD . RESULTS The baseline VEGF(165 ) and bFGF levels were comparable during enoxaparin and UFH treatment . VEGF(165 ) significantly decreased during both enoxaparin ( chi(2 ) ANOVA=33.0 , P<10(-6 ) ) and UFH ( chi(2 ) ANOVA=27.2 , P<10(-6 ) ) anticoagulated HD , while over-HD bFGF remained stable regardless of the type of heparin . The switch from enoxaparin to UFH treatment was connected with 34 % VEGF(165 ) decrease after 180min of HD and had no impact on bFGF . During UFH-anticoagulated HD 75 % VEGF(165 ) decrease after 10min was negatively associated with heparin dosage and was more profound in patients with ischemic heart disease . CONCLUSION The traditional UFH regimen , in contrast to enoxaparin treatment , is connected with dose-depended VEGF(165 ) decrease during HD procedure . The biological and possible clinical relevance of this observation requires further investigations BACKGROUND Unfractionated heparin ( UFH ) and low molecular weight heparin constitute fundamental anticoagulants during hemodialysis ( HD ) . We aim ed to investigate the effect of UFH and enoxaparin on plasma levels of prothrombin fragment 1 + 2 ( PF 1 + 2 ) and thrombin/antithrombin complex ( TAT ) as markers of intravascular thrombogenesis during HD . METHODS We enrolled 22 chronic HD patients , who were r and omly assigned to either iv enoxaparin ( n=11 ) or UFH ( n=11 ) anticoagulation , and followed prospect ively for 12 weeks before crossing over to the alternate therapy for further 12 weeks . Plasma levels of PF 1 + 2 and TAT were measured by immunoassay at the start , at 10 and 180 min of HD session after each period of evaluation . RESULTS The baseline PF 1 + 2 and TAT levels were comparable under enoxaparin and UFH treatment . PF 1 + 2 significantly decreased during both UFH ( chi(2 ) ANOVA=9.82 , P=0.007 ) and enoxaparin ( chi(2 ) ANOVA=29.40 , P<10(-6 ) ) anticoagulated HD , while over-HD TAT levels changes differed depending on the type of heparin . The switch from enoxaparin to UFH treatment was connected with a significantly higher PF 1 + 2 after 10 and 180 min as well as higher TAT concentration after 180 min of HD . Only during enoxaparin anticoagulated HD 34 % PF 1 + 2 decrease and TAT levels after 180 min of HD was closely associated with heparin dosage . CONCLUSION Single bolus of enoxaparin ensures efficient and convenient anti-thrombotic protection during HD procedure . Enoxaparin mean dose of 0.67 mg/kg , which is generally lower than manufacturer 's instructions , can be recommended for over-dialytic regular use Citrate and nadroparin calcium , a low molecular weight heparin ( LMWH ) , were compared in a r and omized cross-over trial in 21 chronic hemodialysis patients regarding anticoagulation , calcium and magnesium kinetics , biocompatibility , dialysis efficiency , and aluminum contamination . Citrate was infused into the arterial line at a minimum rate of 0.68 mmol/min , combined with a calcium and magnesium-free dialysate and intravenous supplementation of calcium and magnesium at rates of 0.22 and 0.10 mmol/min , respectively . Seven patients with a dialysis session of six hours , received 2/3 of the nadroparin dose predialysis , and 1/3 after 2.5 hours ( divided dose ( DD ) group ) . A single predialysis bolus injection of nadroparin was administered to eight patients not on coumarins [ single dose ( SD ) group ] and to six patients on coumarins [ single dose + coumarins ( SD + C ) group ] , all with a dialysis session of four hours . Nineteen patients received a nadroparin dose of 200 ICU/kg . Two patients with a single dose , one of them on coumarins , received a dose of 150 ICU/kg because of a hematocrit < 0.30 . With citrate systemic whole blood activated clotting time ( ACT ) remained unchanged , indicating efficient regional anticoagulation . After two hours of dialysis with nadroparin , systemic ACT increments , that is , the increase compared to predialysis , of the DD , SD , and SD + C groups were 8.8 + /- 1.5 , 18.7 + /- 4.7 , and 33.3 + /- 6.1 seconds , respectively ( mean + /- SEM ) . Postdialysis ACT increments in these groups were 1.5 + /- 3.4 , 17.7 + /- 6.8 , and 30.3 + /- 8.0 seconds . Two hour increments of systemic activated partial thromboplastin time ( APTT ) of the DD , SD , and SD + C groups during nadroparin were 5.0 + /- 1.2 , 15.1 + /- 2.7 , and 32.2 + /- 5.5 seconds , respectively , and the corresponding postdialysis APTT increments were 2.9 + /- 1.4 , 7.8 + /- 2.4 , and 15.8 + /- 2.6 seconds . Two-hour anti-Xa increments of the DD , SD , and SD + C groups amounted to 0.34 + /- 0.07 , 0.67 + /- 0.07 , and 0.80 + /- 0.08 IU/ml . The respective postdialysis anti-Xa increments were 0.21 + /- 0.06 , 0.58 + /- 0.06 , and 0.71 + /- 0.08 IU/ml ( All ACT , APTT and anti-Xa increments were significant ; P < 0.05 ) , except for the ACT increments and the postdialysis APTT increment of the DD group ) . These increments , together with unchanged prothrombin fragments 1 and 2 ( PTF1 + 2 ) , indicate systemic anticoagulation with nadroparin . The increments of serum calcium and magnesium during citrate were comparable to the increments observed with a dialysate containing 1.5 mmol/liter calcium and 0.75 mmol/liter magnesium used in combination with nadroparin . Ionized calcium increments during citrate were significant after the end of dialysis , while the dialysate containing 1.5 mmol/liter calcium induced significant increments during and postdialysis . No differences were observed between citrate and nadroparin regarding biocompatibility ) , ( expressed as dialysis-induced leukopenia and thrombocytopenia ) , and dialysis efficiency [ measured as dialyzer urea and creatinine clearance , normalized weekly whole body urea clearance ( Kt/Vurea ) and time averaged urea concentration ( TACurea ) ] . The citrate solution , if sterilized in glass bottles , contained 2 to 3 micrograms aluminum per mmol citrate , the nadroparin solution 0.009 microgram per 1,000 ICU . Aluminum contamination of the citrate solution was prevented by sterilizing the solution in polypropylene bottles . In conclusion , citrate anticoagulation is regional and is indicated for hemodialysis patients with an active or recently active bleeding focus . However , the citrate solution should be sterilized in polypropylene containers to prevent aluminum contamination . LMWHs induce systemic anticoagulation during hemodialysis , and this effect is enhanced by concomitant coumarin use and mitigated by a divided LMWH dose regimen . For hemodialysis patients not at risk of bleeding , LMWHs provide a simple anticoagulation regimen Objective . Atherosclerotic cardiovascular diseases caused by traditional and non-traditional risk factors are the most common cause of morbidity and mortality in hemodialysis patients . Recently , much interest has been focused on non-traditional factors , such as oxidative stress , inflammation , and endothelial dysfunction . Hemodialysis patients are not only exposed to oxidative stress but also to inflammation . Although anticoagulants are the most frequently used drugs in hemodialysis patients , their effect upon oxidative stress and inflammation in dialysis patients are still unknown . Methods . Thirty-three hemodialysis patients were r and omized into three groups . Group 1 received st and ard heparin while group 2 received low molecular weight heparin during the dialysis therapy . Group 3 ( control group ) did not receive any anticoagulant agent . Investigators were blinded to the therapy . Serum concentrations of oxidative stress and inflammation markers , including C-reactive protein , tumor necrosis factor alpha , superoxide dismutase , and malondialdehyde , were measured before and after dialysis session . Results . The oxidative stress and inflammation markers were significantly increased in groups 1 and 3 ( p < 0.05 for each ) compared to their baseline values . In contrast , baseline and end-treatment values of the oxidative stress and inflammation markers were comparable in the group 2 ( p > 0.05 ) . Conclusion . These findings indicate that the type of anticoagulants may take a role in the acute effect of hemodialysis upon oxidative stress and inflammation markers . A comparison of the groups revealed that low molecular weight heparin decreased the oxidative stress and inflammation , whereas st and ard heparin increased the oxidative stress and inflammation . Low molecular weight heparin appears to have an additive benefit for hemodialysis patients Low molecular weight ( LMW ) heparin has been compared to st and ard unfractionated ( UF ) heparin in hemodialysis/hemofiltration in a 12 month , r and omized study . Seventy patients with end-stage chronic renal failure starting dialysis treatment were r and omly assigned to one of two groups treated with either LMW or UF heparin . The LMW and UF heparin doses used produced similar plasma anti-FXa levels , and comparable antithrombotic effectiveness was observed in the two groups as reflected in similar incidences of thrombus formation in the extracorporeal circulation : 1.59 % and 1.33 % for LMW and UF heparin , respectively . No bleeding complications were seen with either heparin , but significantly ( P less than 0.05 ) fewer erythrocyte concentrates were needed in the LMW heparin patients . Mean factor VIII activities had risen significantly ( P less than 0.001 ) after 12 months in the UF heparin group , whereas they were unchanged in the LMW heparin group . A significant ( P less than 0.05 ) increase in plasma triglycerides was observed in the UF heparin group which was attributable to six ( 18.8 % ) of the patients in this group . Triglyceride concentrations remained relatively constant in the LMW heparin group . Post-heparin lipolytic activity , and in particular hepatic lipase activity , was not stimulated to the same extent in the LMW heparin-treated patients as compared to the UF heparin group . We conclude that LMW heparin is a suitable alternative to st and ard UF heparin for anticoagulation in hemodialysis/hemofiltration therapy . It may offer potential advantages with regard to a lower requirement for erythrocyte concentrates and less derangement of certain metabolic parameters , such as factor VIII , triglycerides and plasma lipase activity BACKGROUND Low molecular weight heparins ( LMWHs ) and danaparoid are an alternative to unfractionated heparin ( UH ) for anticoagulation during hemodialysis . Few data are available concerning their duration of action and whether drug accumulation occurs with continued use . We performed a prospect i ve r and omized study of the pharmacokinetics of dalteparin and enoxaparin plus danaparoid in 21 hemodialysis patients . METHODS Patients were r and omly assigned to administration of enoxaparin , 40 mg ; dalteparin , 2,500 U ; or danaparoid , 34 U/kg , for 4 weeks . Antifactor Xa levels were measured at the end of weeks 1 and 4 immediately before the injection and at prescribed intervals up to 48 hours postinjection . RESULTS No bleeding or thrombotic episodes occurred during the study . Mean antifactor Xa activities 4 hours postinjection were 0.2 + /- 0.035 ( SEM ) , 0.38 + /- 0.028 , and 0.54 + /- 0.051 U/mL week 1 and 0.26 + /- 0.038 , 0.40 + /- 0.055 , and 0.64 + /- 0.050 U/mL week 4 for dalteparin , enoxaparin , and danaparoid , respectively . Both weeks 1 and 4 , antifactor Xa activity 3 hours postdose was significantly greater for danaparoid sodium compared with enoxaparin and dalteparin . There were no significant differences between antifactor Xa activity week 4 versus week 1 for enoxaparin and dalteparin ; however , danaparoid sodium levels during dialysis were significantly greater after 4 weeks of treatment ( P = 0.0328 , 1 hour ; P = 0.003 , 2 hours ; P = 0.0128 , 3 and 4 hours ) . CONCLUSION Dalteparin and enoxaparin provide adequate anticoagulation for hemodialysis using single bolus injections at relatively low doses . Danaparoid sodium at the current recommended dosage result ed in greater anticoagulation than enoxaparin or dalteparin and may have OBJECTIVE To compare the anticoagulation efficacy and clinical safety of domestically manufactured and imported low-molecular-weight-heparin during hemodialysis . METHODS Sixty patients on hemodialysis were r and omly divided into 2 groups , who received intravascular injections of domestically manufactured or imported low-molecular-weight heparin to prevent coagulation . Active partial thromboplastin time ( aPTT ) , prothrombin time ( PT ) , thrombin time ( TT ) and factor Xa activity were determined during dialysis . RESULTS No incidence of major bleeding was encountered in all of these patients . Similarly low incidences of clotting in extracorporeal circuit were found in either group . No significant differences in aPTT , PT , TT and plasma levels of factor Xa were observed between the two groups . CONCLUSION Low-molecular-weight heparin domestically manufactured is safe and efficient for anticoagulation during hemodialysis as compared with the imported heparin |
1,659 | 28,942,507 | Physical exercise has become a therapy for T2DM , because it improves physical fitness and functional capacity , enhances metabolic control and insulin sensitivity , reduces inflammatory markers and neuropathy symptoms and can increase the regenerative capacity of cutaneous axons , slowing or preventing neuropathy progression .
However , it is not clear to what extent physical exercise can improve HRV in this population .
Weekly frequency might be the most important factor to improve HRV .
These aspects could help to design better programs based in scientific evidence , incorporating HRV as an important variable associated with diabetic neuropathy and mortality | Purpose of Review The aim of the present systematic review is to provide an up-to- date analysis of the research on the effects of exercise programs on heart rate variability ( HRV ) in individuals with type 2 diabetes mellitus ( T2DM ) .
Recent Findings Although HRV is not routinely measured in the management of T2DM , it is an important measure due to its relation with mortality and diabetic neuropathy . | Obesity and type 2 diabetes ( T2D ) are associated with abnormal cardiovascular autonomic function and increased risk for cardiac complications , especially after exercise . Since improvements at rest are not always observed after training , we investigated changes in resting and post-exercise autonomic function in obese women with and without T2D after16-week of walking training . Heart rate ( HR ) variability ( HRV ) and baroreflex sensitivity ( BRS ) were measured at rest and 20 min after a 20 min bout of treadmill exercise at 65 % VO2 peak in obese women with ( n = 8) and without T2D ( n = 12 ) before and after training . HRV was analyzed by frequency-domain [ high- ( HF ) power and low-frequency ( LF ) ] and BRS by the sequence method . Exercise training induced similar significant changes in VO2 peak , resting systolic blood pressure ( SBP ) and post-exercise autonomic function in both groups . Training increased VO2 peak ( 6 % ; P < 0.01 ) and decreased resting SBP ( 8 % ; P < 0.001 ) . Increased post-exercise HR recovery ( 5 % ; P < 0.001 ) , HF power ( 14 % ; P < 0.05 ) , LF power ( 14 % ; P < 0.05 ) and BRS ( 86 % ; P < 0.001 ) were also observed . Resting autonomic function and post-exercise SBP were not altered after training . In conclusion , endurance training reduced blood pressure without changes in HRV and BRS at rest , but training increased HRV and BRS during the recovery of acute endurance exercise indicating an improved post-exercise autonomic modulation of HR , which was similar in obese women with and without T2D Aims /hypothesisGait characteristics and balance are altered in diabetic patients . Little is known about possible treatment strategies . This study evaluates the effect of a specific training programme on gait and balance of diabetic patients . Methods This was a r and omised controlled trial ( n = 71 ) with an intervention ( n = 35 ) and control group ( n = 36 ) . The intervention consisted of physiotherapeutic group training including gait and balance exercises with function-orientated strengthening ( twice weekly over 12 weeks ) . Controls received no treatment . Individuals were allocated to the groups in a central office . Gait , balance , fear of falls , muscle strength and joint mobility were measured at baseline , after intervention and at 6-month follow-up . Results The trial is closed to recruitment and follow-up . After training , the intervention group increased habitual walking speed by 0.149 m/s ( p < 0.001 ) compared with the control group . Patients in the intervention group also significantly improved their balance ( time to walk over a beam , balance index recorded on Biodex balance system ) , their performance-oriented mobility , their degree of concern about falling , their hip and ankle plantar flexor strength , and their hip flexion mobility compared with the control group . After 6 months , all these variables remained significant except for the Biodex sway index and ankle plantar flexor strength . Two patients developed pain in their Achilles tendon : the progression for two related exercises was slowed down . Conclusions /interpretationSpecific training can improve gait speed , balance , muscle strength and joint mobility in diabetic patients . Further studies are needed to explore the influence of these improvements on the number of reported falls , patients ’ physical activity levels and quality of life . Trial registration : Clinical Trials.gov NCT00637546 Funding : This work was supported by the Swiss National Foundation ( SNF ) : Objective : The objective of this study was to eluci date whether the degree of autonomic modulation is associated with the degree of microvascular complications in patients with type 1 diabetes . Methods : A total of 290 type 1 individuals with diabetes were r and omly recruited during normal visits to outpatient clinics at 4 Danish hospitals . The degree of autonomic modulations was quantified by measuring heart rate variability ( HRV ) during passive spectral analysis and active tests ( valsalva ratio [ VT ] , response to st and ing [ RT ] , and deep breathing [ E : I ] ) . To describe possible associations between severity of microvascular complications and measures of autonomic modulation , multivariate analysis was performed . Results : After adjusting for diabetes duration , sex , age , pulse pressure , heart rate , and smoking , autonomic dysfunction remained significantly correlated with severity of retinopathy , nephropathy , and peripheral neuropathy in individuals with type 1 diabetes patients . Conclusions : Autonomic dysfunction is present in early stages of retinopathy , nephropathy , and peripheral neuropathy in patients with type 1 diabetes BACKGROUND Diabetes is the most important cause of peripheral neuropathy ( DPN ) . No definitive treatment for DPN has been established , and very few data on the role of exercise training on DPN have been reported . AIM OF THE STUDY We sought to examine the effects of long-term exercise training on the development of DPN in both Types 1 and 2 diabetic patients . PARTICIPANTS AND METHODS Seventy-eight diabetic patients without signs and symptoms of peripheral DPN were enrolled , r and omized , and subdivided in two groups : 31 diabetic participants [ 15 f , 16 m ; 49+/-15.5 years old ; body mass index ( BMI ) = 27.9+/-4.7 ] , who performed a prescribed and supervised 4 h/week brisk walking on a treadmill at 50 % to 85 % of the heart rate reserve ( exercise group : EXE ) , and a control group of 47 diabetic participants ( CON ; 24 f , 23 m ; 52.9+/-13.4 years old ; BMI = 30.9+/-8.4 ) . Vibration perception threshold ( VPT ) , nerve distal latency ( DL ) , nerve conduction velocity ( NCV ) , and nerve action potential amplitude ( NAPA ) in the lower limbs were measured . RESULTS We found significant differences on Delta ( delta ) in NCV for both peroneal and sural motor nerve between the EXE and CON groups during the study period ( P<.001 , for both ) . The percentage of diabetic patients that developed motor neuropathy and sensory neuropathy during the 4 years of the study was significantly higher in the CON than the EXE group ( 17 % vs. 0.0 % , P<.05 , and 29.8 % vs. 6.45 % , P<.05 , respectively ) . In addition , the percentage of diabetic patients who developed increased VPT ( 25 V ) during the study was significantly higher in the CON than the EXE group ( 21.3 % vs. 12.9 % , P<.05 ) . Change on Hallux VPT from baseline to the end of the study was significantly different between the EXE and CON groups ( P<.05 ) ; no significant change in Malleolus VPT between the two groups occurred . CONCLUSIONS This study suggests , for the first time , that long-term aerobic exercise training can prevent the onset or modify the natural history of DPN Background Low heart rate variability ( HRV ) is associated with a higher risk of death in patients with heart disease and in elderly subjects and with a higher incidence of coronary heart disease ( CHD ) in the general population . Methods and Results We studied the predictive value of HRV for CHD and death from several causes in a population study of 14 672 men and women without CHD , aged 45 to 65 , by using the case-cohort design . At baseline , in 1987 to 1989 , 2-minute rhythm strips were recorded . Time-domain measures of HRV were determined in a r and om sample of 900 subjects , for all subjects with incident CHD ( 395 subjects ) , and for all deaths ( 443 subjects ) that occurred through 1993 . Relative rates of incident CHD and cause-specific death in tertiles of HRV were computed with Poisson regression for the case-cohort design . Subjects with low HRV had an adverse cardiovascular risk profile and an elevated risk of incident CHD and death . The increased risk of death could not be attributed to a specific cause and could not be explained by other risk factors . Conclusions Low HRV was associated with increased risk of CHD and death from several causes . It is hypothesized that low HRV is a marker of less favorable health Heart rate ( HR ) variability has been extensively studied in patients surviving an acute myocardial infa rct ion ( AMI ) . The majority of studies have shown that patients with reduced or abnormal HR variability/turbulence have an increased risk of mortality within few years after an AMI . Various measures of HR dynamics , such as time-domain , spectral , and non-linear measures of HR variability , as well as HR turbulence , have been used in risk stratification of post-AMI patients . The prognostic power of various measures , except of those reflecting rapid R – R interval oscillations , has been almost identical , albeit some non-linear HR variability measures , such as short-term fractal scaling exponent , and HR turbulence , have provided somewhat better prognostic information than the others . Abnormal HR variability predicts both sudden and non-sudden cardiac death after AMI . Because of remodeling of the arrhythmia substrate after AMI , early measurement of HR variability to identify those at high risk should likely be repeated later in order to assess the risk of fatal arrhythmia events . Future r and omized trials using HR variability/turbulence as one of the pre-defined inclusion criteria will show whether routine measurement of HR variability/turbulence will become a routine clinical tool for risk stratification of post-AMI patients BACKGROUND Heart rate variability ( HRV ) reflects autonomic nervous system modulation of cardiac activity . There is a relationship between degrees of physical activity , HRV changes and the risk of cardiovascular disease . AIM To study the effect of a supervised integrated exercise programme on HRV in type 2 diabetes mellitus ( DM ) . METHODS The study group consisted of 48 patients ( 27 males , mean age 62+/-7 years ) with type 2 diabetes , of whom 28 underwent a special exercise programme whereas the remaining 20 did not and served as the control group . The supervised integrated exercise programme was applied for a period of 9 months . Deep breathing time domain HRV ( difference between the shortest and the longest R-R interval over one minute ) was measured at baseline and after 3 , 6 and 9 months . RESULTS A significant improvement in the HRV values was observed with increasing duration of exercise ( 13.03+/-1.08 beats/min at baseline versus 16.5+/-1.11 beats/min at 9 months , p < 0.001 ) whereas HRV decreased in the control group ( 14.85+/-1.15 beats/min at baseline vs. 14.30+/-1.75 at 9 months , p < 0.05 ) . Favourable changes in HRV in the exercise group were gender-dependent and were significant in males ( 12.4+/-1.76 beats/min at baseline vs. 16.18+/-1.91 at 9 months , p < 0.001 ) whereas in females only a trend towards HRV improvement was observed . The HRV changes were also age-dependent and were more pronounced in younger patients than in the elderly . The metabolic parameters of diabetes control ( blood glucose and glycosylated haemoglobin levels ) significantly improved in the exercise group and significantly worsened in the control group . CONCLUSIONS Regular supervised integrated exercise significantly improves HRV in patients with type 2 DM , which may favourably influence their long-term prognosis [ Purpose ] This study evaluated the effects of 12 weeks combined aerobic and resistance exercise on heart rate variability in patients with Type 2 diabetes mellitus . [ Subjects and Methods ] The subjects were 16 female patients with Type 2 diabetes mellitus selected among the participants of a chronic disease management exercise class at C Region Public Health Center in South Korea . Subjects were r and omly assigned to the exercise group ( n=8 ; age , 55.97 ± 7.37 ) or the control group ( n=8 ; age , 57.53 ± 4.63 ) The exercise group performed aerobic and resistance exercises for 60 minutes per day , 3 times per week for 12 weeks . Anthropometric measurements , biochemical markers , physical fitness , and heart rate variability were examined . [ Results ] After 12 weeks of exercise , weight , body fat percentage , waist circumference , blood glucose , insulin resistance , glycated hemoglobin level , systolic blood pressure , and diastolic blood pressure significantly decreased and cardiorespiratory fitness and muscular strength significantly increased in the exercise group . Although heart rate variability measures showed favorable changes with the exercise program , none were significant . [ Conclusion ] Although the exercise program did not show notable changes in heart rate variability in patients with Type 2 diabetes within the timeframe of the study , exercise may contribute to the prevention and control of cardiovascular autonomic neuropathy Autonomic neuropathy in diabetes leads to impaired regulation of blood pressure and heart rate variability ( HRV ) , which is due to a shift in cardiac autonomic balance towards sympathetic dominance . Lower HRV has been considered a predictor of cardiac mortality and morbidity . Deep breathing test is a simple method to measure HRV and it provides a sensitive measure of cardiac autonomic function . The effect of long-term physical activity on HRV in type-2 diabetes mellitus is inconclusive . We aim ed to evaluate the effects of regular physical exercise on HRV with deep breathing in type 2 diabetes ( n = 105 ) . Thirty normotensive diabetic patients and 25 hypertensive diabetic patients underwent physical exercise program for 12 months , and the other 50 patients ( 22 normotensive and 28 hypertensive diabetic patients ) were considered the non-exercised group . Electrocardiogram was recorded during deep breathing and HRV was measured . Regular exercise significantly increased HRV in diabetic patients with and without hypertension . The degree of the increase in HRV was greater in hypertensive diabetic patients ( p < 0.01 ) than in normotensive diabetic patients ( p < 0.05 ) . After exercise , glycosylated hemoglobin levels were decreased in both groups of diabetic patients . Moreover , the hypertensive diabetic patients showed a decrease ( p < 0.05 ) in blood pressure after regular exercise . Thus , regular exercise training increases HRV , suggesting that there is a shift in the cardiac sympathovagal balance in favor of parasympathetic dominance in diabetic patients . Long-term physical training may be an effective means to reverse the autonomic dysregulation seen in type 2 diabetes We evaluated the associations between glycemic therapies and prevalence of diabetic peripheral neuropathy ( DPN ) at baseline among participants in the Bypass Angioplasty Revascularization Investigation 2 Diabetes ( BARI 2D ) trial on medical and revascularization therapies for coronary artery disease ( CAD ) and on insulin-sensitizing vs. insulin-providing treatments for diabetes . A total of 2,368 patients with type 2 diabetes and CAD was evaluated . DPN was defined as clinical examination score > 2 using the Michigan Neuropathy Screening Instrument ( MNSI ) . DPN odds ratios across different groups of glycemic therapy were evaluated by multiple logistic regression adjusted for multiple covariates including age , sex , hemoglobin A1c ( HbA1c ) , and diabetes duration . Fifty-one percent of BARI 2D subjects with valid baseline characteristics and MNSI scores had DPN . After adjusting for all variables , use of insulin was significantly associated with DPN ( OR = 1.57 , 95 % CI : 1.15 - 2.13 ) . Patients on sulfonylurea ( SU ) or combination of SU/metformin (Met)/thiazolidinediones ( TZD ) had marginally higher rates of DPN than the Met/TZD group . This cross-sectional study in a cohort of patients with type 2 diabetes and CAD showed association of insulin use with higher DPN prevalence , independent of disease duration , glycemic control , and other characteristics . The causality between a glycemic control strategy and DPN can not be evaluated in this cross-sectional study , but continued assessment of DPN and r and omized therapies in BARI 2D trial may provide further explanations on the development of DPN BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . Type 2 diabetes is a strong risk factor for coronary heart disease and sudden cardiac death . It is associated with reduced baroreflex sensitivity ( BRS ) and heart rate variability ( HRV ) , which are indicators of increased risk for mortality and morbidity in various patient population s. This study was design ed to assess the effects of exercise training on BRS , HRV , and hemodynamics in patients with type 2 diabetes . Subjects ( 50 men , mean age 53.3 + /- 5.1 years ) with type 2 diabetes were r and omized into either a control group , in which they received conventional treatment only , or an exercise group , in which they received conventional treatment together with heart rate-controlled endurance training twice a week and supervised muscle strength training twice a week for 12 months . Measurements taken at baseline and follow-up included VO(2max ) , st and ard time and frequency domain measures of HRV during 24-h recording , and BRS by the phenylephrine method . Cardiac index , systemic vascular resistance index , stroke index , and pulse wave velocity were measured by whole-body impedance cardiography . Significant improvements in VO(2max ) ( exercise group : + 2.3 ml x kg(-1 ) x min(-1 ) ; P < 0.005 vs. control group ) , muscle strength , and glycemic control ( exercise group : HbA(1c ) -0.9 % ; P < 0.001 vs. control group ) were observed in the exercise group . BRS increased in the exercise group , from 6.8 to 8.6 ms/mmHg , and decreased in the control group , from 7.5 to 6.4 ms/mmHg ( 95 % CI for the difference between 0.05 and 4.36 ms/mmHg ; P < 0.05 ) . No significant changes in the time or frequency domain measures of HRV or in systemic hemodynamics were observed . We concluded that exercise training improves BRS sensitivity in type 2 diabetes subjects in addition to increasing the exercise capacity and muscle strength and improving glucose control . These beneficial effects in reflectory autonomic regulation and glucose control caused by exercise may be associated with improved prognosis of type 2 diabetes patients UNLABELLED Although exercise can significantly reduce the prevalence and severity of diabetic complications , no studies have evaluated the impact of exercise on nerve function in people with diagnosed diabetic peripheral neuropathy ( DPN ) . The purpose of this pilot study was to examine feasibility and effectiveness of a supervised , moderately intense aerobic and resistance exercise program in people with DPN . We hypothesized that the exercise intervention can improve neuropathic symptoms , nerve function , and cutaneous innervation . METHODS A pre-test post-test design was used to assess change in outcome measures following participation in a 10-week aerobic and strengthening exercise program . Seventeen subjects with diagnosed DPN ( 8 males/9 females ; age 58.4±5.98 ; duration of diabetes 12.4±12.2 years ) completed the study . Outcome measures included pain measures ( visual analog scale ) , Michigan Neuropathy Screening Instrument ( MNSI ) question naire of neuropathic symptoms , nerve function measures , and intraepidermal nerve fiber ( IENF ) density and branching in distal and proximal lower extremity skin biopsies . RESULTS Significant reductions in pain ( -18.1±35.5 mm on a 100 mm scale , P=.05 ) , neuropathic symptoms ( -1.24±1.8 on MNSI , P=.01 ) , and increased intraepidermal nerve fiber branching ( + 0.11±0.15 branch nodes/fiber , P=.008 ) from a proximal skin biopsy were noted following the intervention . CONCLUSIONS This is the first study to describe improvements in neuropathic and cutaneous nerve fiber branching following supervised exercise in people with diabetic peripheral neuropathy . These findings are particularly promising given the short duration of the intervention , but need to be vali date d by comparison with a control group in future studies OBJECTIVE Autonomic dysfunction may contribute to the etiology and exercise intolerance of sub clinical diabetic heart disease . This study sought the efficacy of exercise training for improvement of peak oxygen uptake ( VO₂(peak ) ) and cardiac autonomic function in type 2 diabetic patients with non-ischemic sub clinical left-ventricular ( LV ) dysfunction . MATERIAL S/ METHODS Forty-nine type 2 diabetic patients with early diastolic tissue Doppler velocity > 1 st and ard deviation below the age-based mean entered an exercise intervention ( n=24 ) or usual care ( n=25 ) for 6-months ( controlled , pre-/post- design ) . Co- primary endpoints were treadmill VO₂(peak ) and 5-min heart-rate variability ( by the coefficient of variation of normal RR intervals [ CVNN ] ) . Autonomic function was additionally assessed by resting heart-rate ( for sympathovagal balance estimation ) , baroreflex sensitivity , cardiac reflexes , and exercise/recovery heart-rate profiles . Echocardiography was performed for LV function ( systolic/diastolic tissue velocities , myocardial deformation ) and myocardial fibrosis ( calibrated integrated backscatter ) . RESULTS VO₂(peak ) increased by 11 % during the exercise intervention ( p=0.001 vs. -1 % in controls ) , but CVNN did not change ( p=0.23 ) . Reduction of resting heart-rate in the intervention group ( p<0.05 ) was associated with an improvement in the secondary endpoint of heart-rate variability total spectral power ( p<0.05 ) . However , baroreflex sensitivity , cardiac reflexes , and exercise/recovery heart-rate profiles showed no significant benefit . No effects on LV function were observed despite favorable reduction of calibrated integrated backscatter in the intervention group ( p<0.05 ) . CONCLUSIONS The exercise intolerance of sub clinical diabetic heart disease was amenable to improvement by exercise training . Despite a reduction in resting heart-rate and potential attenuation of myocardial fibrosis , no other cardiac autonomic or LV functional adaptations were detected Heart rate variability ( HRV ) and haemorheology adaptations to 12 wk of varied-dose treadmill walking were investigated in women aged 65 - 74 yr with type 2 diabetes . Subjects were r and omly allocated into two groups where exercise frequency and session duration were manipulated ( Group 1 : 2 × 60 min·wk(-1 ) or Group 2 : 4 × 30 min·wk(-1 ) ) , but intensity and accumulated weekly duration of exercise were consistent between groups ( 100 % gas-exchange threshold ; 120 min·wk(-1 ) ) . Twelve weeks of exercise training significantly improved peak oxygen uptake , time to exhaustion , and gas-exchange threshold ( p < 0.05 ) , independent of exercise group . Exercise training did not significantly change glycaemic control or body mass . Red blood cell ( RBC ) aggregation and RBC deformability significantly decreased ( p < 0.05 ) for both groups . No change in HRV was observed for Group 1 , whereas several key indicators of HRV were significantly improved in Group 2 ( p < 0.05 ) . The present study was the first to report decreased RBC aggregation following an exercise-only intervention and that exercise training improved RBC aggregation without a concomitant improvement in glycaemic control . The accumulated weekly exercise duration may be the most important training component for the prescription of exercise in older women with type 2 diabetes |
1,660 | 21,901,694 | Reminder packing may represent a simple method for improving adherence for patients with selected conditions . | BACKGROUND Current methods of improving medication adherence for health problems are mostly complex , labour-intensive , and not reliably effective .
Medication ' reminder packaging ' , which incorporates a date or time for a medication to be taken in the packaging , can act as a reminder to improve adherence .
This review of reminder packaging is an up date of our 2006 Cochrane review .
OBJECTIVES The objective of this review was to determine the effects of reminder packaging aids for self-administered medication/s taken for at least one month , on adherence and other outcomes . | Objective The goal of this study was to evaluate clinical ly the acceptability of the IDAS II ( Intelligent Drug Administration System ) , a new electronic device that enables drug adherence monitoring . Methods IDAS II was compared to another electronic monitor , the Medication Event Monitoring System ( MEMS ) in a r and omised two-way cross-over study involving 24 hypertensive patients treated with irbesartan . Patients used each device for 2 months . The main parameter of evaluation was the patients ’ opinion on both devices . Rates of adherence and blood pressure were also assessed . Results Most patients considered both devices to be reliable reminders ( IDAS II : 75%;MEMS : 84 % , p = ns ) . Ten patients ( 42 % ) preferred the MEMS , while 11 ( 46 % ) preferred the IDAS II ; three ( 12 % ) expressed no preference . Patients found the MEMS device easier to use than the IDAS device ( p < 0.001 ) but appreciated the IDAS blister packs better than the MEMS bulk packaging ( p < 0.01 ) . Over the 4-month period , the median “ taking adherence ” was excellent ( 99.2 % ) and comparable with both devices . However , the regularity of drug intake timing was higher with the IDAS II ( p < 0.01 ) . Conclusion IDAS II , a new electronic device enabling drug adherence monitoring without reconditioning of the drugs appears to be a well-accepted device . Overall , practicability and acceptability of the IDAS II and the MEMS device were similar . Thus , IDAS II could be a useful tool for the management of long-term therapies OBJECTIVE To examine the extent to which district health teams could reduce the burden of malaria , a continuing major cause of mortality and morbidity , in a situation where severe re source constraints existed and integrated care was provided . METHODS Antimalarial drugs were prepackaged into unit doses in an attempt to improve compliance with full courses of chemotherapy . FINDINGS Compliance improved by approximately 20 % in both adults and children . There were 50 % reductions in cost to patients , waiting time at dispensaries and drug wastage at facilities . The intervention , which tended to improve both case and drug management at facilities , was well accepted by health staff and did not involve them in additional working time . CONCLUSION The prepackaging of antimalarials at the district level offers the prospect of improved compliance and a reduction in the spread of resistance Outpatient medication adherence is a major problem , especially for patients repeatedly hospitalized for psychiatric disorders . This study included 39 such patients who were receiving case management services from a community mental health center . Patients were matched and r and omly assigned to receive in a single session either ( 1 ) information regarding medication and its benefits , ( 2 ) guidelines for assuring adherence which encompassed all phases related to pill-taking including filling prescriptions , use of a pill container , transportation , self-reminders , doctor 's appointments and so forth , or ( 3 ) the same guidelines as ( 2 ) above but given in the presence of a family member who was enlisted in support . The results showed that adherence increased to about 94 % after the guidelines were given for both the individual and family guideline procedure , whereas adherence remained unchanged at 73 % after the medication information procedure . These results suggest a practical means for assuring a high level of medication adherence for patients with psychiatric disorders We investigated the impact of pre-packaging antimalarial drugs and counselling on compliance with treatment of malaria at the Adult Outpatient Department of Port Moresby General Hospital . Adult patients who were prescribed st and ard antimalarial drugs following clinical and microscopic diagnosis of malaria were r and omly assigned to one of three groups : an intervention group , where pre-packaging and counselling instructions were applied ; control group A , with counselling but no pre-packaging ; and control group B , with neither counselling nor pre-packaging . Patients were interviewed on two occasions , day 1 of treatment and day 4 post treatment . Of a total of 436 patients , 322 patients ( 179 males and 143 females ) completed the study . Our data indicate an increase of 18 % in compliance with treatment in the intervention group and 16 % in control group A , when compared with control group B. While compliance with treatment was gender independent , the language spoken and used for giving instructions and counselling may have influenced patients ' behaviour on prescribed medication . The results of our study indicate that a simple pre-packaging system and proper counselling could improve compliance with antimalarial drug treatment . As an additional beneficial observation , pre-packaging is likely to eliminate errors and possible contamination of the products during dispensing Abstract Objective To determine whether home based medication review by pharmacists affects hospital readmission rates among older people . Design R and omised controlled trial . Setting Home based medication review after discharge from acute or community hospitals in Norfolk and Suffolk . Participants 872 patients aged over 80 recruited during an emergency admission ( any cause ) if returning to own home or warden controlled accommodation and taking two or more drugs daily on discharge . Intervention Two home visits by a pharmacist within two weeks and eight weeks of discharge to educate patients and carers about their drugs , remove out of date drugs , inform general practitioners of drug reactions or interactions , and inform the local pharmacist if a compliance aid is needed . Control arm received usual care . Main outcome measure Total emergency readmissions to hospital at six months . Secondary outcomes included death and quality of life measured with the EQ-5D . Results By six months 178 readmissions had occurred in the control group and 234 in the intervention group ( rate ratio = 1.30 , 95 % confidence interval 1.07 to 1.58 ; P = 0.009 , Poisson model ) . 49 deaths occurred in the intervention group compared with 63 in the control group ( hazard ratio = 0.75 , 0.52 to 1.10 ; P = 0.14 ) . EQ-5D scores decreased ( worsened ) by a mean of 0.14 in the control group and 0.13 in the intervention group ( difference = 0.01 , -0.05 to 0.06 ; P = 0.84 , t test ) . Conclusions The intervention was associated with a significantly higher rate of hospital admissions and did not significantly improve quality of life or reduce deaths . Further research is needed to explain this counterintuitive finding and to identify more effective methods of medication review BACKGROUND type 2 diabetes mellitus continues to increase in prevalence worldwide . Many factors have been cited as contributing to compliance , such as family and social support , education , number of tablets per dose , frequency of administration and health care provider communication . Toward these goals , the present study was developed to measure the effect offactors on glycemic control such as diabetes education by pharmacists , a diabetes disease booklet and special medication containers . MATERIAL AND METHOD A total of 360 volunteers with type 2 DM patients were recruited , participants were simple r and omized to control 180 and intervention 180 patients . Which intervention categorized to 4 groups ; all intervention groups received diabetes drug counseling by a pharmacist , one group received plus a diabetes booklet , one received plus special medical containers and the last group received all of them . The interventions were done at the 1st time of visit . Both the control and intervention groups were monitored for fasting plasma glucose and HbA1c at 0 , 3 , 6 months and glycemic level in both groups was compared . RESULTS After 3 months , mean fasting plasma glucose and HbA1c decreased wiih the intervention group vs. control group ( 152.36 + /- 39.73 to 131.52 + /- 35.22 mg% ) and ( 150.16 + /- 41.78 to 153.98 + /- 47.95 mg% ) respectively ; ( p < 0.001 ) . HbA1c level 8.16 + /- 1.44 to 7.72 + /- 1.26 vs 8.01 + /- 1.51 to 8.38 + /- 1.46 respectively ; ( p < 0.001 ) . After 6 months , mean fasting plasma glucose and HbA1c decreased with the intervention group vs. control group ( 152.36 + /- 39.73 to 145.20 + /- 46.07 mg% ) and ( 150.16 + /- 41.78 to 159.16 + /- 54.90 mg% ) respectively ; ( p < 0.013 ) . HbA1c level 8.16 + /- 1.44 to 7.91 + /- 1.27 vs. 8.01 + /- 1.51 to 8.80 + /- 1.36 respectively ; ( p < 0.001 ) . The most favorable glycemic outcome was the group that received all of the interventions ; mean FPG was reduced from 147.46 + /- 36.07 to 125.38 + /- 31.12 mg% ( p < 0.000 ) in 1nd visit ( 3 months later ) and still reducing effect on the 2nd visit ( 6 month later ) mean FPG from 147.46 + /- 36.07 to 130.21 + /- 33.96 mg% ( p < 0.016 ) also the same way in HbA 1c level . The group that received only drug counseling by pharmacist had no significant reduction in FPG and HbA1c . ( p > 0.05 ) . CONCLUSION Drug counseling by a pharmacist has little beneficial effect on diabetes management outcome compared to the diabetes booklet and special drug container . To improve glycemic control of type 2 DM is to integrate self-management in daily life , wide a variety of education , drug taken behavior and health care provider available communication produce improvement in patient management and is somewhat better when used in combination CONTEXT Rising costs of medications and inequities in access have sparked calls for drug policy reform in the United States and Canada . Control of drug expenditures by prescription cost-sharing for elderly persons and poor persons is a contentious issue because little is known about the health impact in these subgroups . OBJECTIVES To determine ( 1 ) the impact of introducing prescription drug cost-sharing on use of essential and less essential drugs among elderly persons and welfare recipients and ( 2 ) rates of emergency department ( ED ) visits and serious adverse events associated with reductions in drug use before and after policy implementation . DESIGN AND SETTING Interrupted time-series analysis of data from 32 months before and 17 months after introduction of a prescription coinsurance and deductible cost-sharing policy in Quebec in 1996 . Separate 10-month prepolicy control and postpolicy cohort studies were conducted to estimate the impact of the drug reform on adverse events . PARTICIPANTS A r and om sample of 93 950 elderly persons and 55 333 adult welfare medication recipients . MAIN OUTCOME MEASURES Mean daily number of essential and less essential drugs used per month , ED visits , and serious adverse events ( hospitalization , nursing home admission , and mortality ) before and after policy introduction . RESULTS After cost-sharing was introduced , use of essential drugs decreased by 9.12 % ( 95 % confidence interval [ CI ] , 8.7%-9.6 % ) in elderly persons and by 14.42 % ( 95 % CI , 13.3%-15.6 % ) in welfare recipients ; use of less essential drugs decreased by 15.14 % ( 95 % CI , 14.4%-15.9 % ) and 22.39 % ( 95 % CI , 20.9%-23.9 % ) , respectively . The rate ( per 10 000 person-months ) of serious adverse events associated with reductions in use of essential drugs increased from 5.8 in the prepolicy control cohort to 12.6 in the postpolicy cohort in elderly persons ( a net increase of 6.8 [ 95 % CI , 5.6 - 8.0 ] ) and from 14.7 to 27.6 in welfare recipients ( a net increase of 12.9 [ 95 % CI , 10.2 - 15.5 ] ) . Emergency department visit rates related to reductions in the use of essential drugs also increased by 14.2 ( 95 % CI , 8.5 - 19.9 ) per 10 000 person-months in elderly persons ( prepolicy control cohort , 32.9 ; postpolicy cohort , 47.1 ) and by 54.2 ( 95 % CI , 33.5 - 74.8 ) among welfare recipients ( prepolicy control cohort , 69.6 ; postpolicy cohort , 123.8 ) . These increases were primarily due to an increase in the proportion of recipients who reduced their use of essential drugs . Reductions in the use of less essential drugs were not associated with an increase in risk of adverse events or ED visits . CONCLUSIONS In our study , increased cost-sharing for prescription drugs in elderly persons and welfare recipients was followed by reductions in use of essential drugs and a higher rate of serious adverse events and ED visits associated with these reductions OBJECTIVE To examine the relationship between adherence to a medical regimen and mortality following a myocardial infa rct ion in women . DESIGN Analysis of the female cohort entered into a r and omized double-blind multicenter trial . SETTING National Heart , Lung , and Blood Institute beta-Blocker Heart Attack Trial . PARTICIPANTS The 602 women , aged 30 to 69 years , enrolled in the beta-Blocker Heart Attack Trial . INTERVENTION R and om assignment to propranolol hydrochloride or placebo 5 to 21 days following a myocardial infa rct ion . MEASUREMENTS Adherence for each patient was calculated as the mean of all quarterly adherence estimates during the course of the trial ( median follow-up , 26 months ) . Adherence was classified as good ( taking > or = 75 % of medication ) or poor ( taking < 75 % of medication ) . The end point was death from all causes occurring at any time during the trial , adjusted for treatment category and other clinical and sociodemographic features . RESULTS Adherence data were available on 505 women , of whom 32 ( 6.3 % ) died . Death occurred in 13.6 % of poor adherers compared with 5.6 % of good adherers ( relative risk , 2.4 ; 95 % confidence interval , 1.1 to 5.6 ) . The effect of adherence on mortality remained undiminished after adjustment for treatment category ( propranolol or placebo ) , age , severity of myocardial infa rct ion , congestive heart failure , smoking history , marital status , educational level , and race ( adjusted relative risk of death for poor adherers , 2.5 to 3.0 ; P < or = .02 ) . CONCLUSIONS The independent effect of adherence on mortality following a myocardial infa rct ion in women is clinical ly substantial , statistically significant , and similar in magnitude to that reported earlier for men Background Adherence with medication taking is a major barrier to physiologic control in diabetes and many strategies for improving adherence are in use . We sought to describe the use of mnemonic devices and other adherence aids by adults with diabetes and to investigate their association with control of hyperglycemia , hyperlipidemia and hypertension . Methods Cross sectional survey of diabetic adults r and omly selected from Primary Care practice s in the Vermont Diabetes Information System . We used linear regression to examine the associations between the use of various aids and physiologic control among subjects who used oral agents for hyperglycemia , hypercholesterolemia , and hypertension . Results 289 subjects ( mean age 65.4 years ; 51 % female ) used medications for all three conditions . Adherence aids were reported by 80 % . The most popular were day-of-the-week pill boxes ( 50 % ) , putting the pills in a special place ( 41 % ) , and associating pill taking with a daily event such as a meal , TV show , or bedtime ( 11 % ) . After adjusting for age , sex , marital status , income , and education , those who used a special place had better glycemic control ( A1C -0.36 % ; P = .04 ) and systolic blood pressure ( -5.9 mm Hg ; P = .05 ) than those who used no aids . Those who used a daily event had better A1C ( -0.56 % ; P = .01 ) than patients who used no aids . Conclusion Although adherence aids are in common use among adults with diabetes , there is little evidence that they are efficacious . In this study , we found a few statistically significant associations with adherence aids and better diabetes control . However , these findings could be attributed to multiple comparisons or unmeasured confounders . Until more rigorous evaluations are available , it seems reasonable to recommend keeping medicines in a special place for diabetic adults prescribed multiple medications An estimated 20 million Americans suffer from diabetes . Patients with non-insulin-dependent diabetes mellitus ( NIDDM ) comprise approximately 90 % of the diabetic population . An estimated 10 - 30 % of patients with NIDDM withdraw from their prescribed regimen within 1 year of diagnosis , and of the remainder , nearly 20 % administer insufficient medication to facilitate an adequate reduction in blood glucose . A r and omized trial was undertaken to discern the effect of pharmacy-based value-added utilities on prescription-refill compliance with sulfonylurea therapy and health service utilization . The subjects were 258 Medicaid beneficiaries from the state of South Carolina , previously untreated for NIDDM , prescribed 5 mg of the second-generation sulfonylurea glyburide twice daily , and monitored with regard to prescription-refill compliance and health service utilization for 1 year . Subjects provided informed consent and were r and omly assigned to one of four experimental groups : ( i ) the control cohort received st and ard pharmaceutical care with each dispensing of glyburide ; ( ii ) the second cohort received st and ard pharmaceutical care and was mailed a medication-refill reminder 10 days prior to each sequential refill date ; ( iii ) the third cohort received st and ard pharmaceutical care and was provided unit-of-use packaging with each prescription-refill request ; ( iv ) the fourth cohort received st and ard pharmaceutical care , mailed medication-refill reminders , and unit-of-use packaging . Analysis of variance ( ANOVA ) procedures revealed that patients receiving mailed prescription-refill reminders , unit-of-use packaging , or a combination of both interventions achieved a significant ( P < or = 0.05 ) increase in the Medication Possession Ratio ( MPR ) for sulfonylurea therapy relative to controls . ( ABSTRACT TRUNCATED AT 250 WORDS A multifactorial health-education program design ed to enhance compliance with a once-daily regimen of atenolol was evaluated among 453 patients enrolled in health maintenance organizations ( HMOs ) . The initiation of the 180-day study period was used to classify patients as either new or existing cases of hypertension . In turn , patients in these two categories were r and omly assigned to a control or an experimental group . Patients assigned to the experimental groups received an enrollment kit upon exercising their initial prescription ( new patients ) or their first refill request ( existing patients ) . The kit contained : a 30-day supply of atenolol ; an educational newsletter about hypertension ; information on nutrition and life-style changes ; and an explanation of the intent and content of the program . Before the next scheduled prescription-refill date , each patient was contacted by telephone to inquire about his or her experience with the therapy and to stress the importance of adherence to the regimen . Each month thereafter , the newsletter and an enclosed prescription-refill reminder were mailed to each patient . The medication possession ratio , defined as the number of days ' supply of atenolol obtained by a patient during the 180-day study period , was significantly ( P less than or equal to 0.001 ) enhanced for the new and existing experimental groups relative to the control groups . Multiple regression analyses revealed that enrollment in the health-education program increased the number of days ' supply of atenolol obtained by existing patients by 27 ( P less than or equal to 0.001 ) , and by new patients by 40 ( P less than or equal to 0.001 ) PURPOSE To investigate the impact of an intervention program to improve adherence with topical , once daily therapy for glaucoma . DESIGN R and omized controlled clinical trial . PARTICIPANTS Sixty-six patients with glaucoma being treated with a prostagl and in analog in 1 or both eyes at the Scheie Eye Institute or Wilmer Eye Institute between November 2006 and June 2007 . METHODS In an observational study , participants who took 75 % or fewer doses ( as measured using the travoprost Dosing Aid [ DA ] ) during an initial 3-month period were r and omized into 2 groups . The intervention group watched an educational video , review ed current barriers to drop-taking and possible solutions with a study coordinator , received regular phone call reminders , and had audible and visible reminders activated on their DA devices . The control group was told to take drops as prescribed and received no additional intervention . MAIN OUTCOME MEASURES Change in drop use adherence as determined by the DA device . RESULTS In the 3-month observation period before r and omization , intervention group patients had used a mean of 54+/-17 % of scheduled doses , and this increased to 73+/-22 % during the following 3-month period ( P<0.001 , n = 35 ) . The control mean adherence rate of 46+/-23 % at baseline was statistically unchanged during the follow-up observation period ( 51+/-30 % , P = 0.16 , n = 31 ) . In a multivariate analysis , intervention , baseline compliance rate of < 50 % , and white ethnicity were predictors of improved adherence during the 3 months of intervention . The intraocular pressure ( IOP ) of the intervention and control groups did not change between months 3 and 6 after intervention ( P = 0.96 , 0.34 , respectively ) , and there was no correlation of IOP change with adherence rate change between both groups ( Pearson correlation r = 0.06 , P = 0.51 ) . CONCLUSIONS A multifaceted intervention significantly increased adherence with glaucoma medications . Those with improved adherence were in the intervention group , had very low adherence rates at baseline , and were white . IOP did not correlate with adherence . Further research is needed to determine which components of this intervention were most effective A study conducted in 1994 showed that the use of blister packs containing antimalarial drugs significantly increased patients ' compliance , compared with traditional means of dispensing drugs in a paper envelope . The present study assessed patients ' compliance and compared the difference between 3-day chloroquine and 8-day primaquine courses of treatment for vivax malaria . The level of real compliance was determined by making the drugs with phenobarbital , and measuring its level in the blood following treatment . The results show that blister packaging significantly improved patients ' compliance ( p < 0.001 ) over traditional means of dispensing antimalarial drugs ; there was no difference in treatment compliance between 3-day and 8-day courses when the drugs were in blister packs . However , with ordinary packaging the treatment compliance rate for an 8-day course was significantly less than for a 3-day course ( P < 0.05 ) OBJECTIVE To compare compliance in type 2 diabetic patients treated with glimepiride once daily or glibenclamide twice to three times daily . METHODS Poorly controlled type 2 diabetic patients aged 35 - 65 years were r and omized to glimepiride 1 mg once daily or to glibenclamide 1.25 mg twice daily . During initial titration , doses ranged from 1 to 6 mg once daily ( glimepiride ) and from 1.25 mg twice daily to 5 mg 3 times daily ( glibenclamide ) to achieve fasting blood glucose < 126 mg/dL. The final titration phase doses were continued during the maintenance phase . Both treatments were packed in electronic pill-boxes fitted with a microprocessor to record date s and times of each opening . Compliance was assessed in terms of mean daily compliance ( MDC ) and the ratio of days with adequate compliance ( DAC ) . Glycemic control was assessed in terms of the adjusted mean final HbA1c , and the incidence of hypoglycemia . Patient satisfaction was evaluated using the Diabetes Treatment Satisfaction Question naire . RESULTS Compliance over the whole study was generally good , but the MDC was significantly better with glimepiride ( 87+/-16 % ) than with glibenclamide ( 80+/-17%;P < 0.0001 ) . The ratios of DAC for glimepiride and glibenclamide were 87+/-16 % and 67+/-24 % respectively ( P < 0.0001 ) . The adjusted final HbA1c , and the incidence of hypoglycemia were similar in the two groups . Treatment satisfaction on the DTSQc was greater with glimepiride than with glibenclamide ( P = 0.0034 ) . CONCLUSIONS Patient compliance and treatment satisfaction with once-daily glimepiride were significantly better than with glibenclamide 2 to 3 times daily The purpose of this paper is to describe electronic monitoring device ( EMD ) ( e.g. , MEMS caps ) use among HIV-infected adults enrolled in a r and omized clinical trial and to make explicit some of the benefits and caveats of using electronic monitoring device technology . This is a descriptive , exploratory study of EMD use among 128 HIV-infected adults treated with at least three antiretroviral agents . Thirty-six percent of the sample admitted that they did not use the EMD consistently . Forty-one percent of the subjects reported taking out more than one dose at a time and 26 % reported opening the EMD but not taking the medication . Special subject-related issues accounted for only a small percentage of all reported problems with EMD use ( e.g. , transient housing , incarceration , substance abuse relapse and drug treatment ) . Results of this study suggest that EMDs may underestimate antiretroviral adherence among HIV-infected adults . Recommendations for improving EMD data quality are presented SUMMARY Measurement of patient compliance is essential if management of low compliance is to be performed efficiently . We assessed the ralue of several easily obtained clinical assessment s compared to quantitative pill counts among 134 newly treated hypertensive male steelworkers during the first 6 months of their treatment with antihypertensJve medication . Patient 's self-reports obtained on structured interview correlated best with pill count compliance ( r = 0.74 , p < 0.0001 ) . Patients overestimated their compliance by an average of 17 % but 90 % of those who admitted to being noocompliant were found so . Qualitative urinary chlorthalidone and hydrochlorothiazide levels and changes in serum potassium , uric acid , and blood pressure also correlated with pill count compliance but were less accurate than interviews . Assessment of the patient's"health beliefs " and a variety of sociodemographic and health traits and perceptions did not provide useful information on compliance . Interviewing the patient is a simple and useful approach in assessing compliance with antihypertensive therapy Background . Patients cite " forgetting " as a reason for nonadherence to highly active antiretroviral therapy ( HAART ) . We measured the effect of a memory-prompting device on adherence to HAART in memory-intact and memory-impaired human immunodeficiency virus (HIV)-infected subjects . Methods . The study was a prospect i ve , r and omized , controlled trial involving 64 HIV-infected adults . The intervention was the Disease Management Assistance System ( DMAS ) device , combined with monthly adherence counseling . Control subjects received only adherence counseling . The DMAS was programmed with HAART regimen data to provide verbal reminders at dosing times . Adherence was measured for 24 weeks using electronic drug exposure monitor ( eDEM ) caps . Results . A total of 58 subjects completed the 24-week study period ; 28 were HAART naive ( 12 DMAS users and 16 control subjects ) . Mean adherence scores did not differ significantly between DMAS users ( 80 % ) and control subjects ( 65 % ) . Post hoc analysis of 31 memory-impaired subjects ( 14 DMAS users and 17 control subjects ) revealed significantly higher adherence rates among DMAS users ( 77 % ) , compared with control subjects ( 57 % ) ( P=.001 ) . However , analysis of memory-intact subjects showed that adherence was not significantly improved for DMAS users ( 83 % ) , compared with control subjects ( 77 % ) ( P=.25 ) . At week twelve , 38 % of the DMAS users and 14 % of the control subjects had an undetectable plasma HIV RNA load ( P=.014 ) , and at week 24 , the plasma HIV RNA load was undetectable for 34 % of the DMAS users and 38 % of the control subjects ( P=.49 ) . CD4(+ ) cell counts did not differ between the study arms . Virological and immunological responses were not related to DMAS use in memory-impaired subjects . Conclusion . The DMAS prompting device improved adherence for memory-impaired subjects but not for memory-intact subjects OBJECTIVES To determine whether an enhanced compliance program ( ECP ) improves patient compliance with bismuth subsalicylate , metronidazole , and tetracycline hydrochloride ( BMT ) triple therapy for the treatment of Helicobacter pylori infection and to identify factors that affect compliance with therapy . DESIGN A r and omized controlled trial conducted in 4 staff-model health centers of a health maintenance organization in Massachusetts . PATIENTS AND METHODS A total of 125 patients 18 years of age or older with peptic ulcer disease or dyspepsia whose clinicians prescribed BMT triple therapy for 14 days were r and omized to a control group or to the ECP group . The ECP group received medication counseling ( written and oral ) from a pharmacist , along with a medication calendar and a minipillbox , as well as a follow-up telephone call after initiation of therapy . Compliance was assessed by a pill count , and factors affecting adherence to the regimen were identified by patients ' reports . RESULTS There was no statistically significant difference between the 2 groups in the number of patients taking more than 60 % of the medications ( 89 % of the control group vs 95 % of the ECP group ; P>.30 ) . However , there was a statistically significant difference in the number of patients taking more than 90 % of the medications ( 67 % of the control group vs 89 % of the ECP group ; P<.01 ) . An intention-to-treat analysis confirmed these results . The most frequently reported adverse effect was gastrointestinal intolerance . Other factors reported to affect compliance included the frequency of dosing and the number of pills . CONCLUSIONS These findings suggest that although adverse effects were common , most patients were able to complete 60 % or more of the 2-week regimen . An ECP further improved the percentage of medications taken Background Low back pain ( LBP ) is a common and costly problem . Initiatives design ed to assist practitioner and patient decisions about appropriate healthcare for LBP include printed evidence -based clinical guidelines . The three professional groups of chiropractic , osteopathy and musculoskeletal physiotherapy in the UK share common ground with their approaches to managing LBP and are amongst those targeted by LBP guidelines . Even so , many seem unaware that such guidelines exist . Furthermore , the behaviour of at least some of these practitioners differs from that recommended in these guidelines .Few r and omised controlled trials evaluating printed information as an intervention to change practitioner behaviour have utilised a no-intervention control . All these trials have used a cluster design and most have method ological flaws . None specifically focus upon practitioner behaviour towards LBP patients . Studies that have investigated other strategies to change practitioner behaviour with LBP patients have produced conflicting results . Although numerous LBP guidelines have been developed worldwide , there is a paucity of data on whether their dissemination actually changes practitioner behaviour . Primarily because of its low unit cost , sending printed information to large numbers of practitioners is an attractive dissemination and implementation strategy . The effect size of such a strategy , at an individual practitioner level , is likely to be small . However , if large numbers of practitioners are targeted , this strategy might achieve meaningful changes at a population level . Methods The primary aim of this prospect i ve , pragmatic r and omised controlled trial is to test the short-term effectiveness ( six-months following intervention ) of a directly-posted information package on the reported clinical behaviour ( primary outcome ) , attitudes and beliefs of UK chiropractors , osteopaths and musculoskeletal physiotherapists . We sought to r and omly allocate a combined sample of 1,800 consenting practitioners to receive either the information package ( intervention arm ) or no information above that gained during normal practice ( control arm ) . We collected question naire data at baseline and six-months post-intervention . The analysis of the primary outcome will assess between-arm differences of proportions of responses to questions on recommendations about activity , work and bed-rest , that fall within categories previously defined by an expert consensus exercise as either ' guideline -consistent ' and ' guideline -inconsistent ' This article reports a r and omized controlled trial design ed to test the effects of special packaging of antihypertensive medication on compliance and blood pressure control . One hundred eighty subjects who had exhibited elevated blood pressure greater than 90 mmHg in the two years prior to the study were recruited from patients receiving care at a community hospital-based family medicine practice . After completing preenrollment interviews and blood pressure measurements , subjects were r and omly assigned to receive their antihypertensive medications either in the usual vials or in special unit dose-reminder packaging . Follow-up interviews , pill counts , and blood pressure measurements were performed at three-month intervals . There were no statistically significant differences between the control and experimental groups with regard to age , sex , race , employment , education , marital status , insurance coverage , or blood pressure regimens . Prior to the intervention , the experimental group had slightly lower diastolic blood pressure and reported better compliance than the control group . Analyses performed on 165 subjects completing the first follow-up visit revealed no significant improvements in blood pressure control or compliance for patients receiving special medication packaging . While some patients found it easy to remember to take pills packaged using this format , they also found the packages somewhat more difficult and inconvenient to use . In contrast to previously reported work , this study did not demonstrate any significant improvement in compliance with special packaging of antihypertensive medications This paper describes a study in which 70 elderly patients were assessed for risk factors in their medication regimen . They were separated into three study groups , including two levels of teaching intervention focused on the home medication administration system , and a control group . The intervention utilizing a follow-up telephone call demonstrated a significant change in risk-related behaviours such as verbalization of the regimen , congruence between instructions and usage of medications , and taking of medicines not currently prescribed or over-the-counter OBJECTIVE : The aim of this study was to compare cure rates of Helicobacter pylori ( H. pylori ) infection , compliance , and side effects in patients given 10 days of omeprazole 20 mg b.d . , amoxycillin 500 mg t.d.s . , and metronidazole 400 mg t.d.s . ( OAM ) or 10 days OAM plus compliance enhancing measures . METHODS : A total of 119 H. pylori-positive patients were prospect ively r and omized to receive either 10 days OAM or 10 days OAM plus compliance enhancing measures ( medication in a dose dispensing unit , medication chart , an information sheet about H. pylori treatment , and phone call 2 days after starting therapy ) . H. pylori eradication was assessed by 13C-UBT at least 4 wk after cessation of therapy , compliance by phone interview on the last day of therapy and returned pill count , and side effects by phone interview and returned side effects form . RESULTS : In 113 patients attending 13C-UBT H. pylori was eradicated in 51 of 57 patients ( 89.5 % ) after 10 days OAM and in 48 of 56 ( 85.7 % ) after 10 days OAM plus compliance enhancing measures ( p= 0.54 ) . In both groups 97 % of medications were taken . Side effects were common ( 82 % of patients ) . Both side effects ( p= 0.001 ) and ulcer versus nonulcer at endoscopy ( p= 0.016 ) were independent predictors of treatment failure ; side effects also predicted noncompliance ( p= 0.02 ) . CONCLUSIONS : Ten days of OAM was effective for H. pylori eradication in our clinical population . Patient compliance was excellent and attempts to increase compliance had no impact on outcome or compliance . Side effects were very common and were significantly associated with treatment failure and decreased compliance The effect of counselling on medication errors was assessed in 165 elderly patients after leaving hospital . Counselling was effective , with counselled patients making under one-third of the errors made by uncounselled patients . Three types of memory aid were tried to supplement counselling . The pill wheel increased errors , a tablet identification card was unhelpful , and only a tear-off daily calendar seemed to improve results modestly . Counselling was virtually as effective in improving compliance in poorly orientated patients . A design ated member of staff should spend about 15 minutes with each elderly patient before discharge to ensure that the discharge drug regimen is fully understood and remembered , that old tablets are destroyed and that other people 's tablets are not taken Three studies were carried out to determine the need , acceptability , and efficacy of adding mefloquine to artemisinin derivatives ( AD ) for the first-line treatment of uncomplicated falciparum malaria . The first was a retrospective study of 255 basic health workers which showed that their recommendation of AD to patients depended on their level of training . None of the paramedics/midwives and only 9 % of 129 doctors had prescribed AD , and no one had recommended AD in combination with mefloquine ; 72 % of patients used courses that were too short for parasitological cure . To promote the addition of mefloquine to AD regimens we conducted intervention workshops with health care providers and subsidized the cost of mefloquine to patients . In the second study , we interviewed 200 patients before and after the intervention to evaluate drug compliance with full doses of AD and use of subsidized mefloquine . After the intervention , we found that only 3.6 % had used mefloquine and 62 % had taken non-curative doses of AD . In the third study , we provided blister packs of medication in daily doses and compared the intake of AD + placebo ( 158 patients ) with that of AD + mefloquine ( 222 patients ) for 5 days . The compliance with both regimens was 99 % . Blood smears for parasites on day 28 showed one positive in the AD + mefloquine group and 7 positive in the AD group . We conclude that provision of blister packs of daily doses is a very effective way to improve compliance with short courses and drug combinations , but the efficacy of the combination in Myanmar in this particular study was only marginally higher than that of AD alone The objective was to determine the influence of medicine labels incorporating pictograms on the underst and ing of instructions and on adherence . Eighty-seven Xhosa participants attending an outpatient clinic who had been prescribed a short course of antibiotics were r and omly allocated to either a control group ( 41 participants given text-only labels ) , or an experimental group ( 46 participants given text + pictogram labels ) . All participants had a maximum of 10 years of formal schooling . Follow-up home visits were conducted after 3 - 5 days to assess underst and ing of instructions and to evaluate adherence . A high adherence of greater than 90 % was found for 54 % of the experimental group , compared with only 2 % of the control group . Average percentages for underst and ing in the control and experimental groups were 70 and 95 % , respectively , and average adherence was 72 and 90 % , respectively . The presence of pictograms was found to contribute positively to both underst and ing of instructions and adherence OBJECTIVE Compare the efficacy of a multicomponent social support intervention to st and ard-of-care counseling on medication adherence among HIV-infected patients initiating antiretroviral therapy . DESIGN R and omized controlled trial . Generalized estimating equations tested for differences in the percentage of participants achieving 90 % adherence . MAIN OUTCOME MEASURES Pill-taking , electronically monitored over 6 consecutive months ; plasma viral load ( VL ) , assessed at 3 and 6 months following initiation of therapy . RESULTS Of 226 participants who were r and omized and began the trial , 87 ( 38 % ) were lost to the study by 6 months . The proportion of adherent participants declined steadily over time , with no time by group interaction . Sustained adherence was associated with increased odds of achieving an undetectable VL ( OR=1.78 ; 95 % CI=1.01 , 3.13 ) . In intention-to-treat analyses , a larger proportion of the intervention group than the control group was adherent ( 40.15 % vs. 27.59 % , p=.02 ) and achieved an undetectable VL p=.04 ) . However , the majority of participants who remained on study experienced some reduction in VL ( > or=1-log drop or undetectable ) , regardless of experimental condition . CONCLUSION The multicomponent social support intervention significantly improved medication adherence over st and ard-of-care counseling ; evidence for improved virologic outcomes was inconsistent . Early discontinuation of care and treatment may be a greater threat to the health of HIV patients than imperfect medication-taking OBJECTIVE Patients with low health literacy have difficulty underst and ing prescription drug labels and other medication instructions . This article describes the development , implementation , and preliminary evaluation of an illustrated medication schedule ( a " pill card " ) that depicts a patient 's daily medication regimen using pill images and icons . METHODS Participants in a r and omized controlled trial who were assigned to receive the pill card intervention described their use of the card and its perceived effectiveness . Responses were analyzed by level of patient literacy and other characteristics . RESULTS Among the 209 respondents , 173 ( 83 % ) reported using the pill card when they initially received it , though use declined to 60 % approximately 3 months later . Patients with inadequate or marginal literacy skills , less than high school education , or cognitive impairment were most likely to refer to the card on a regular basis initially and at 3 months ( p<0.05 ) . Most pill card users ( 92 % ) rated the tool as very easy to underst and , and 94 % found it helpful for remembering important medication information , such as the name , purpose , or time of administration . CONCLUSION Nearly all patients considered an illustrated medication schedule to be a useful and easily understood tool to assist with medication management . Patients with limited literacy skills , educational attainment , or cognitive function referred to the aid with greater frequency . PRACTICE IMPLICATION S Picture-based instructions promote better underst and ing of prescription medications , particularly among patients with limited literacy skills or cognitive impairment , and should be used more widely in practice Adherence to medications is an important issue in oncology due to the increasing number of anticancer agents , such as targeted therapies , formulated for oral dosing . A prospect i ve , crossover design was utilized in which patients on capecitabine were r and omly assigned to one of two packaging methods for one cycle , and then switched over to the alternate packaging method in the subsequent cycle . Twenty-five patients were accrued to this study . Adherence rates were similar when using the daily pill boxes ( 17/21 = 81 % ) and when using the conventional pill bottles ( 18/21 = 86 % ) . However , more patients were satisfied with the daily pill boxes ( 61 % versus 11 % , P = 0.027 ) , preferred the daily pill boxes ( 61 % versus 17 % , P = 0.061 ) , and thought the daily pill boxes were more helpful in reminding them to take their medications ( 50 % versus 11 % , P = 0.070 ) . In conclusion , this small pilot study did not demonstrate that the use of daily pill boxes improved patient adherence with capecitabine , but patient satisfaction and preference for this packaging method were greater than for the conventional pill bottles . Further exploration of this intervention in a larger study is warranted To improve operational efficiency as well as to improve patient compliance in leprosy programmes , DANIDA introduced blister-calendar packs ( BCP ) to deliver MDT in 4 MDT districts in India in 1987 . An objective study ( Phase II ) involving 343 patients in a trial group ( BCP group ) and 253 patients in a control group ( loose drug group ) showed no significant difference in compliance rates for self-administered dose between the 2 groups . Hence , while assessing the use of BCPs in leprosy programmes , other operational benefits like safe storage , easy transportation , easy drug accounting and safe preservation at home are to be considered . These aspects were followed up from Phase I of the study A r and omised trial was undertaken to discern the effect of pharmacy-based value-added utilities on prescription refill compliance with antihypertensive therapy and subsequent health care expenditures . The subjects were 304 Medicaid beneficiaries from the state of Florida , previously untreated for mild to moderate hypertension , prescribed 240 mg of calcium channel antagonist verapamil once daily and monitored regarding prescription refill compliance and health service utilisation for one year . Subjects provided informed consent and were r and omly assigned to one of four experimental groups : ( 1 ) the control cohort received st and ard pharmaceutical care with each dispensing of antihypertensive therapy , ( 2 ) the second cohort received st and ard pharmaceutical care and was mailed a medication-refill reminder ten days prior to each sequential refill date , ( 3 ) the third cohort received st and ard pharmaceutical care and was provided unit-of-use packaging with each prescription-refill request and ( 4 ) the fourth cohort received st and ard pharmaceutical care , mailed medication-refill reminders and unit-of-use packaging . Analysis of variance ( ANOVA ) procedures revealed that patients receiving mailed prescription-refill reminders , unit-of-use packaging or a combination of both interventions achieved a significant ( P < or = 0.05 ) increase in the Medication Possession Ratio ( MPR ) for antihypertensive therapy relative to controls . Receipt of both interventions result ed in a significant ( P < or = 0.05 ) improvement in the MPR for antihypertensive therapy relative to all other groups no significant difference was discerned between groups receiving either mailed prescription-refill reminders or unit-of-use packaging . ( ABSTRACT TRUNCATED AT 250 WORDS Summary : Fifty‐three hospital out patients with epilepsy were r and omly allocated to either a control or an intervention group . Patients in the intervention group were subjected to a combination of compliance‐improving strategies : patient counselling , a special medication container , self‐recording of medication intake and seizures , and mailed reminders to collect prescription refills and attend clinic appointments . Compliance with anticonvulsant therapy ( as measured by plasma anticonvulsant levels and prescription refill frequencies ) , and seizure frequency , were evaluated in each patient prior to intervention and 6 months afterwards . Patient compliance and clinical control improved significantly in the intervention group patients . Seizure frequency was , on average , halved following intervention . Compliance and seizure frequency were unaltered in the control group . Intervention failed to improve clinic appointment keeping . Poor compliance with drug therapy commonly confounds the treatment of epilepsy . This study shows that compliance can be improved and seizure frequency lessened by strategies that are easily incorporated into the routine management of epileptic patients This 6-month r and omized controlled trial evaluated the impact on quality of life ( QOL ) of a medication reminder device for patients with HIV . Patients were eligible if they had taken three or fewer highly active antiretroviral therapy ( HAART ) regimens or were treatment naïve . The intervention group received the Disease Management Assistance System ( DMAS ) , a prompting device that verbally reminds patients at medication times and electronically records doses , and a monthly 30 minute adherence educational session . Controls received education only . QOL was measured at baseline and 6 months using the Centers for Epidemiologic Studies Depression Scale ( CES-D ) , Instrumental Activities of Daily Living ( IADLs ) , and the Medical Outcomes Study HIV Health Survey ( MOS-HIV ) . At baseline , 62 patients completed surveys ( 31 control , 31 DMAS ) ; at month 6 , 48 patients completed surveys ( 23 control , 25 DMAS ) . At month 6 , controls had improved QOL scores for CES-D , IADLs , physical health , general health , pain , QOL , and role functioning , while participants in the DMAS arm had some deterioration in QOL scores . These differences persisted after controlling for demographics , baseline CD4 , and adherence . DMAS was associated with improved adherence but decreased QOL Four compliance strategies were compared with education alone to investigate their impact on the control of high blood pressure . One hundred twelve subjects with documented high blood pressure were r and omly assigned to receive education alone , home blood pressure monitoring , contracts , pill packs , or a combination of techniques . Groups were similar in terms of age , sex , race , initial blood pressure , and medications . At the end of the year , there was no significant change in blood pressure for the group that received education alone ( -3/-1 mm Hg ) . There was a statistically significant change in both systolic and diastolic blood pressure for all compliance groups ( -17/-10 mm Hg ) . Information from compliance question naires adds further support to the observation that education alone does not influence compliance while the specific techniques studied did improve compliance . The study was too small to show any difference among techniques Malaria is a major cause of morbidity and mortality among children under five in sub-Saharan Africa . Prompt diagnosis and adequate treatment of acute clinical episodes are essential to reduce morbidity and prevent complications and mortality . In many countries , chloroquine syrup is the mainstay of malaria treatment for children under five . Not only is syrup more expensive than tablets , adherence to the prescribed dose at home is a problem because mothers use wrongly sized measuring devices or have difficulty with the instructions . We investigated the impact of introducing pre-packed tablets for children on adherence to treatment and compared the total cost of the tablets with that of syrup . Children aged 0 - -5 years diagnosed with malaria at the clinic over a 6-week period received either pre-packed tablets or syrup by r and om assignment . The principal caregivers were interviewed at home on day 4 after attending the clinic . Of the 155 caregivers given pre-packed tablets , 91 % ( n=141 ) adhered to the recommended dosage , while only 42 % ( n=61 ) of 144 who were provided syrup did . Only 20 % of caregivers who received syrup used an accurate 5 ml measure . The cost of treatment with tablets was about one-quarter that of syrup and 62 % ( n=96 ) of caregivers preferred tablets . Pre-packed chloroquine tablets are a viable alternative to syrup Given the burden of illness related to diabetes , hypertension and dyslipidemia , it is very important to achieve glycemic control , optimal blood pressure and low-density lipoprotein cholesterol ( LDL-C ) in order to avoid severe long-term complications . Patients ’ adherence with , and persistence to , the treatment regimen is a critical factor in achieving this goal . Medication taking behavior in these chronic , nonsymptomatic ( ‘ silent ’ ) diseases is generally low , although a wide range of results have been reported . The literature has shown that nonadherence to medications is a multidimensional phenomenon ; relating factors can be grouped into the following categories : health system related , social/economic , condition-related , therapy-related and patient-related factors . Although several interventions exist to improve patients ’ medication-taking behavior , none appear to be clearly superior to others . The key steps to improve adherence are to identify individual barriers and to develop patient-specific self-management plans to overcome them ( called ‘ patient-centric ’ approach ) . When developing intervention strategies one should always remember that ‘ one size does not fit all ’ . Well design ed ( but not r and omized ) , observational studies ( for example , patient registries ) may be required with sufficient follow-up periods and multiple adherence measurements in order to advance the field The combination of artesunate and mefloquine is currently one of the most effective treatments against multidrug-resistant Plasmodium falciparum malaria . To improve patient compliance to such a combination , the two agents have been combined in a prepacked single blister . Patients were instructed to simultaneously co-administer the drugs once a day for three days . In the present r and omized , double-blind , parallel group , comparative , single center study in Thail and , this concept was investigated in 204 adults and children with acute , uncomplicated P. falciparum malaria . Patients were r and omized into two treatment groups and received once a day over a three-day period the following : Group A received artesunate , 4 - 5 mg/kg/day , and mefloquine , total dose = 25 mg/kg , approximately 8.5 mg/kg/day , simultaneously . Group B received artesunate , 4 - 5 mg/kg/day , and mefloquine , total dose = 25 mg/kg , sequentially ( i.e. , no mefloquine dose on the first day , 15 mg/kg on the second day , and 10 mg/kg on the third day ) . Both treatment groups showed no relevant differences in baseline demographic and clinical characteristics . Intent-to-treat analysis revealed a cure rate at day 28 ( primary endpoint ) of 100 % in group A and 99 % in group B ( difference not significant ) . The secondary endpoints of mean time to fever clearance ( group A = 34 hours , group B = 31 hours ) and mean time to parasite clearance ( group A = 44 hours group B = 48 hours ) were similar between groups ( both differences not significant ) . Tolerability was good in both treatment groups , with no difference in the overall incidence of adverse events . There was a low incidence of nausea/vomiting ( 4.9 % in both groups ) and central nervous system side effects ( 4.9 % in group A versus 8.8 % in group B ) . These were comparable between groups and generally of a mild nature . The three-day combination of artesunate and mefloquine ( Artequin , Mepha , Ltd. , Aesch , Switzerl and ) with the introduction of mefloquine on day 1 offers a practical dosing regimen that is highly effective and well tolerated in patients of different ages with uncomplicated P. falciparum malaria . It is likely that the prepacked blister approach translates clinical ly into a better patient compliance , thereby contributing to limit the development of drug resistance A controlled trial of the effect of a unit dose system of tablet/capsule calendar packaging ( Webster-Pak ) on the rate of successful self medication both in hospital and after discharge to the community has been completed in a geriatric assessment and rehabilitation unit . Eighty-four elderly patients , 45 using calendar packs ( study ) , and 39 using conventional bottles or packs ( control ) , were followed for three months after discharge . There was a significant improvement in patient compliance in the study group over controls on discharge ( 86.7 % vs 66.7 % ) , 10 days ( 68.8 % vs 41.0 % ) , one month ( 64.4 % vs 38.5 % ) and three months ( 48.9 % vs 23.1 % ) after discharge . Unit dose packaging is a cost effective method of improving the delivery of medicine in elderly patients , and should be available as part of the health budget Purpose : To evaluate the accuracy of a prototype electronic device for recording eye drop usage . Participants and Methods : Ten volunteers were r and omly assigned to one of five usage patterns design ed to mimic common patterns of use in glaucoma patients from 100 % compliant to 50 % compliant . All participants agreed to adhere to a pre-determined “ dosing ” schedule for 15 days using the monitoring/reminder device to instill artificial tears . Participants also recorded drop usage in a diary . The main outcome measures were device accuracy and reproducibility . Device accuracy was defined as the magnitude of the difference between the diary and device output for three variables : date , number of drops , and instillation time . Results : Date stamping by the device was 100 % accurate . The mean ± SD time difference between the device and the diary was -2.0 ± 19.7 minutes when data from all participants was pooled . In seven of the ten participants , the device did not record at least one drop . The mean ± SD difference in the number of drops recorded by the device minus the diary was 0.16 ± 0.97 when data from all participants was pooled . Conclusions : The prototype compliance reminder/monitoring device may underestimate compliance in some patients . The date and time stamping mechanisms were generally accurate and reproducible In rural , malaria-endemic Burkina Faso , we evaluated the impact of the use of pre-packaged antimalarial drugs ( PPAM ) , by mothers in the home , on the progression of disease in children from uncomplicated fever to severe malaria . In each village of one province , a core group of opinion leaders ( mainly older mothers ) was trained in the management of uncomplicated malaria , including the administration of PPAM . Full courses of antimalarial ( chloroquine ) and antipyretic ( aspirin ) drugs were packaged in age-specific bags and made widely available through community health workers who were supplied through the existing drug distribution system . Drugs were sold under a cost-recovery scheme . Local schoolteachers conducted surveys in a r and om sample of 32 villages at the end of the high transmission seasons in 1998 and 1999 . Disease history and the treatment received were investigated for all children under the age of 6 years having suffered from a fever episode in the previous 4 weeks . ' Uncomplicated malaria ' was defined as every episode of fever and ' severe malaria ' as every episode of fever followed by convulsions or loss of consciousness . During the study period , 56%[95 % confidence interval ( CI ) 50 - 62 % ] of 3202 fever episodes in children under 6 years of age were treated promptly by mothers with the pre-packaged drugs made available by the study . A total of 59 % of children receiving PPAM were reported to have received the drugs over the prescribed 3-day period , while 52 % received the correct age-specific dose . PPAM use was similar among literate ( 61 % ) and non-literate mothers ( 55 % ) ( P = 0.08 ) . The overall reported risk of developing severe malaria was 8 % . This risk was lower in children treated with PPAM ( 5 % ) than in children not treated with PPAM ( 11 % ) ( risk ratio = 0.47 ; 95 % CI 0.37 , 0.60 ; P < 0.0001 ) . This estimate of the impact of PPAM was largely unchanged when account was taken of potential confounding by age , sex , maternal literacy status , year or village . Our findings support the view that , after appropriate training and with adequately packaged drugs made available , mothers can recognize and treat promptly and correctly malarial episodes in their children and , by doing so , reduce the incidence of severe disease Context Patients sometimes have difficulty following complicated treatment regimens . Contribution In this trial , 314 low-income patients with congestive heart failure were r and omly assigned to a pharmacist intervention or usual care . The pharmacist assessed patient knowledge and provided instructions about medication use . During the 9-month intervention , patients in the intervention group had greater medication adherence than patients in the usual care group ( 79 % vs. 68 % ) . These differences dissipated within 3 months of stopping the intervention . Patients in the intervention group also had fewer exacerbations result ing in emergency department visits or hospitalizations than patients in the usual care group . Implication Ongoing educational intervention by a pharmacist can improve medication adherence and outcomes in patients with heart failure . The Editors In the United States , 5 million people have heart failure , with total health care costs exceeding $ 29 billion ( 1 ) . These costs are largely derived from expensive exacerbations that require emergency visits and hospitalizations ( 1 , 2 ) . Regularly administered cardiovascular medications may preserve cardiac function , improve quality of life , and reduce risk for costly exacerbations . However , patients sometimes do not adhere to prescribed instructions and have poor outcomes ( 35 ) . Research ers have estimated that approximately 50 % of patients with chronic illnesses do not take their medications as prescribed ( 6 ) . Reasons for nonadherence include lack of patient knowledge , skills , and support to appropriately self-manage complicated medication regimens ( 7 , 8) . Although chronic disease management programs abound , few studies have rigorously tested interventions aim ed at improving patient adherence to prescribed medications and their effect on health outcomes ( 9 , 10 ) . We conducted a r and omized clinical trial to assess the effect of a pharmacist intervention on patients who are socioeconomically disadvantaged and medically vulnerable . We hypothesized that the intervention would improve adherence to heart failure medications , reduce exacerbations requiring emergency department visits or hospitalization , improve disease-specific quality of life , increase patient satisfaction , and reduce health care costs . Methods Design Overview The methods for our r and omized trial are described elsewhere ( 1113 ) . We recruited patients from the general medicine and cardiology practice s of Wishard Health Services , Indianapolis , Indiana , which serves socioeconomically disadvantaged and medically vulnerable patients . The study was conducted from February 2001 to June 2004 . Patients took part in the study for 12 months and received 9 months of active intervention by the pharmacist or usual care followed by 3 months of postintervention assessment . Patients in the usual care and intervention groups visited the same pharmacy location , but the intervention pharmacist was instructed to have no contact with patients in the usual care group . The institutional review boards of Indiana UniversityPurdue University and the University of North Carolina at Chapel Hill approved this study . Setting and Patients Indiana University Medical Group , Indianapolis , is an academic primary care group practice composed of primary and specialty care clinics affiliated with Wishard Health Services . Faculty physicians , residents , and nurse practitioners provide care to 13000 adults ( mean age , 57 years [ SD , 15 ] ; 60 % women ; 50 % African American ) . Annually , these patients make approximately 50000 visits to practice s , 72000 visits to emergency departments , and 135000 visits to pharmacies and have 16000 hospitalizations . We recruited patients from 4 identical general medicine practice s , 1 cardiology practice , and Wishard Memorial Hospital . Practice s met in half-day sessions per week that were attended by 2 or 3 faculty members and 3 to 5 residents or fellows from each practice . Faculty physicians practice d 1 to 5 half-days per week , whereas fellows practice d 1 to 2 half-days per week and residents attended the practice 1 half-day per week . Out patients of Wishard Health Services fill their prescriptions at central or de central ized outpatient pharmacies located at the ambulatory care center or at 1 of several satellite pharmacies stationed at neighborhood clinics . Fully stocked de central ized pharmacies serviced all study patients . From February 2001 to January 2003 , the study pharmacy was located in a building adjacent to the ambulatory care center . From February 2003 to June 2004 , the study pharmacy was moved to a space adjacent to the general medicine practice s in the ambulatory care center . Two pharmacists and 1 technician were stationed at the pharmacy . The study pharmacist was instructed to service patients in the intervention group only , and a second pharmacist serviced patients in the usual care group and filled prescriptions to be delivered to patients at outlying clinics . The technician filled prescriptions and read electronic adherence monitors . Weekly lists of eligible patients were created by using the Regenstrief Medical Record System ( Regenstrief Institute , Indianapolis , Indiana ) ( 14 , 15 ) . We invited clinical ly stable patients from general internal medicine practice s , a cardiology clinic , and Wishard Memorial Hospital ( at discharge ) to participate in the study . Of 3034 patients with a diagnosis of heart failure , 1512 met criteria for enrollment . Patients were eligible if they were 50 years of age or older ; planned to receive all of their care , including prescribed medications , at Wishard Health Services ; had a diagnosis of heart failure confirmed by their primary care physician ; regularly used at least 1 cardiovascular medication for heart failure ( angiotensin-converting enzyme [ ACE ] inhibitor or angiotensin-receptor blocker , -adrenergic antagonist , diuretic , digoxin , or aldosterone antagonist ) ; were not using or were not planning to use a medication container adherence aid ( for example , a pill box ) ; had access to a working telephone ; and could hear within the range of normal conversation . We excluded patients with dementia . Patients received their prescription medications through state and local assistance plans at no cost . Thus , cost of medicines was not a deterrent to adherence . R and omization A trained interviewer conducted a baseline interview at enrollment . Interviewers were blinded to patients ' study status and played no role in the delivery of the intervention . Interviewers contacted a central ized data manager at the end of each interview to determine the patient 's study assignment , which was otherwise concealed . We r and omly assigned patients , without blocking or stratification , to receive the pharmacy intervention or usual care by using a univariate discrete distribution from the IMSL Fortran Library 's subroutine RNGDA pseudor and om number generator ( Absoft Corp. , Rochester Hills , Michigan ) ( 16 ) . We r and omly assigned more patients to the usual care group so that this group could also be a prospect i ve cohort for study ing risk factors associated with the clinical deterioration of heart failure . Of the 314 patients included in the study , 229 were recruited from the general internal medicine practice s , 15 from the cardiology clinic , and 70 on discharge from the Wishard Memorial Hospital . The numbers of patients assigned to the intervention and usual care groups did not differ by recruitment site ( P= 0.83 ) . Intervention A pharmacist delivered the intervention by using a protocol ( Appendix Table 1 ) that included a baseline medication history of all prescription and over-the-counter drugs and dietary supplements taken by patients , which patients brought with them to the baseline interview , and the results of an assessment of patient medication knowledge and skills ( 7 , 8) . The pharmacist dispensed enough of the patient 's medications to last approximately 2 months . Appendix Table 1 . Pharmacist 's Intervention Protocol * When medications were dispensed , the pharmacist provided patient-centered verbal instructions and written material s about the medications ( 11 , 13 , 17 ) by using a schema for instruction that has been tested ( 18 , 19 ) . We assigned each medication category an icon ( for example , the icon for ACE inhibitors was a red ace of hearts ) . The same icon appeared on the container label and lid and on the written patient instructions . Written instructions were aim ed at patients with low health literacy and contained an easy-to-follow timeline to remind patients when to take their medications ( 13 ) . The pharmacist monitored patients ' medication use , health care encounters , body weight , and other relevant data by using a study data base ( 20 , 21 ) . Information about patients was communicated as needed to clinic nurses and primary care physicians by face-to-face visits , telephone , paging ( physician only ) , and e-mail ( physician only ) . Technicians supported the pharmacist 's dispensing efforts within the pharmacy throughout the study . We incorporated costs therein into the economic analysis . Pharmacists serviced patients in the usual care group who were not associated with the intervention or the study . An interdisciplinary team of investigators that included pharmacists with advanced training in patient education and cardiovascular pharmacotherapy , a geriatrician , a cardiologist with expertise in heart failure , a behavioral scientist , and a cognitive psychologist trained the intervention pharmacist . The intervention pharmacist also studied guidelines for treating heart failure ( 22 ) , key concepts in the pharmaceutical care of older adults , communication techniques , and the pharmacotherapy of the cardiovascular drugs for heart failure . All pharmacists at Wishard Health Services were aware of the study and were instructed on how to h and le and redirect intervention patients who inadvertently arrived at their pharmacy . Usual Care Patients in the usual care group were aware of the purpose of the study , and their primary care Electronic interactive technology is being used in medical care to enhance communication between the patient and health care provider , as well as the patient ’s performance of appropriate health behaviors . Research has demonstrated the value of technology in enhancing medication-taking behavior , capturing medicationtaking events , and generating reports to health care providers.1–4 These devices can capture other patient-specific information such as blood pressure , presence of symptoms , and functional status in “ real time ” rather than depending on patient recall at a later date . What is lacking in these studies is a clear view of how medication management devices fit with existing patient monitoring and feedback processes , which depend on the interaction between patients and their health care providers . Clinical endpoints are also lacking . We had the opportunity to conduct a pilot study of a medication management system that used patient-specific information to tailor the electronic interactive technology to each individual patient ’s needs and behaviors OBJECTIVE To evaluate medication adherence and treatment outcomes in elderly out patients using daily-dose blister packaging ( Pill Calendar ) compared with medications packaged in bottles of loose tablets . DESIGN R and omized controlled trial . SETTING Ambulatory care clinics at Ohio State University Medical Center , Columbus ; University of Arizona Health Science Center , Tucson ; and Riverside Method ist Hospital Family Medicine Clinic , Columbus , Ohio , from July 1 , 2002 , to December 31 , 2004 . PATIENTS 85 individuals 65 years of age or older being treated with lisinopril for hypertension . INTERVENTION Patients were r and omly assigned to receive lisinopril in either daily-dose blister packaging ( Pill Calendar ) or traditional bottles of loose tablets . MAIN OUTCOME MEASURES Adherence was assessed by prescription refill regularity and medication possession ratio ( MPR ) . Treatment outcome and use of medical services were assessed by medical record review of blood pressure and morbidity associated with poorly controlled hypertension . RESULTS Patients receiving lisinopril in the daily-dose blister packaging ( Pill Calendar ) refilled their prescriptions on time more often ( P = 0.01 ) , had higher MPRs ( P = 0.04 ) , and had lower diastolic blood pressure ( P = 0.01 ) than patients who had their medications packaged in traditional bottles of loose tablets . CONCLUSION Providing medications in a package that identifies the day each dose is intended to be taken and provides information on proper self-administration can improve treatment regimen adherence and treatment outcomes in elderly patients A prospect i ve , controlled , crossover study on drug compliance was initiated in 22 elderly patients from a geriatric clinic . Half of the patients received their pills from a commercially prepared calendar mealtime blister-pak ; the remaining patients received their medication from st and ard pill bottles . At the end of three months the two groups were crossed over . Pill count and issuance of a new drug supply were done monthly to assess compliance . It was found that the average noncompliance index was significantly decreased ( 9.17 to 2.04 ) with the blister-pak packaging system . The relationship of age , Folstein mini-mental status , overcompliance , frequency of dosing interval , and living situation were also explored This pilot study investigated the effects of three different medication management approaches on medication adherence and re source utilization . Sixty-one participants living in an independent elder community in South Florida were r and omly assigned to one of the three medication management approaches : ( 1 ) a pillbox method , ( 2 ) a voice-activated method , and ( 3 ) self-administration of medications as they had in the past . One outcome was measured by recording the number of doses of medications ingested over a 1- , 3- , and 6-month period . Adherence to medications also was measured by the impact on the medical diagnosis . For example , the hypertensive group was defined adherent by a sustained normotensive pressure . Participants ' medical records were examined as to the number of physician office visits , hospitalizations , and home health visits . There were significant differences in the mean number of doses missed , with the fewest in the voice-activated group to the highest in the self-administration ( control ) group . Additionally , the group that self-administered their own medications had more frequent physician office visits and increased hospitalizations . Because the elder population is prone to medication mismanagement for a variety of reasons , nurses are in a unique position to identify population s at risk and suggest interventions that may improve medication adherence In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies Background High blood pressure ( BP ) significantly increases overall cardiovascular risk , the incidence of ischemic heart disease and stroke . One of the most important causes of insufficient BP control is low treatment compliance . Reminders and electronic compliance monitoring have been shown to be effective in improving patient compliance to some extent , but the combined effect has not been documented . Objective To assess the impact of an electronic reminder and monitoring device on patient compliance and BP control . Methods All patients received medical treatment with telmisartan once daily and were r and omized to either electronic compliance monitoring with a reminder and monitoring device or st and ard therapy for 6 months . Both groups were crossed over after 6 months . Intervention effectiveness was assessed using self-reported compliance and BP . Results Data from 398 patients were analysed . In the first half of the study , patients using the device reported 91 % compliance versus 85 % in the control group . This difference diminished after crossover ( 88 versus 86 % ) . BP was not affected . Electronic monitoring data on compliance revealed taking , dosing and timing compliance between 45 and 52 % in study group 1 , and between 32 and 38 % in study group 2 . Conclusion The Helping H and reminder device was most suitable if used for newly diagnosed hypertensive patients , when it improved compliance by 6 % . With the present medical treatment , the device does not have any influence on BP control , but with less forgiving medications , the device might make a significant difference . The use of the device can be an easy and effective way to improve compliance in selected patients The impact of pill organizers on pill taking was determined in the Trial of Antioxidant Vitamins C and E ( TRACE ) Study , a factorial trial of vitamin C and vitamin E supplementation in 184 individuals . Participants were recruited in 1996 - 1997 and r and omized to one of two groups ( pill organizer or no organizer ) and to one of four supplement groups for 2 months . The pill count ( observed/expected X 100 % ) distribution was similar in the organizer and no organizer group for both vitamins . Mean differences in changes in serum vitamin levels between active and placebo groups did not differ by pill organizer use . The impact of pill organizers and blister packs was compared in another trial , the Vitamins , Teachers , and Longevity ( VITAL ) Study , in 297 individuals r and omized in 1993 - 1994 to receive study pills either in blister packs or in pill organizers and to take one of two supplements . Among those with lower adherence , the pill count distribution in the blister-pack group exceeded that in the organizer group . Mean differences in serum vitamin E levels between active and placebo groups did not differ by types of pill packaging . In summary , use of blister packs , but not pill organizers , improved adherence as measured by pill counts among those with lower adherence . Neither pill delivery system improved adherence as measured by serum vitamin levels Background : The relationship between patient adherence and treatment outcomes has been documented across chronic health conditions , but the evidence base for effective adherence interventions in human immunodeficiency virus ( HIV ) and acquired immune deficiency syndrome ( AIDS ) requires more rigorous research and reporting . Objectives : The aims of this study were to determine whether a tailored , nurse-delivered adherence intervention program-Client Adherence Profiling and Intervention Tailoring (CAP-IT)-improved adherence to HIV medications , compared with st and ard care , and to identify the relationship among adherence measures . Methods : A r and omized controlled trial ( RCT ) with repeated measures was used to test the efficacy of CAP-IT over a 6-month period . A convenience sample of 240 participants was recruited from a freest and ing public HIV/AIDS clinic in Houston , TX , that provides medical , psychological , and pharmaceutical services for over 5,000 clients . Study instruments and measures included demographics ; chart audit to capture CD4 count , viral load , and prescribed medications ; health literacy ; and five measures of adherence ( AIDS Clinical Trial Group-Revised Reasons for Missing Medications , Morisky Self-Report of Medication Non-Adherence , Pill Count , Medication Event Monitoring System [ MEMS ] caps , and Pharmacy Refill ) . Results : A logistic regression using generalized estimating equations method showed no significant differences over time on the five medication-adherence measures between the experimental and control groups . Little correlation was documented among the five different adherence measures , and there was minimal correlation with clinical markers . Discussion : It is unclear why the tailored adherence intervention was not efficacious in improving medication adherence . The findings suggest that these measures of medication adherence did not perform as expected and that , perhaps , they are not adequate measures of adherence . Effective and efficient adherence interventions are needed to address the barriers to medication adherence in HIV/AIDS Three instruction schemes for self-medication in older patients were design ed and compared to see whether they improved drug compliance . Forty-six patients in two rehabilitation units were divided into three different groups . Each group was instructed verbally on the nature and amount of their medication . One group was also given a tear-off calendar and a second group a tablet identification card as a memory aid . Patients were then responsible for taking their own medicine for 14 days . Those with calendars made fewer errors than those with cards , and those with either a card or a calendar made significantly fewer errors than those given only st and ard instructions A study of adherence to treatment was conducted by 179 general practitioners in elderly out patients with geriatric cerebral symptomatology treated with pentoxifylline . The drug was provided in 2 different r and omized packages , with or without memory‐aid stickers ( also r and omized ) . Compliance was assessed by pill count after 1 mo of treatment . Clinical evolution was assessed by a digit‐span test , and by filling in 9 “ relative ” visual analogue scales of aggravation — improvement . Side effects were recorded from patient complaints . Leftover drug was brought back by 83.1 % of patients , and this proportion was influenced neither by packaging type nor memory‐aid stickers . Compliance was considered good ( fewer than 30 tablets returned ) in 62 % of patients , and was not influenced by either packaging types or stickers . Peaks of pill count were evident at multiples of packaging units ( 10 or 40 according to type ) . Compliance was not related to age or sex , but was related to memory score . There was a correlation between compliance and clinical improvement , and a significant inverse correlation between the former and the frequency of side effects OBJECTIVE : To determine the effect of unit-of-use drug packaging of medications on compliance among elderly out patients treated with complex medication regimens . DESIGN : Nonblind , r and omized , clinical trial . SETTING : Geriatric outreach health centers in urban public housing units for independent-living elderly people . PATIENTS : Thirty-one patients ( aged ≥60 y ) , each taking three or more prescribed medications . Patients were r and omly assigned to one of three study groups : Group 1 ( n=12 ) , no change in dosing or packaging ; group 2 ( n=10 ) , conventional packaging with twice-daily dosing ; group 3 ( n=9 ) , unit-of-use packaging with twice-daily dosing . INTERVENTION : A unit-of-use package consisting of a two-ounce plastic cup with a snap-on lid containing all medications to be taken at the time of dosing . MAIN OUTCOME MEASURES : Medication compliance was assessed monthly for six months using tablet counts . RESULTS : Medication compliance was significantly better in group 3 ( 92.6 percent ) using unit-of-use packaging compared with either group 1 ( 79 percent ) or group 2 ( 82.6 percent ) ( p=0.017 ) . Compliance did not differ between groups 1 and 2 . CONCLUSIONS : In this small study of elderly out patients taking three or more medications , unit-of-use packaging and twice-daily dosing improved medication compliance compared with conventional packaging The effects on adherence and depressive symptoms of a community pharmacy-based coaching program , including a take-home videotape , were evaluated in a r and omized controlled trial in the Netherl and s. A total of 147 depressed primary care patients who had a new antidepressant prescription were included in the study . Adherence was measured with an electronic pill container and was also derived from pharmacy medication records ; the latter method was associated with an overestimation of adherence of only 5 percent . Intention-to-treat analyses showed no intervention effect on adherence ( 73 percent compared with 76 percent ) , whereas analyses of patients who received the intervention ( per protocol ) showed improved adherence ( 73 percent compared with 90 percent ) . Neither analysis showed effects on depressive symptoms OBJECTIVE To assess the impact of calendar blister pack ( CBP ) use on glycemic and blood pressure control . RESEARCH DESIGN AND METHODS We conducted an 8-month r and omized controlled double-blind study among diabetic patients with poor glucose control ( HbA1c > 9.0 % ) in an urban area of South Auckl and , New Zeal and , with a high proportion of Maori and Pacific Isl and s people . Subjects included 68 consecutive patients , of whom 50 % were prescribed three or more medications per day RESULTS HbA1c was reduced by 0.95+/-0.22 % in the CBP group and 0.15+/-0.25 % in the control group ( P = 0.026 ) . Diastolic blood pressure decreased 5.8+/-1.5 mm Hg in the CBP group and increased 0.1+/-1.9 mm Hg in the control group ( P = 0.0041 ) . Systolic blood pressure did not change significantly CONCLUSIONS CBPs should be considered among diabetic patients with poor glycemic control receiving multiple medications CONTEXT Poor adherence to treatment remains a major obstacle to efficient tuberculosis ( TB ) control in developing countries . Innovative strategies to improve access and adherence to treatment are needed . OBJECTIVES To assess the effectiveness of a context ualized intervention strategy aim ed at improving patients ' adherence to treatment and to evaluate its impact on TB control in a re source -poor country in Africa with prevalent TB infection . DESIGN , SETTING , AND PATIENTS A cluster r and omized controlled trial , conducted between June 2003 and January 2005 , at 16 government district health centers in Senegal . Patients older than 15 years with newly diagnosed sputum smear-positive pulmonary TB were r and omly assigned to the intervention or control group . INTERVENTION The intervention strategy included reinforced counseling through improved communication between health personnel and patients , de central ization of treatment , choice of directly observed therapy ( DOT ) supporter by the patient , and reinforcement of supervision activities . In the control group , the usual TB control program procedures remained unchanged . MAIN OUTCOME MEASURE Proportion of patients successfully completing the 8-month course of treatment and the proportion of patients defaulting from treatment . RESULTS A total of 1522 patients were recruited into the study . Treatment was successful for 682 ( 88 % ) of 778 patients recruited in the intervention group , and for 563 ( 76 % ) of 744 patients recruited in the control group ( adjusted risk ratio [ RR ] , 1.18 ; 95 % confidence interval [ CI ] , 1.03 - 1.34 ) . The proportion of patients defaulting was reduced in the intervention group to 5.5 % ( n = 43 ) compared with 16.8 % ( n = 125 ) in the control group ( adjusted RR , 0.43 ; 95 % CI , 0.21 - 0.89 ) . CONCLUSION The intervention package based on improved patients counseling and communication , de central ization of treatment , patient choice of DOT supporter , and reinforcement of supervision activities led to improvement in patient outcomes compared with the usual TB control procedures . This approach may be generalized in the context of TB control programs in re source -poor countries . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00412009 Our aim was to determine if a comprehensive adherence package improved self reported adherence to antiretroviral therapy . The adherence package included an education programme , individualized planning of regimens , and the opportunity for a patient to choose from a number of adherence aids and reminder devices . A r and omized step wedge design was used . Forty-three individuals were r and omized to begin the intervention over a five-month period . There was a substantial fall in the number of missed doses reported for the last four days ( 0.76 to 0.38 , P = 0.03 ) and last seven days ( 1.5 to 0.74 , P = 0.005 ) but not for the last 28 days ( 2.5 to 2.5 , P = 0.63 ) . There was no statistical difference in the viral load or CD4 lymphocyte count in the period before or after the intervention . The Morisky score during the pre and post intervention periods was significantly different ( P = 0.006 ) , 2.9 ( SD 0.9 ) and 3.3 ( SD 0.8 ) respectively . This adherence package improved self reported adherence during the last four and seven days OBJECTIVES This a priori subgroup analysis was conducted to assess patients ' experience with a compliance device for the administration of sublingual specific immunotherapy for grass pollen-induced rhinoconjunctivitis . METHODS The present paper reports the results of a subgroup analysis of a multicenter , r and omized , controlled , open-label European study in which adults with grass pollen-induced rhinoconjunctivitis received once-daily treatment with grass allergen tablets with or without a device to aid compliance . Treatment was given approximately 6 to 12 weeks before the grass pollen season , during the season ( approximately 8 - 10 weeks ) , and for up to 2 weeks after the end of the season . In the subgroup analysis , patients from Germany and the Netherl and s who had been r and omized to receive the compliance device were asked to complete a brief question naire at the final study visit . The question naire included 6 items concerning patients ' use of the device and whether it helped them remember to take their tablets . RESULTS Of the 91 patients from Germany and the Netherl and s who were r and omized to use the compliance device along with grass allergen tablets , 71 returned the question naire . Among responders , 58 of 71 ( 82 % ) reported using the device sometimes or always , 50 of 63 ( 79 % ) found the device easy to use , 32 of 69 ( 46 % ) found that the device made it easier to remember to take tablets , and 43 of 71 ( 61 % ) indicated that they would consider using the device again . CONCLUSION Most patients in this subgroup analysis used the compliance device as a medication reminder and rated it easy to use |
1,661 | 29,962,116 | For non-cavitated lesions , the use of sealants is supported by strong evidence , while the evidence for infiltration of proximal lesions is moderate .
The use of the ART technique to restore cavitated lesions is also supported by strong evidence as a suitable strategy that has been used extensively in the literature concerning non-dental setting s. Preservation of tooth structure through the use of MI treatment for both non-cavitated and cavitated lesions is supported by moderatestrong evidence , which supports the paradigm shift towards routine use of more conservative strategies in the treatment of carious lesions | Result ing in a high economic and biological cost , the traditional therapeutic approach to carious lesion management is still largely restorative .
Minimally invasive ( MI ) treatment offers an attractive alternative to managing carious lesions in a more conservative and effective manner , result ing in enhanced preservation of tooth structure .
The aim of this review was to summarize the evidence behind several MI alternatives for carious lesion management , including the use of sealants , infiltration , atraumatic restorative treatment ( ART ) , and selective carious tissue removal ( e.g. , indirect pulp capping , stepwise removal , or selective removal to soft dentine ) . | Dental caries remains a major public health problem , especially for certain high-risk population groups . The goal of this study was to assess the evidence regarding strategies meant to be used as alternatives or booster/supplements to fluoride for caries prevention and management . Articles were selected for inclusion if they had a prospect i ve longitudinal design , with a fluoride control arm , and were conducted in human subjects . Of the included studies , 7/18 studies on calcium-based strategies favored the test product ( the majority of studies included exposure of fluoride in all groups ) . All the arginine studies ( 8/8 ) included a combination of arginine and a calcium base , and concluded that this has the potential to significantly boost the performance of fluoride . The remaining included studies focused on the addition of microbial-related strategies to a fluoride-containing vehicle ( 2 xylitol studies and 1 study using a probiotic milk ) , and all favored the combination as a booster to fluoride . Thus , the current study did not identify evidence for any strategy to effectively be used as a substitute or alternative to fluoride , but identified some consistent evidence derived from the use of prebiotic strategies ( primarily from use of arginine combined with calcium ) to support their potential use to boost the mechanism of action of fluoride . Thus , fluoride-based strategies remain the st and ard for caries prevention and management , with some evidence that boosting the effects of fluoride by the use of prebiotic strategies is a promising possibility Objective : Considering the minimally invasive approach to dentistry , the scientific community has focused on non-invasive treatments for caries lesions . The aim of this study was to evaluate the efficacy of a nonsurgical approach to arrest occlusal non-cavitated dentin lesions through glass ionomer sealing . Methods : In this controlled clinical trial , 51 teeth with clinical ly non-cavitated occlusal caries radiographically located beneath the enamel-dentine junction ( radiolucent area ) were selected among patients presenting a moderate to high risk of caries . The teeth were r and omly divided into two groups : an experimental group receiving an application of Vidrion-R ( SS White ) glass ionomer and a control group not su bmi tted to any clinical intervention . Caries progression was monitored by clinical and radiographic examination at 4-monthly intervals over a period of one year . In addition , marginal integrity of the sealant was evaluated in the experimental group . Results : Clinical examination showed no statistical difference between the groups ( P=.13 ) . On the other h and , sealed teeth presented lower caries progression when analyzed by radiographic examination ( P=.004 ) . Conclusion : A glass ionomer sealant over non-cavitated occlusal caries lesions in dentin may not be sufficiently effective in arresting their progression Concern about the survival of microorganisms in deep carious lesions may often lead to unnecessary exposure of the pulp during final excavation . There are reasons , therefore , to initiate systematic studies on the alternative procedure known as stepwise excavation . Clinical evaluation of stepwise excavation was performed on 31 deep carious lesions considered to result in pulp perforation by traditional excavation . This study examines the clinical and microbiological alterations during the final excavation performed during long intervals ( 6 - 12 months ) after the initial treatment that included peripheral dentine excavation and removal of the central cariogenic biomass and the superficial necrotic dentine . The dentine colour and consistency were assessed by means of st and ardized scales before application of a Ca(OH)2 compound and a temporary sealing for 6 - 12 months . Re assessment s were performed before the after final excavation . Microbiological dentine sample s were obtained in 19 r and omly selected lesions by a sterile bur , transferred to and diluted in reduced transport fluid , and plated on tryptic soy agar . After anaerobic incubation at 37 degrees C for 7 days , total colony-forming units per millilitre were counted from ( 1 ) peripheral excavated and hard dentine ( control ) , ( 2 ) central demineralized dentine before and final excavation , and ( 3 ) central dentine after the final excavation . Six sample s of central demineralized dentine were without any cultivable flora increasing to 9 sample s after the final excavation . The clinical dentine changes occurring during stepwise excavation were characterized by enhanced hardness of the dentine which was associated with a marked reduction in bacterial growth after the final excavation . Despite the presence of bacteria in the excavated dentine none of the carious lesions result ed in pulp perforation , suggesting that the initial removal of the cariogenic biomass appears to be essential for control of caries progression . Stepwise excavation is not only an appropriate treatment of deep carious lesions but is also considered a suitable model for microbiological studies to determine the bacteria persisting in clinical ly excavated lesions OBJECTIVE The objective of this study was to assess radiographic outcomes after partial carious dentin removal performed in deep caries lesions over a 10-year period . STUDY DESIGN Baseline image was compared to 3 follow-up radiographs ( at 6 - 7 months , 3 years , and 10 years ) . Tertiary dentin deposition and lesion depth were qualitatively assessed . Radiographic density changes in the radiolucent zone ( RZ ) beneath the restoration were quantitatively compared to the control areas ( CA ) using digital subtraction radiography ( Friedman repeated- measures analysis of variance ) . RESULTS A total of 13 teeth were evaluated . In most cases , lesion depth remained unchanged or decreased ( 12/13 ) and tertiary dentin formation was observed ( 10/13 ) after the 10-year follow-up . Differences between RZ and CA at the 6- to 7-month and 3-year follow-up periods were similar but significantly lower than those at the 10-year assessment . CONCLUSIONS Sealing of carious dentin arrested the caries process , promoted deposition of tertiary dentin , and induced mineral gain in the radiolucent zone PURPOSE To follow-up teeth with deep caries lesions su bmi tted to incomplete caries removal over a 10-year period . METHODS 27 subjects ( 32 permanent posterior teeth ) with deep caries lesions composed the sample . In this single-arm long-term prospect i ve study , the inclusion criteria were risk of pulp exposure during caries excavation , positive response to the cold test , absence of spontaneous pain or sensitivity during percussion , and radiographic absence of a periapical lesion . Subjects were su bmi tted to the following procedures : complete caries removal from the surrounding cavity walls , incomplete caries removal from the pulpal wall , capping with a calcium hydroxide cement , and sealing with a modified zinc oxide-eugenol cement . After 6 - 7 months , the temporary sealing was removed for method ological purpose s ( no further excavation was performed ) , and teeth were capped with a calcium hydroxide cement and filled with resin composite . Clinical and radiographic assessment s were conducted after 6 - 7 months , 1.5 , 3 , 5 and 10 years . Success was defined as clinical and radiographic signs and symptoms of pulp sensitivity while failure was defined as endodontic treatment need . RESULTS Over 10 years , one tooth was excluded from the sample ( pulp exposure during treatment ) , five were lost to recall , 10 had therapy failure ( five fractures and four necroses leading to endodontic treatment need , and one extraction ) and 16 had therapy success ( pulp sensitivity ) . Overall survival rates were 97 % , 90 % , 82 % and 63 % at 1.5- , 3- , 5- and 10-year follow-ups , respectively . Teeth with two or more restored surfaces failed significantly more than teeth with one restored surface ( P= 0.01 ) Less invasive excavation methods have been suggested for deep caries lesions . We tested the effects of stepwise vs. direct complete excavation , 1 yr after the procedure had been carried out , in 314 adults ( from six centres ) who had received treatment of a tooth with deep caries . The teeth had caries lesions involving 75 % or more of the dentin and were central ly r and omized to stepwise or direct complete excavation . Stepwise excavation result ed in fewer pulp exposures compared with direct complete excavation [ difference : 11.4 % , 95 % confidence interval ( CI ) ( 1.2 ; 21.3 ) ] . At 1 yr of follow-up , there was a statistically significantly higher success rate with stepwise excavation , with success being defined as an unexposed pulp with sustained pulp vitality without apical radiolucency [ difference : 11.7 % , 95 % CI ( 0.5 ; 22.5 ) ] . In a subsequent nested trial , 58 patients with exposed pulps were r and omized to direct capping or partial pulpotomy . We found no significant difference in pulp vitality without apical radiolucency between the two capping procedures after more than 1 yr [ 31.8 % and 34.5 % ; difference : 2.7 % , 95 % CI ( -22.7 ; 26.6 ) ] . In conclusion , stepwise excavation decreases the risk of pulp exposure compared with direct complete excavation . In view of the poor prognosis of vital pulp treatment , a stepwise excavation approach for managing deep caries lesions is recommended BACKGROUND More conservative techniques for managing dental caries including ' partial ' and ' no caries removal ' have been increasingly of interest . AIM To compare children 's behaviour and pain perception , also technique acceptability ( parents and dentists ) , when approximal dentinal lesions ( ICDAS 3 - 5 ) in primary molars ( 3 - 8-year-olds ) were managed with three treatment strategies ; conventional restorations ( CR ) , hall technique ( HT ) , and non-restorative caries treatment ( N RCT ) . DESIGN Secondary care-based , three-arm parallel-group , r and omised controlled trial , with 169 participants treated by 12 dentists . OUTCOME MEASURES child 's pain perception ( Visual Analogue Scale of Faces ) ; behaviour ( Frankl scale ) ; and parents ' and dentists ' treatment opinions ( 5-point Likert scales ) . RESULTS Children showed more negative behaviour in the CR group ( 37 % ) compared to N RCT ( 21 % ) and HT ( 13 % ) ( P = 0.047 , CI = 0.41 to 0.52 ) . Pain intensity was rated ' very low ' or ' low ' in 88 % N RCT , 81 % HT , and 72 % CR ( P = 0.11 , CI = 0.10 to 0.12 ) . N RCT and HT were ' very easy ' or ' easy ' to perform for > 77 % of dentists , compared to 50 % in CR group ( P < 0.000 ) . There were no statistically significant differences in parents ' rating of their child 's level of comfort ( P = 0.46 , CI = 0.45 to 0.48 ) . CONCLUSIONS Dentists reported more negative behaviour in CR group . For all techniques , children 's pain perception and dentist/parent acceptability were similar OBJECTIVE To evaluate the clinical performance of atraumatic restorative treatment ( ART ) fillings using Fuji IX as a filling material in field conditions . DESIGN Longitudinal study of the ART fillings in permanent teeth of primary school children aged eight to fifteen years . SETTING Primary schools in Morogoro municipality , Tanzania . SUBJECTS AND METHODS St and ard 3 and 4 children in five primary schools r and omly selected from a list of 36 primary schools of Morogoro municipality were examined for dental caries and periodontal conditions . All 296 carious lesions that were indicated for restoration were treated using ART approach according to the instructions given in the manual for ART approach for the control of dental caries . Essential measurements for treated teeth and cavity were taken . The cavities were filled with Fuji IX glass ionomer cement as per manufacturer 's instructions . After one year , 238 restorations were evaluated using the criteria for evaluating ART restorations . MAIN OUTCOME MEASURE Clinical appearance of the surface of the restorations . RESULTS Ninety four per cent of the restorations evaluated were rated as good and intact , while 1.7 % were rated as having slight defects that needed no repair , giving a one year survival rate of 96.1 % . Mean working time was 14.5 minutes . CONCLUSIONS AND RECOMMENDATIONS The one-year survival rate of 96.1 % is high enough to recommend wide use of ART in Tanzania . Town and municipal councils should be encouraged to adopt ART in their school oral health programmes Resin infiltration is an innovative approach to arrest progression of caries lesions . The aim of this r and omized split-mouth placebo-controlled clinical trial was to assess whether resin infiltration of proximal lesions is more effective than non-operative measures alone with respect to the inhibition of caries progression . In 22 young adults , 29 pairs of interproximal lesions with radiological extension into the inner half of enamel or the outer third of dentin were r and omly allocated to two treatment groups . In the test group , lesions were infiltrated ( Icon , pre-product ; DMG ) . A placebo treatment was performed in the control group . All participants received instructions for diet , flossing , and fluoridation . The primary outcome after 18 months was radiographic lesion progression ( assessed by digital subtraction radiography ) . No unwanted effects could be observed . In the effect group , 2/27 lesions ( 7 % ) and in the control group 10/27 lesions ( 37 % ) showed progression ( p = 0.021 ; McNemar ) . Infiltration of interproximal caries lesions is efficacious in reducing lesion progression This r and omized , multicenter clinical trial evaluated the effectiveness of 2 treatments for deep caries lesions — partial caries removal ( PCR ) and stepwise excavation ( SW ) — with respect to the primary outcome of pulp vitality for a 3-year follow-up period . Inclusion criteria were as follows : patients with permanent molars presenting deep caries lesions ( lesion affecting ≥ 1/2 of the dentin on radiographic examination ) , positive response to a cold test , absence of spontaneous pain , negative sensitivity to percussion , and absence of periapical lesions ( radiographic examination ) . Teeth r and omly assigned to PCR ( test ) received incomplete caries removal and filling in a single session . Outcome success was evaluated by assessment of pulp vitality , determined by pulp sensitivity to a cold test and the absence of periapical lesions . Data were analyzed by a Weibull regression model with shared frailty term ( survival analysis ) . At baseline , 299 treatments were executed : PCR , 152 and SW , 147 . By the end of the 3-year follow-up period , 213 teeth had been evaluated . Adjusted survival rates were 91 % for PCR and 69 % for SW ( p = 0.004 ) . These results suggest that there is no need to re-open a cavity and perform a second excavation for pulp vitality to be preserved ( Clinical trials registration NCT00887952 ) OBJECTIVE This study aim ed to evaluate the progression of sealed non-cavitated dentinal occlusal caries in a r and omised controlled clinical trial . MATERIAL S AND METHODS Sixty teeth with non-cavitated dentinal occlusal caries were selected in patients with a high risk for caries . Patients were r and omly divided into two groups so that each group included 30 teeth . Patients in the experiment group were given oral hygiene instructions and a fissure sealant . Patients in the control group were given oral hygiene instructions only . Caries progression and sealant loss were monitored over a period of 36 months by clinical and radiographic examinations . RESULTS Clinical and radiographic progression of caries was significantly more frequent in the control group than in the experiment group . Three teeth lost their sealant and showed caries progression , but this was apparent only at the 12-month follow-up . At the 24- and 36-month recall appointments , neither sealant loss nor caries progression were observed . CONCLUSION The pit and fissure sealant utilised in this study was shown to be effective in arresting carious lesions at 36 months The aim was to assess the prevalence of pulp exposure after stepwise versus direct complete excavation of permanent posterior teeth with deep carious lesions . The material , representing 116 patients aged 6 - 16 yrs ( mean = 10.2 yrs ) , consisted of 127 teeth with radiographs revealing carious lesions to such a depth that pulp exposure could be expected if direct complete excavation was performed . Teeth with clinical symptoms , other than transient pain shortly before treatment , were not accepted . The teeth were r and omly selected for either treatment procedure . Stepwise excavation implied removal of the bulk of carious tissue and application of calcium hydroxide , followed by sealing of the cavity with zinc-oxide eugenol cement . After a period of 8 - 24 weeks the rest of the carious dentin was removed and the cavity sealed with calcium hydroxide , zinc-oxide-eugenol ( ZOE ) and a restorative material . Direct complete excavation entailed removal of all carious dentin followed by sealing as mentioned above . In case of pulp exposure , pulp treatment was performed . The pulp was exposed in 40 of the teeth treated by direct complete excavation . The corresponding figure for those treated by stepwise excavation was 17.5 % . The difference was statistically significant . The teeth with no pulp exposure after direct or stepwise excavation showed normal clinical and radiographic conditions at the last check-up ( mean = 43 months ) PURPOSE The purpose of this study was to examine whether 1- or 2-visit indirect pulp therapy ( IPT ) is more successful and to determine if the operator can successfully decide when to stop removing caries without exposing the pulp . METHODS A total of 154 teeth ( 94 primary second molars and 60 young permanent first molars ) were included in the study from a total of 123 4- to 15-year-old patients . The teeth had deep carious lesions but lacked the preoperative signs and symptoms of irreversible pulpitis . The teeth were r and omly selected and treated either with 1-visit IPT , 2-visit IPT , or direct complete excavation ( DCE ) . Follow-up examinations were conducted on the teeth over 1 year at 3-month intervals . RESULTS The pulp was exposed in 12 teeth ( 22 % ) treated by DCE , whereas 3 teeth ( 6 % ) were treated by 1-visit IPT and 4 teeth ( 8 % ) with 2-visit IPT . A statistically significant difference was found between IPT and DCE groups in terms of pulp exposure ( P<.05 ) . The teeth without pulp exposure showed normal clinical and radiographic conditions during the 1-year follow-up , except for 3 primary teeth . CONCLUSIONS Indirect pulp therapy in both primary and young permanent teeth can be used successfully with a 1- or 2-visit approach This study assessed the efficacy of sealing proximal lesions on adult patients using a split-mouth design . Eighty-two 15- to 39-year-olds from the Dental Faculties in Copenhagen and Bogotá participated , each having 2 or more proximal lesions in the following radiographic stages : ( 1 ) lesion restricted to the outer half of enamel ; ( 2 ) lesion from the inner half of enamel including the enamel dentine junction , and ( 3 ) lesion restricted to the outer third of dentine . St and ardized geometrically aligned baseline and follow-up radiographs were obtained . One r and omly selected lesion ( test ) in each patient was sealed with 1 of 2 resins . The patients were instructed to floss all the proximal lesions 3 times per week . The baseline to 18 months difference in caries lesion progression status was assessed using 3 methods : ( 1 ) radiographs were independently assessed visually ; ( 2 ) radiographs were read in pairs , and ( 3 ) using subtraction radiography of digitized images . A total of 72 subjects finished the study ( 12.2 % dropout ) . The compliance concerning flossing was poor ( 15 % ) . For the repeated examinations kappa was 0.84 for the visual examination , 0.44 for the paired readings and 0.84 for the subtraction examination . Two test lesions and 1 control lesion were restored . For the independent radiograph assessment method 10 and 26 % progressed in the test and control group , respectively ( p > 0.05 ) ; with the paired radiograph method the corresponding data were 22 % in the test and 47 % in the control groups ( p < 0.01 ) . By subtraction radiography 44 % of the test group and 84 % of the control were judged to have progressed ( p < 0.001 ) . The sealing technique was superior to instructing patients to floss , and subtraction radiography appeared to be the most sensitive method for assessing lesion progression A pragmatic r and omised controlled trial comparing a minimally invasive approach based on atraumatic restorative treatment ( ART ) procedures ( test ) was tested against the st and ard-care approach ( control ) to treat early childhood caries ( ECC ) in a primary -care setting in Perth , W.A. , Australia . Parent/child dyads with ECC were allocated to the test or control group using stratified block r and omisation . Children were examined at baseline and follow-up by two calibrated examiners blinded to group allocation status . Dental therapists trained in ART provided treatment to the test group and dentists treated the control group . Restoration quality was evaluated at follow-up using the ART criteria . Data were analysed on an intention-to-treat basis ; test of proportions , Wilcoxon rank test and logistic regression , controlling for clustering of teeth , were used . Two hundred and fifty-four children were r and omised ( test = 127 and control = 127 ) . There was no statistically significant difference in age , sex and baseline caries experience between the test and control groups . At follow-up ( mean interval 11.4 months , SD 3.1 ) , 220 children were examined ( test = 115 and control = 105 ) and 597 teeth ( test = 417 and control = 180 ) were evaluated for restoration quality , of which 16.8 % ( test ) and 6.7 % ( control ) were judged to have failed ( required replacement ; p < 0.01 ) . Intention-to-treat , multiple logistic regression found multisurface restorations ( OR = 10.4 ) had significantly higher odds of failure , while referral for specialist paediatric care had significantly lower odds of restoration failure ( OR = 0.2 ) . The ART-based approach enabled more children and teeth to be treated , and multisurface restoration and treatment in a primary -care setting had higher odds of restoration failure PURPOSE To evaluate clinical and radiographic outcomes of indirect pulp treatment ( IPT ) in primary molars after long-term function ( up to 60 months ) . METHODS Teeth with deep carious lesions without signs and symptoms of irreversible pulpitis were divided by r and om allocation into two groups , according to the capping material utilized over demineralized dentin : experimental group ( 1 ) : self-etching adhesive system ( Clearfil SE Bond ) ; and control group ( 2 ) : calcium hydroxide liner ( Dycal ) . Both groups were filled with resin composite ( Z250 ) and su bmi tted to a clinical and radiographic monitoring period until exfoliation . RESULTS After the follow-up period ( up to 60 months ) , no statistical difference was found between groups ( P= 0.514 ) . The overall success rate reached 78 % . The failures occurred after the first year period recall Compared with a step-by-step procedure , the one-step excavation of deep carious lesions in primary molars proved to be the treatment of choice in a clinical ly , microbiologically and histologically controlled trial . The stepwise method failed to produce any significant reduction in pulp exposure . Sensitivity assessment and percussion findings did not result in a reliable and unambiguous evaluation of treatment success . Histology showed inflammation-free pulps in 67 % of the deciduous molars irrespective of the treatment method used . Microbiological examination revealed slightly softened dentin to be significantly more infected than clinical ly acceptable , hard dentin ; although only 59.3 % of the cavity floors were free of microorganisms . Chronic pulp inflammations were correlated with the presence of streptococci and lactobacilli , whereas actinomycetes were associated with inflammation-free pulps Aim : To compare 24-month pulp health outcomes of partial caries removal ( PCR ) and total caries removal ( TCR ) with composite restoration in primary molars . Methods : 48 children aged 3 - 8 years with at least one molar with a deep carious lesion were included . 120 teeth were r and omized to control ( TCR ; n = 54 ; 69 % class II ) and test ( PCR ; n = 66 ; 63 % class II ) groups . Total absence of carious tissue was confirmed using a blunt-tipped probe in the TCR group . For PCR , excavation was stopped when hardened , dried dentin with a leathery consistency was achieved . Pulpotomy was performed in cases of pulp exposure . Results : Pulp exposure occurred in 2 and 27.5 % of teeth treated with PCR and TCR , respectively ( p < 0.01 ) . The operative time was significantly higher for TCR than PCR . Success rates were 92 and 96 % in the PCR and TCR groups , respectively ( p = 0.34 ) . The success rate tended to be lower in occlusoproximal ( 92 % ) than in occlusal ( 100 % ) lesions ( p = 0.08 ) . Conclusion : The clinical and radiographic success rates of PCR and TCR in primary teeth with deep carious lesions were high and did not differ significantly , indicating that PCR is a reliable minimally invasive approach in primary teeth and that the retention of carious dentin does not interfere with pulp vitality . Moreover , PCR provided other clinical ly relevant advantages over TCR , especially lower incidence of pulp exposure and lower operative time In this study , 1,325 school children from 7 farm schools were examined . Their mean age ( + /- SD ) was 10.5 + /- 3.0 ( range 6 - 11 ) years . At baseline , the mean DMFT score was 1.1 + /- 1.7 and 36.4 % of the children had caries . The prevalence of fluorosis among the children was 12.6 % . Curative treatment was offered to all the children . A total of 113 children ( 8.5 % ) with one-surface cavities on permanent teeth and without fluorosis were treated using the atraumatic restorative treatment ( ART ) approach . A total number of 163 cavities were included in the study , of which 82 were treated with Fuji IX glass-ionomer cement and 81 with Ketac-MOLAR ( h and mix ) . One year after treatment , restoration and sealant parts of ART fillings were examined . Caries status was also determined . The placing of the ART fillings and their evaluation were performed by different practitioners . A total number of 108 restorations ( 58 with Fuji IX , 50 with Ketac-MOLAR ) were evaluated . Results of ART fillings showed a survival rate of 93.1 % with Fuji and 94.0 % with Ketac-MOLAR . Retention of the sealant parts of ART fillings was observed in 81 % of restorations with Fuji IX and 76 % with Ketac-MOLAR , not connected to the filled cavity . Caries was absent on all teeth restored with Fuji IX and noted in only one tooth restored with Ketac-MOLAR , not connected to the filled cavity . The retention rate after a 12-month period was acceptable and ART approach proved to be an appropriate technique for restoring teeth in this population group . There were no statistically significant differences between the survival rates of the two glass-ionomer restorative material s ( P > 0.05 ) Since viable bacteria can persist in tooth cavities regardless of the technique used for caries removal , the objective of the present r and omized clinical trial was to examine the microflora of primary teeth treated by complete or partial removal of carious dentin . Deciduous molars with acute carious lesions in the inner half of dentin and vital pulp were r and omly divided into two groups of 16 : complete removal , in which the carious dentin was completely removed with the help of a caries detector dye , and partial removal , in which the carious dentin was completely removed from the dentinoenamel junction and lateral walls , while the necrotic carious dentin from the cavity floor was only removed superficially . Dentin sample s were obtained with a sterile No. 3 bur after caries removal and 3–6 months after protection with calcium hydroxide cement and restoration of the cavities with resin composite . The sample s were stored in thioglycolate . Decimal dilutions were then prepared and seeded for the enumeration of Streptococcus spp . , mutans streptococci , Lactobacillus spp . and total microorganisms . Before sealing , a larger number of microorganisms was detected in teeth su bmi tted to partial caries removal compared to the complete removal group . However , after sealing the level of colonization was similar in the two groups for all microorganisms studied . The results suggest that persistence of bacteria does not seem to be a reason for reopening of cavities in deciduous teeth after partial caries removal |
1,662 | 30,060,590 | Findings support associations between several components of motor proficiency and academic performance in mathematics and reading .
There was evidence that fine motor proficiency was significantly and positively associated with academic performance in mathematics and reading , particularly during the early years of school .
Significant positive associations were also evident between academic performance and components of gross motor proficiency , specifically speed and agility , upper-limb coordination , and total gross motor scores .
Preliminary evidence from a small number of experimental studies suggests motor skill interventions in primary school setting s may have a positive impact on academic performance in mathematics and /or reading . | Positive associations exist between physical activity , cognition , and academic performance in children and adolescents .
Further research is required to examine which factors underpin the relationships between physical activity and academic performance .
This systematic review aim ed to identify , critically appraise , and synthesize findings of studies examining relationships between motor proficiency and academic performance in mathematics and reading in typically developing school-aged children and adolescents . | Objective : An emerging field of research indicates that physical activity can benefit cognitive functions and academic achievements in children . However , less is known about how academic achievements can benefit from specific types of motor activities ( e.g. , fine and gross ) integrated into learning activities . Thus , the aim of this study was to investigate whether fine or gross motor activity integrated into math lessons ( i.e. , motor-enrichment ) could improve children 's mathematical performance . Methods : A 6-week within school cluster-r and omized intervention study investigated the effects of motor-enriched mathematical teaching in Danish preadolescent children ( n = 165 , age = 7.5 ± 0.02 years ) . Three groups were included : a control group ( CON ) , which received non-motor enriched conventional mathematical teaching , a fine motor math group ( FMM ) and a gross motor math group ( GMM ) , which received mathematical teaching enriched with fine and gross motor activity , respectively . The children were tested before ( T0 ) , immediately after ( T1 ) and 8 weeks after the intervention ( T2 ) . A st and ardized mathematical test ( 50 tasks ) was used to evaluate mathematical performance . Furthermore , it was investigated whether motor-enriched math was accompanied by different effects in low and normal math performers . Additionally , the study investigated the potential contribution of cognitive functions and motor skills on mathematical performance . Results : All groups improved their mathematical performance from T0 to T1 . However , from T0 to T1 , the improvement was significantly greater in GMM compared to FMM ( 1.87 ± 0.71 correct answers ) ( p = 0.02 ) . At T2 no significant differences in mathematical performance were observed . A subgroup analysis revealed that normal math-performers benefitted from GMM compared to both CON 1.78 ± 0.73 correct answers ( p = 0.04 ) and FMM 2.14 ± 0.72 correct answers ( p = 0.008 ) . These effects were not observed in low math-performers . The effects were partly accounted for by visuo-spatial short-term memory and gross motor skills . Conclusion : The study demonstrates that motor enriched learning activities can improve mathematical performance . In normal math performers GMM led to larger improvements than FMM and CON . This was not the case for the low math performers . Future studies should further eluci date the neurophysiological mechanisms underlying the observed behavioral effects The aim was to study long-term effects on motor skills and school performance of increased physical education ( PE ) . All pupils born 1990 - 1992 from one school were included in a longitudinal study over nine years . An intervention group ( n = 129 ) achieved daily PE ( 5 × 45 min/week ) and if needed one extra lesson of adapted motor training . The control group ( n = 91 ) had PE two lessons/week . Motor skills were evaluated by the Motor Skills Development as Ground for Learning observation checklist and school achievements by marks in Swedish , English , Mathematics , and PE and proportion of pupils who qualified for upper secondary school . In school year 9 there were motor skills deficits in 7 % of pupils in the intervention group compared to 47 % in the control group ( P < 0.001 ) , 96 % of the pupils in the intervention group compared to 89 % in the control group ( P < 0.05 ) qualified for upper secondary school . The sum of evaluated marks was higher among boys in the intervention group than in the control group ( P < 0.05 ) . The sum of marks was also higher in pupils with no motor skills deficit than among pupils with motor skills deficits ( P < 0.01 ) , as was the proportion of pupils who qualified for upper secondary school ( 97 % vs 81 % , P < 0.001 ) . Daily PE and adapted motor skills training during the compulsory school years is a feasible way to improve not only motor skills but also school performance and the proportion of pupils who qualify for upper secondary school BACKGROUND Perceptual-motor skills contribute to a variety of basic learning skills associated with normal academic success . This study aim ed to determine the relationship between academic performance and perceptual-motor skills in first grade South African learners and whether low SES ( socio-economic status ) school type plays a role in such a relationship . METHODS This cross-sectional study of the baseline measurements of the NW-CHILD longitudinal study included a stratified r and om sample of first grade learners ( n = 812 ; 418 boys and 394 boys ) , with a mean age of 6.78 years ± 0.49 living in the North West Province ( NW ) of South Africa . The Beery-Buktenica Developmental Test of Visual-Motor Integration-4 ( VMI ) was used to assess visual-motor integration , visual perception and h and control while the Bruininks Oseretsky Test of Motor Proficiency , short form ( BOT2-SF ) assessed overall motor proficiency . Academic performance in math , reading and writing was assessed with the Mastery of Basic Learning Areas Question naire . Linear mixed models analysis was performed with spss to determine possible differences between the different VMI and BOT2-SF st and ard scores in different math , reading and writing mastery categories ranging from no mastery to outst and ing mastery . A multinomial multilevel logistic regression analysis was performed to assess the relationship between a clustered score of academic performance and the different determinants . RESULTS A strong relationship was established between academic performance and VMI , visual perception , h and control and motor proficiency with a significant relationship between a clustered academic performance score , visual-motor integration and visual perception . A negative association was established between low SES school types on academic performance , with a common perceptual motor foundation shared by all basic learning areas . CONCLUSION Visual-motor integration , visual perception , h and control and motor proficiency are closely related to basic academic skills required in the first formal school year , especially among learners in low SES type schools Changes in cognitive function induced by physical activity have been proposed as a mechanism for the link between physical activity and academic performance . The aim of this study was to investigate if executive function mediated the prospect i ve relations between indices of physical activity and academic performance in a sample of 10-year-old Norwegian children . The study included 1,129 children participating in the Active Smarter Kids ( ASK ) trial , followed over 7 months . Structural equation modeling ( SEM ) with a latent variable of executive function ( measuring inhibition , working memory , and cognitive flexibility ) was used in the analyses . Predictors were objective ly measured physical activity , time spent sedentary , aerobic fitness , and motor skills . Outcomes were performance on national tests of numeracy , reading , and English ( as a second language ) . Generally , indices of physical activity did not predict executive function and academic performance . A modest mediation effect of executive function was observed for the relation between motor skills and academic performance . Trial registration : Clinical trials.gov registry , trial registration number : NCT02132494 BACKGROUND Physical Activity Across the Curriculum ( PAAC ) was a three-year cluster r and omized controlled trial to promote physical activity and diminish increases in overweight and obesity in elementary school children . METHODS Twenty-four elementary schools were cluster r and omized to the Physical Activity Across the Curriculum intervention or served as control . All children in grade s two and three were followed to grade s four and five . Physical Activity Across the Curriculum promoted 90 min/wk of moderate to vigorous intensity physically active academic lessons delivered by classroom teachers . Body Mass Index was the primary outcome , daily Physical activity and academic achievement were secondary outcomes . RESULTS The three-year change in Body Mass Index for Physical Activity Across the Curriculum was 2.0+/-1.9 and control 1.9+/-1.9 , respectively ( NS ) . However , change in Body Mass Index from baseline to 3 years was significantly influenced by exposure to Physical Activity Across the Curriculum . Schools with > or = 75 min of Physical Activity Across the Curriculum/wk showed significantly less increase in Body Mass Index at 3 years compared to schools that had < 75 min of Physical Activity Across the Curriculum ( 1.8+/-1.8 vs. 2.4+/-2.0 , p=0.02 ) . Physical Activity Across the Curriculum schools had significantly greater changes in daily Physical activity and academic achievement scores . CONCLUSIONS The Physical Activity Across the Curriculum approach may promote daily Physical activity and academic achievement in elementary school children . Additionally , 75 min of Physical Activity Across the Curriculum activities may attenuate increases in Body Mass Index We first replicated the data analytic strategy used in Duncan et al. ( 2007 ) with a population -based data set of French-speaking children from Quebec ( Canada ) . Prospect i ve associations were examined between cognitive , attention , and socioemotional characteristics underlying kindergarten school readiness and second grade math , reading , and general achievement . We then extended this school readiness model by including motor skills as an additional element in the prediction equation and exp and ed the original strategy by including classroom engagement . The Montreal Longitudinal-Experimental Preschool Study , featured in Duncan et al. , served as the Canadian reference group . In the replication model , kindergarten cognitive and attention characteristics predicted achievement by the end of 2nd grade . Although inconsistent across outcomes , behavioral problems and skills also emerged as predictors of some aspects of later achievement . Coefficients for kindergarten math skills were largest , followed by attention skills , receptive language skills , attention problems , and behavior . Most coefficients resembled those generated in the initial study . In our extension model , fine motor skills added their significant contribution to the prediction of later achievement above and beyond the original key elements of school readiness . Our extension model confirmed prospect ively associations between kindergarten cognitive , attention , fine motor , and physical aggression characteristics and later achievement and classroom engagement by the end of 2nd grade . Although they comparatively showed better long-term benefits from stronger early attention skills , girls with less kindergarten cognitive skills were more vulnerable than boys with similar deficits when predicting 2nd grade math OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity PURPOSE The purpose of this study was twofold : 1 ) to evaluate the effectiveness of a school-based physical activity intervention , Action Schools ! BC ( AS ! BC ) , for maintaining academic performance in a multiethnic group of elementary children , and 2 ) to determine whether boys and girls ' academic performance changed similarly after participation in AS ! BC . METHODS This was a 16-month cluster r and omized controlled trial . Ten schools were r and omized to intervention ( INT ) or usual practice ( UP ) . One INT school administered the wrong final test , and one UP school grade d their own test , so both were excluded . Thus , eight schools ( six INT , two UP ) were included in the final analysis . Children ( 143 boys , 144 girls ) in grade s 4 and 5 were recruited for the study . We used the Canadian Achievement Test ( CAT-3 ) to evaluate academic performance ( TotScore ) . Weekly teacher activity logs determined amounts of physical activity delivered by teachers to students . Physical activity was determined with the Physical Activity Question naire for Children ( PAQ-C ) . Independent t-tests compared descriptive variables between groups and between boys and girls . We used a mixed linear model to evaluate differences in TotScore at follow-up between groups and between girls and boys . RESULTS Physical activity delivered by teachers to children in INT schools was increased by 47 min x wk(-1 ) ( 139 + /- 62 vs 92 + /- 45 , P < 0.001 ) . Participants attending UP schools had significantly higher baseline TotScores than those attending INT schools . Despite this , there was no significant difference in TotScore between groups at follow-up and between boys and girls at baseline and follow-up . CONCLUSION The AS ! BC model is an attractive and feasible intervention to increase physical activity for students while maintaining levels of academic performance This pilot study examined the influence of participation in a 6-week bimanual coordination program on Grade 5 students ' reading achievement . Twenty Grade 5 students participated in a bimanual activity ( sport stacking ) and were tested whether reading achievement scores were significantly different from the scores for 21 control students . The experimental group consisted of 20 students ( 11 boys , 9 girls ) from one intact classroom cohort ; the control group consisted of 21 students ( 12 boys , 9 girls ) from one intact classroom cohort . Students in both groups ranged in age from 10 to 11 years . The intact classroom cohorts were r and omly assigned to experimental and control groups . Reading achievement was measured by differences in pre- and posttest scores from the GMRT-4 Decoding and Comprehension skill subtests . Group by sex analyses of covariance , using pretest scores as covariates , indicated that there were no significant differences by group or sex for decoding skills . A significant increase was found for the experimental group on Comprehension skills . Therefore , participation in a bimanual coordination program , using sport stacking as the activity , may improve Grade 5 students ' reading comprehension skills , regardless of sex The Spinal Cord Injury Rehabilitation Evidence ( SCIRE ) is a synthesis of the research evidence underlying rehabilitation interventions to improve the health of people living with SCI . SCIRE covers a comprehensive set of topics and in this issue we present six papers relevant to SCI rehabilitation clinicians ( SCI inpatient rehabilitation practice s , gait strategies , upper extremity reconstructive surgery , spasticity treatments , cardiovascular health and bone health ) . The SCIRE used a systematic and well-defined protocol to assess and synthesize the evidence . Each article was scored for its method ological quality using either the Physiotherapy Evidence Data base ( PEDro ) Score for r and omized controlled trials or the Downs and Black Tool for other types of studies . Following the individual study assessment , conclusions were drawn about the accumulated studies for each topic of interest based on the levels of evidence , quality of studies and concurring evidence . The SCIRE project was design ed for health professionals to inform them of best practice To analyze the effects of an intervention focused on increasing the time and intensity of Physical Education ( PE ) , on adolescents ' cognitive performance and academic achievement . A 4-month group-r and omized controlled trial was conducted in 67 adolescents from South-East Spain , 2007 . Three classes were r and omly allocated into control group ( CG ) , experimental group 1 ( EG1 ) and experimental group 2 ( EG2 ) . CG received usual PE ( two sessions/week ) , EG1 received four PE sessions/week and EG2 received four PE sessions/week of high intensity . Cognitive performance ( non-verbal and verbal ability , abstract reasoning , spatial ability , verbal reasoning and numerical ability ) was assessed by the Spanish Overall and Factorial Intelligence Test , and academic achievement by school grade s. All the cognitive performance variables , except verbal reasoning , increased more in EG2 than in CG ( all P < 0.05 ) . Average school grade s ( e.g. , mathematics ) increased more in EG2 than in CG . Overall , EG2 improved more than EG1 , without differences between EG1 and CG . Increased PE can benefit cognitive performance and academic achievement . This study contributes to the current knowledge by suggesting that the intensity of PE sessions might play a role in the positive effect of physical activity on cognition and academic success . Future studies involving larger sample sizes should confirm or contrast these preliminary findings |
1,663 | 28,393,659 | Several factors ( e.g. , caffeine , aging , and blood gases ) were found to induce a considerable effect on brain perfusion that was consistent across different studies ; for other factors , the modifying effect was found to be debatable , due to contradictory results or lack of evidence . | Quantitative measurements of brain perfusion are influenced by perfusion-modifiers .
St and ardization of measurement conditions and correction for important modifiers is essential to improve accuracy and to facilitate the interpretation of perfusion-derived parameters . | Brain temperature appears to be an important factor affecting motor activity , but it is not known to what extent brain temperature increases during prolonged exercise in humans . Cerebral heat exchange was therefore evaluated in seven males during exercise with and without hyperthermia . Middle cerebral artery mean blood velocity ( MCA V(mean ) ) was continuously monitored while global cerebral blood flow ( CBF ) and cerebral energy turnover were determined at the end of the two exercise trials in three subjects . The arterial to venous temperature difference across the brain ( v-aD(temp ) ) was determined via thermocouples placed in the internal jugular vein and in the aorta . The jugular venous blood temperature was always higher than that of the arterial blood , demonstrating that heat was released via the CBF during the normothermic as well as the hyperthermic exercise condition . However , heat removal via the jugular venous blood was 30 + /- 6 % lower during hyperthermia compared to the control trial . The reduced heat removal from the brain was mainly a result of a 20 + /- 6 % lower CBF ( 22 + /- 9 % reduction in MCA V(mean ) ) , because the v-aD(temp ) was not significantly different in the hyperthermic ( 0.20 + /- 0.05 degrees C ) compared to the control trial ( 0.22 + /- 0.05 degrees C ) . During hyperthermia , the impaired heat removal via the blood was combined with a 7 + /- 2 % higher heat production in the brain and heat was consequently stored in the brain at a rate of 0.20 + /- 0.06 J g(-1 ) min(-1 ) . The present results indicate that the average brain temperature is at least 0.2 degrees C higher than that of the body core during exercise with or without hyperthermia The effects of naltrexone-precipitated withdrawal from buprenorphine on behavior and regional cerebral blood flow ( rCBF ) were studied in 11 opiate-dependent patients . Patients initially received buprenorphine , 2 mg sublingually , every day for 7 days . They were then challenged sequentially with placebo and naltrexone , 25 mg orally , before single photon emission computed tomography with technetium-99m-d , l-hexamethyl-propylene amine oxime as tracer . Behavioral ratings of withdrawal severity were made before and after naltrexone/placebo administration . Naltrexone produced significantly greater signs and symptoms of opiate withdrawal than placebo . Analysis of variance revealed no significant regionally specific effect of naltrexone on rCBF ratios . Severity of withdrawal , however , showed a significant negative correlation with rCBF in the anterior cingulate cortex following naltrexone . These results are interesting as the anterior cingulate region has been implicated in the emotional component of pain and in opiate-induced analgesia In a prospect i ve study of the natural development of total cerebral blood flow volume ( CBFV ) , the common , external and internal carotid and vertebral arteries were examined in 94 healthy children and adolescents between 3 and 18 years of age ( sex and age evenly distributed ) using a 7.0-MHz transducer of a computed sonography system . Intravascular flow volumes were calculated with the product of angle-corrected time-averaged flow velocity and the cross-sectional area of the vessel . CBFV was determined as the sum of flow volumes in the internal carotid and vertebral arteries of both sides . CBFV increased significantly between 3 and 6.5 years of age ( from 687 ± 85 to 896 ± 110 ml/min ; age correlation , p ≤ 0.01 ) and declined thereafter ( p ≤ 0.001 ) to a constant level of ∼700 ml/min at 15 years of age . There was no difference in CBFV between sexes . The proportion of bilateral vertebral artery flow volume in total CBFV decreased significantly between the ages of 3 and 18 years ( p ≤ 0.001 ) . As the flow volumes of the external carotid arteries increased markedly from childhood to adulthood , flow volumes of the common carotid arteries were not representative of CBFV . Intrasession test-retest correlation of CBFV was high ( r = 0.89 , p ≤ 0.0001 ) . Reference data for the childhood years presented here and previously described results from healthy adults allow us to outline the natural evolution of CBFV in humans . The reliability of the method has already been demonstrated . Thus , it may now be introduced into clinical application The effects of intravenous amphetamine infusion ( 0.3 mg/kg ) on cerebral blood flow ( CBF ) and measures of autonomic and behavioral arousal were studied in 12 normal male volunteers in a placebo-controlled crossover design . Nonsignificant decreases were seen in CBF ( measured by 133Xe inhalation ) , despite significant increases in autonomic and behavioral arousal . The apparent dissociation of CBF and arousal appears to be compatible with other human experiments suggesting that amphetamine decreases CBF and metabolism , as well as with neurobiological findings on the effects of catecholamines on resting cortical activity and mechanisms of increased attention . The results differ substantially , however , from findings of increased CBF and metabolism in animals . Although the larger doses used in animals most likely explain the discrepancy , technical limitations in human brain imaging can not be excluded Reduced cerebral perfusion may contribute to the development of cerebrovascular and neurodegenerative diseases . Little is known on cerebral perfusion in the general population , as most measurement techniques are too invasive for application in large groups of healthy individuals . Total cerebral blood flow ( tCBF ) can be noninvasively measured by magnetic resonance imaging ( MRI ) but is highly correlated with brain volume . We calculated total brain perfusion by dividing tCBF by brain volume , and we investigated determinants of total brain perfusion in comparison with tCBF . Secondly , we studied whether persons with a low tCBF or low total brain perfusion have a larger volume of white matter lesions ( WML ) . This study is based on 892 persons aged 60 to 91 years from the Rotterdam Study , a population -based cohort study . We performed two-dimensional ( 2D ) phase-contrast MRI for tCBF measurement . Brain volume and WML volume were quantitatively assessed . Cardiovascular determinants were assessed by interview and physical examination . We assessed associations between cardiovascular determinants and flow measures with linear regression models , adjusted for age and sex . Associations between tCBF or total brain perfusion and WML volume were assessed using general linear models . We found that determinants of tCBF and total brain perfusion differed largely due to the large influence of brain volume on tCBF values . Persons with low total brain perfusion had a significantly larger WML volume compared with those with high total brain perfusion . Prospect i ve studies are required to unravel whether hypoperfusion contributes to WML formation or that tissue damage , manifested by WML , leads to brain hypoperfusion Regional cerebral blood flow ( rCBF ) was studied in 60 elderly persons ( aged 65 to 84 years ) recruited from a population -based study , with single photon emission computed tomography using technetium 99m-labeled hexamethylpropylene amine oxime . We investigated whether it is only age that affects rCBF or whether other factors can be indentified that explain this relationship . Using multiple linear regression analysis , increasing age was significantly associated with rCBF decrease in parietal , temporo-parietal , and temporal cortex , but not in frontal cortex . Adjustment with several risk factors for cerebrovascular disease , including hypertension , history of myocardial infa rct ion , factor VIIc , factor VIIIc , cholesterol and HDL cholesterol , smoking , and diabetes mellitus had no influence on these relations . Conversely , the association between age and rCBF was no longer statistically significant after adjustment with fibrinogen and indicators of carotid atherosclerosis , including intima-media wall thickness of the carotid artery and plaques in the carotid artery . Correction with local ratings of cortical atrophy did not affect the relations between age and rCBF . The results suggest that in the elderly population rCBF declines with age in posterior cortical areas and that these changes may well be explained by the presence of atherosclerosis . Reduced contractility of the vascular muscle wall with increasing age result ing from atherosclerosis may be the underlying mechanism Objectives : To explore relationships between scuba diving activity , brain , and behaviour , and more specifically between global cerebral blood flow ( CBF ) or cognitive performance and total , annual , or last 6 months ’ frequencies , for st and ard dives or dives performed below 40 m , in cold water or warm sea geographical environments . Methods : A prospect i ve cohort study was used to examine divers from diving clubs around Lac Léman and Geneva University Hospital . The subjects were 215 healthy recreational divers ( diving with self-contained underwater breathing apparatus ) . Main outcome measures were : measurement of global CBF by 133Xe SPECT ( single photon emission computed tomography ) ; psychometric and neuropsychological tests to assess perceptual-motor abilities , spatial discrimination , attentional re sources , executive functioning , and memory ; evaluation of scuba diving activity by question naire focusing on number and maximum depth of dives and geographical site of the diving activity ( cold water v warm water ) ; and body composition analyses ( BMI ) . Results : ( 1 ) A negative influence of depth of dives on CBF and its combined effect with BMI and age was found . ( 2 ) A specific diving environment ( more than 80 % of dives in lakes ) had a negative effect on CBF . ( 3 ) Depth and number of dives had a negative influence on cognitive performance ( speed , flexibility and inhibition processing in attentional tasks ) . ( 4 ) A negative effect of a specific diving environment on cognitive performance ( flexibility and inhibition components ) was found . Conclusions : Scuba diving may have long-term negative neurofunctional effects when performed in extreme conditions , namely cold water , with more than 100 dives per year , and maximal depth below 40 Mobile phone use has increased worldwide but its possible effects on the brain remain unclear . The aim of the present study was to investigate the effect of acute exposure to a radio frequency electromagnetic field ( RF EMF ) generated by a mobile phone operating in the Global System for Mobile Communication ( GSM ) 900 MHz on cerebral blood flow . Twenty-nine volunteers attended two experimental sessions : a sham exposure session and a real exposure session in a cross-over double-blind study in which a mobile phone was positioned on the left side of the head . In one session , the mobile phone was operated without RF radiation ( sham phone ) and in the other study it was operated with RF radiation ( real phone ) for 20 min . Thus , each subject served as its own control . Middle cerebral artery blood flow was monitored noninvasively by transcranial Doppler sonography to measure middle cerebral artery blood flow velocity . Pulsatility index and resistance index were also evaluated . A voluntary breath holding physiological test was carried out as a positive control for testing cerebral vasoreactivity . Hemodynamic variables were recorded and analyzed before , during and after mobile phone exposure . No significant changes were detected in studied variables in middle cerebral arteries during sham or real exposure . In the exposed side the cerebral blood flow velocity , the pulsatility index and the resistance index during sham and real exposure were respectively : [ 61.9 ± 1.3 , 61.7 ± 1.3 cm/s ( P = 0.89 ) ] ; [ 0.93 ± 0.03 , 0.90 ± 0.02 ( P = 0.84 ) ] and [ 0.58 ± 0.01 , 0.58 ± 0.01 ( P = 0.96 ) ] at baseline ; and [ 60.6 ± 1.3 , 62 ± 1.6 cm/s ( P = 0.40 ) ] ; [ 0.91 ± 0.03 , 0.87 ± 0.03 ( P = 0.97 ) ] ; [ 0.57 ± 0.01 , 0.56 ± 0.01 ( P = 0.82 ) ] after 20 min of exposure . Twenty minutes of RF exposure to a mobile phone does not seem to affect the cerebral circulation Psychedelic drugs have a long history of use in healing ceremonies , but despite renewed interest in their therapeutic potential , we continue to know very little about how they work in the brain . Here we used psilocybin , a classic psychedelic found in magic mushrooms , and a task-free functional MRI ( fMRI ) protocol design ed to capture the transition from normal waking consciousness to the psychedelic state . Arterial spin labeling perfusion and blood-oxygen level-dependent ( BOLD ) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin . Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD . As predicted , profound changes in consciousness were observed after psilocybin , but surprisingly , only decreases in cerebral blood flow and BOLD signal were seen , and these were maximal in hub regions , such as the thalamus and anterior and posterior cingulate cortex ( ACC and PCC ) . Decreased activity in the ACC/medial prefrontal cortex ( mPFC ) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects . Based on these results , a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed . Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC . These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain 's key connector hubs , enabling a state of unconstrained cognition IMPORTANCE Increases in fructose consumption have paralleled the increasing prevalence of obesity , and high-fructose diets are thought to promote weight gain and insulin resistance . Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion , and central administration of fructose provokes feeding in rodents , whereas central ly administered glucose promotes satiety . OBJECTIVE To study neurophysiological factors that might underlie associations between fructose consumption and weight gain . DESIGN , SETTING , AND PARTICIPANTS Twenty healthy adult volunteers underwent 2 magnetic resonance imaging sessions at Yale University in conjunction with fructose or glucose drink ingestion in a blinded , r and om-order , crossover design . MAIN OUTCOME MEASURES Relative changes in hypothalamic regional cerebral blood flow ( CBF ) after glucose or fructose ingestion . Secondary outcomes included whole-brain analyses to explore regional CBF changes , functional connectivity analysis to investigate correlations between the hypothalamus and other brain region responses , and hormone responses to fructose and glucose ingestion . RESULTS There was a significantly greater reduction in hypothalamic CBF after glucose vs fructose ingestion ( -5.45 vs 2.84 mL/g per minute , respectively ; mean difference , 8.3 mL/g per minute [ 95 % CI of mean difference , 1.87 - 14.70 ] ; P = .01 ) . Glucose ingestion ( compared with baseline ) increased functional connectivity between the hypothalamus and the thalamus and striatum . Fructose increased connectivity between the hypothalamus and thalamus but not the striatum . Regional CBF within the hypothalamus , thalamus , insula , anterior cingulate , and striatum ( appetite and reward regions ) was reduced after glucose ingestion compared with baseline ( P < .05 significance threshold , family-wise error [ FWE ] whole-brain corrected ) . In contrast , fructose reduced regional CBF in the thalamus , hippocampus , posterior cingulate cortex , fusiform , and visual cortex ( P < .05 significance threshold , FWE whole-brain corrected ) . In whole-brain voxel-level analyses , there were no significant differences between direct comparisons of fructose vs glucose sessions following correction for multiple comparisons . Fructose vs glucose ingestion result ed in lower peak levels of serum glucose ( mean difference , 41.0 mg/dL [ 95 % CI , 27.7 - 54.5 ] ; P < .001 ) , insulin ( mean difference , 49.6 μU/mL [ 95 % CI , 38.2 - 61.1 ] ; P < .001 ) , and glucagon-like polypeptide 1 ( mean difference , 2.1 pmol/L [ 95 % CI , 0.9 - 3.2 ] ; P = .01 ) . CONCLUSION AND RELEVANCE In a series of exploratory analyses , consumption of fructose compared with glucose result ed in a distinct pattern of regional CBF and a smaller increase in systemic glucose , insulin , and glucagon-like polypeptide 1 levels Factors controlling cerebral blood flow ( CBF ) during exercise are complex and incompletely known . Different techniques have shown partly contradictory results of changes in regional and global cerebral perfusion during dynamic exercise in healthy subjects . To eluci date the global CBF response to supine stepwise increasing physical exercise , we measured blood flow in the left common carotid artery ( QCCA ) and the left internal carotid artery ( QICA ) simultaneously with the blood flow velocity in the ipsilateral middle cerebral artery ( VMCA ) using duplex ultrasonography and transcranial Doppler ultrasonography . During moderate exercise intensity ( 60 - 67 % of maximal capacity ) , the VMCA increased 14 % ( P < 0.001 ) , the QICA 17 % ( P < 0.01 ) , and the QCCA 33 % ( P < 0.001 ) compared with baseline values . High physical exercise intensity ( 80 - 90 % of maximal capacity ) tended to reduce VMCA and QICA compared with moderate exercise , in contrast to a continued increase in QCCA . The results indicate an increased global CBF during exercise . This increase was reduced during hard exercise due to a decrease of the arterial PCO2 secondary to hyperventilation Background and Purpose — Pre clinical studies have revealed that the endogenous nitric oxide synthase inhibitor , asymmetric dimethylarginine ( ADMA ) , increases vascular tone in cerebral blood vessels . Marked elevations of ADMA blood levels were found in patients with diseases characterized by decreased cerebral perfusion , such as ischemic stroke . Arterial stiffness is an independent predictor of stroke and other adverse cardiovascular events . The aim of this study was to investigate the influence of a systemic subpressor dose of ADMA on arterial stiffness and cerebral perfusion in humans . Methods — Using a double-blind , vehicle-controlled study design , we allocated 20 healthy men in r and om order to infusion of either ADMA ( 0.10 mg ADMA/kg per min ) or vehicle over a period of 40 minutes . Arterial stiffness was assessed noninvasively by pulse wave analysis . All volunteers underwent measurement of cerebral perfusion by dynamic contrast-enhanced perfusion magnetic resonance imaging of the brain . Results — Infusion of ADMA significantly decreased total cerebral perfusion by 15.1±4.5 % ( P=0.007 ) , whereas blood flow in the vehicle group increased by 7.7±2.8 % ( P=0.02 ) . ADMA also increased arterial stiffness as assessed by measurement of the augmentation index ( −12.6±1.9 to −9.6±1.5 , P=0.007 ) . Conclusions — Our results document for the first time that subpressor doses of ADMA increase vascular stiffness and decrease cerebral perfusion in healthy subjects . Thus , ADMA is an important endogenous modulator of cerebral vascular tone and may be involved in the pathogenesis of cerebrovascular disease OBJECTIVES To investigate changes in resting cerebral blood flow ( CBF ) after acute sleep restriction . To investigate the extent to which changes in CBF after sleep restriction are related to drowsiness as manifested in eye-video . DESIGN Participants were scanned for 5 min using arterial spin labeling ( ASL ) perfusion imaging after both sleep-restricted and rested nights . Participants were rated for visual signs of drowsiness in the eye-video recorded during the scan . SETTING Lying supine in a 3-Tesla magnetic resonance imaging scanner . PARTICIPANTS Twenty healthy adults ( age 20 - 37 yr ) with no history of neurologic , psychiatric , or sleep disorder , and with usual time in bed of 7.0 - 8.5 h. INTERVENTIONS In the night before the sleep-restricted session , participants were restricted to 4 h time in bed . RESULTS There was an overall reduction in CBF in the right-lateralized fronto-parietal attentional network after acute sleep restriction , although this was largely driven by participants who showed strong signs of drowsiness in the eye-video after sleep restriction . Change in CBF correlated with change in drowsiness in the basal forebrain-cingulate regions . In particular , there was a pronounced increase in CBF in the basal forebrain and anterior and posterior cingulate cortex of participants who remained alert after sleep restriction . CONCLUSIONS The pattern of cerebral activity after acute sleep restriction is highly dependent on level of drowsiness . Nondrowsy individuals are able to increase activity in the arousal-promoting brain regions and maintain activity in attentional regions . In contrast , drowsy individuals are unable to maintain arousal and show decreased activity in both arousal-promoting and attentional regions OBJECTIVE Previous studies have demonstrated hemodynamic changes at different phases in the menstrual cycle , but the cerebral circulation has not been investigated . Our aim was to study carotid and cerebral blood flow during the menstrual cycle using Doppler ultrasound . Two different techniques of Doppler waveform analysis were used : st and ard Doppler indices and Laplace transform analysis ( LTA ) , which may provide additional hemodynamic information . DESIGN This was a prospect i ve study of healthy volunteers who were providing pre-conception data for a subsequent longitudinal study set in the Department of Obstetrics and Gynaecology , Nottingham University Hospital . Nineteen women were studied in the mid-follicular and mid-luteal phases of 27 ovulatory menstrual cycles . Doppler recordings were obtained from the internal and external carotid and middle cerebral arteries . The st and ard Doppler indices ( systolic/diastolic ratio , pulsatility index and resistance index ) and LTA parameters were calculated . RESULTS The st and ard Doppler indices were all significantly higher in the luteal compared to the follicular phase in the right middle cerebral artery ( p < 0.05 ) . However , no changes were seen in the st and ard indices in the carotid arteries or in any of the LTA parameters in any artery . Using the LTA , vessel wall stiffness was greater and absolute velocity of flow lower in the middle cerebral compared to the carotid arteries . CONCLUSIONS Increased ventilation and a subsequent lowering of alveolar CO2 pressure secondary to a raised progesterone level in the mid-luteal phase could account for the observed changes within the middle cerebral artery . Under the conditions of this study the LTA appears less sensitive at detecting alterations in downstream resistance compared to the st and ard Doppler indices UNLABELLED We tested the hypothesis that educational level influences regional cerebral blood flow ( rCBF ) in Alzheimer 's disease ( AD ) patients . METHODS The severity of AD was measured with the Cognitive Ability Screening Instrument ( age and education adjusted ) . rCBF was assessed using (99m)Tc-hexamethylpropyleneamine oxime brain SPECT ; differences in rCBF between groups with different educational levels were determined using statistical parametric mapping ( SPM ) . RESULTS In matched low-education ( < or = 6 y ; n = 29 ) and high-education ( > 6 y ; n = 29 ) groups , SPM revealed 2 statistically significant clusters of voxels with higher rCBF in the high-education group : one in the left lateral inferior , middle , and superior temporal gyrus ; another in the left medial temporal area to the left inferior frontal gyrus . CONCLUSION We provide biologic evidence that education may lead to relatively higher rCBF in specific areas in AD patients , which may explain the effects of education on clinical manifestations of AD Complex mental activity induces improvements in cognition , brain function , and structure in animals and young adults . It is not clear to what extent the aging brain is capable of such plasticity . This study exp and s previous evidence of generalized cognitive gains after mental training in healthy seniors . Using 3 MRI-based measurements , that is , arterial spin labeling MRI , functional connectivity , and diffusion tensor imaging , we examined brain changes across 3 time points pre , mid , and post training ( 12 weeks ) in a r and omized sample ( n = 37 ) who received cognitive training versus a control group . We found significant training-related brain state changes at rest ; specifically , 1 ) increases in global and regional cerebral blood flow ( CBF ) , particularly in the default mode network and the central executive network , 2 ) greater connectivity in these same networks , and 3 ) increased white matter integrity in the left uncinate demonstrated by an increase in fractional anisotropy . Improvements in cognition were identified along with significant CBF correlates of the cognitive gains . We propose that cognitive training enhances resting-state neural activity and connectivity , increasing the blood supply to these regions via neurovascular coupling . These convergent results provide preliminary evidence that neural plasticity can be harnessed to mitigate brain losses with cognitive training in seniors Middle cerebral artery mean velocity ( MCAvmean ) is attenuated with increasing age both at rest and during exercise . The aim of this study was to determine the influence of the age-dependent reduction in arterial Pco2 ( PaCO2 ) and physical fitness herein . We administered supplemental CO2 ( CO2 trial ) or no additional gas ( control trial ) to the inspired air in a blinded and r and omized manner , and assessed middle cerebral artery mean flow velocity during grade d exercise in 1 ) 21 young [ Y ; age 24 ± 3 yr ( ±SD ) ] volunteers of whom 11 were trained ( YT ) and 10 considered untrained ( YUT ) , and 2 ) 17 old ( O ; 66 ± 4 yr ) volunteers of whom 8 and 9 were considered trained ( OT ) and untrained ( OUT ) , respectively . A resting hypercapnic reactivity test was also performed . MCAvmean and PaCO2 were lower in O [ 44.9 ± 3.1 cm/s and 30 ± 1 mmHg ( ±SE ) ] compared with Y ( 59.3 ± 2.3 cm/s and 34 ± 1 mmHg , P < 0.01 ) at rest , independent of aerobic fitness level . The age-related decreases in MCAvmean and PaCO2 persisted during exercise . Supplemental CO2 reduced the age-associated decline in MCAvmean by 50 % , suggesting that PaCO2 is a major component in the decline . On the other h and , relative hypercapnic reactivity was neither influenced by age ( P = 0.46 ) nor aerobic fitness ( P = 0.36 ) . Although supplemental CO2 attenuated exercise-induced reduction in cerebral oxygenation ( near-infrared spectroscopy ) , this did not influence exercise performance . In conclusion , PaCO2 contributes to the age-associated decline in MCAvmean at rest and during exercise ; however exercise capacity did not diminish this age effect Mental stress causes a substantial sympathetic response , thus increasing myocardial blood flow ( MBF ) . However , the effects of mental stress on global CBF have not been eluci date d. In this study , changes in CBF and MBF in relation to mental stress were measured by a dual positron emission tomography system that can measure CBF and MBF simultaneously . CBF and MBF were measured in 10 healthy men with O-15 labeled water at rest ( baseline ) and during the performance of a mental task that required subtraction of 7s serially from a four-digit number . Baseline global CBF and values obtained during the mental activity were 0.42±0.05 and 0.45±0.06 ml/ml/min ( mean±SD ) , respectively . Baseline MBF and values obtained during mental activity were 0.61±0.12 and 1.09 ±0.58 ml/ml/min , respectively . Percent changes in CBF and MBF during mental stress were 6±11 % and 78±73 % , respectively . No significant difference was observed in PaCO2 level between the mental stress and baseline conditions . MBF , blood pressure , heart rate , and plasma concentrations of adrenaline and noradrenaline increased significantly during mental stress . Sympathetic stimulation is reported to cause cerebral vasoconstriction and reduce CBF in animals . Although such a sympathetic response was observed in relation to mental stress , no significant change in CBF was observed in our subjects BACKGROUND AND PURPOSE Recent evidence suggests that physiological changes in the concentration of endogenous estrogens may influence stroke outcome . The purpose of this study was to determine a menstrual cycle-related profile of blood flow through the carotid arteries and its correlation with estrogen concentration . METHODS The flow velocity and cross-sectional area of the common carotid artery , internal carotid artery ( ICA ) , and external carotid artery ( ECA ) were measured with duplex Doppler sonography throughout the menstrual cycle in 14 healthy women . Concentration of plasma 17beta-estradiol , progesterone , hematocrit , hemoglobin , and blood pressure were also determined . RESULTS In the follicular phase , the concentration of estrogen increased to reach a peak on day 14 , whereas concentration of progesterone remained low . The mean and end-diastolic velocities in the ICA increased on average by 15 % of their base values , along with increasing concentrations of estrogen ( r=0.59 and 0.65 , respectively ) . The profile of flow velocity changes in this artery corresponded to the profile of estrogen concentration . In contrast to the ICA , flow velocities in the ECA decreased from their base value , reaching their minimum in the luteal phase . The mean flow velocity in the common carotid artery increased on day 14 by just 2 % of its base value . The lumen of the carotid arteries was stable throughout the cycle . Hematocrit , hemoglobin , and systolic blood pressure also remained unchanged . CONCLUSIONS Increased concentration of endogenous estrogen correlates with substantial augmentation of flow in the internal carotid artery . This promotion of flow is caused mainly by decreased cerebrovascular resistance with consequent " stealing " of blood from the ECA This investigation compared patterns of regional cerebral blood flow ( rCBF ) during exercise recovery both with and without postexercise hypotension ( PEH ) . Eight subjects were studied on 3 days with r and omly assigned conditions : 1 ) after 30 min of rest ; 2 ) after 30 min of moderate exercise ( M-Ex ) at 60 - 70 % heart rate ( HR ) reserve during PEH ; and 3 ) after 30 min of light exercise ( L-Ex ) at 20 % HR reserve with no PEH . Data were collected for HR , mean blood pressure ( MBP ) , and ratings of perceived exertion and relaxation , and rCBF was assessed by use of single-photon-emission computed tomography . With the use of ANOVA across conditions , there were differences ( P < 0.05 ; mean + /- SD ) from rest during exercise recovery from M-Ex ( HR = + 12 + /- 3 beats/min ; MBP = -9 + /- 2 mmHg ) , but not from L-Ex ( HR = + 2 + /- 2 beats/min ; MBP = -2 + /- 2 mmHg ) . After M-Ex , there were decreases ( P < 0.05 ) for the anterior cingulate ( -6.7 + /- 2 % ) , right and left inferior thalamus ( -10 + /- 3 % ) , right inferior insula ( -13 + /- 3 % ) , and left inferior anterior insula (-8 + /- 3 % ) , not observed after L-Ex . There were rCBF decreases for leg sensorimotor regions after both M-Ex ( -15 + /- 4 % ) and L-Ex ( -12 + /- 3 % ) and for the left superior anterior insula ( -7 + /- 3 % and -6 + /- 3 % ) , respectively . Data show that there are rCBF reductions within specific regions of the insular cortex and anterior cingulate cortex coupled with a postexercise hypotensive response after M-Ex . Findings suggest that these cerebral cortical regions , previously implicated in cardiovascular regulation during exercise , may also be involved in PEH Cocaine-induced hypoperfusion , a risk factor for ischemic stroke , has not been fully characterized during experimental drug-taking among individuals with cocaine use disorder . We sought to examine cocaine 's dose-dependent , time-related effects on cerebral blood flow . In a double-blind , r and omized human laboratory study with a counterbalanced order of drug administration , 31 male and female subjects with cocaine use disorder were divided into two groups receiving either ( a ) low-dose cocaine ( 0.325 mg/kg intravenously ) or placebo ( N = 15 ) or ( b ) high-dose cocaine ( 0.650 mg/kg intravenously ) or placebo ( N = 16 ) . The different dose conditions were administered on test days separated by a rest period of ≥48 h. Cerebral blood flow was assessed quantitatively using H2O15 positron emission tomography . Experimentally administered low- and high-dose cocaine conditions versus their corresponding placebo conditions were associated with global and regional hypoperfusion . The trend for high- versus low-dose cocaine to be associated with greater hypoperfusion achieved statistical significance only for the dopamine-rich sublobar and midbrain regions . Cocaine 's hypoperfusion effects were maximal at 8 mins after infusion ( i.e. , at about the expected peak of intravenous cocaine levels ) and had mostly dissipated by 32 mins after infusion . Although hypoperfusion occurred throughout the brain , the left hemispheric dopamine-rich sublobar region was the most severely affected . Cocaine-induced cerebral hypoperfusion is associated with the time course of its pharmacological effects , and dopamine-rich areas , particularly in the left hemisphere , may be most vulnerable . Increasingly larger doses of cocaine may be associated with greater risk for ischemic stroke BACKGROUND The hypothalamus is the central homeostatic control region of the brain and , therefore , highly influenced by nutrients such as glucose and fat . Immediate and prolonged homeostatic effects of glucose ingestion have been well characterized . However , studies that used stimulation with fat have mainly investigated immediate perceptional processes . Besides homeostatic processes , the gustatory cortex , including parts of the insular cortex , is crucial for the processing of food items . OBJECTIVE The aim of this study was to investigate the effect of high- compared with low-fat meals on the hypothalamus and the insular cortex . DESIGN Eleven healthy men participated in a single-blinded , functional MRI study of high- and low-fat meals on 2 measurement days . Cerebral blood flow ( CBF ) was measured before and 30 and 120 min after intake of high- and low-fat yogurts . Hunger was rated and blood sample s were taken before each CBF measurement . RESULTS High-fat yogurt induced a pronounced decrease in CBF in the hypothalamus , and the corresponding CBF change correlated positively with the insulin change . Furthermore , insular activity increased after 120 min in the low-fat condition only . The CBF change in both regions correlated positively in the high-fat condition . CONCLUSIONS The decrease in hypothalamic activity and the interaction with the insular cortex elicited by fat may contribute to an efficient energy homeostasis . Therefore , fat might be a modulator of homeostatic and gustatory brain regions and their interaction . This trial was registered at clinical trials.gov as NCT01516021 A cross-sectional study of cerebral blood flow ( CBF ) levels in 268 neurologically normal volunteers contrasting nonsmokers , smokers who quit , and current cigarette smokers indicated that subjects who quit smoking had significantly higher cerebral perfusion levels than subjects who had continued to smoke but remained lower than subjects without a history of cigarette smoking . All subjects were matched for age and sex , and smoking groups were matched for duration and amount of smoking . A prospect i ve study of 11 subjects who were able to stop smoking in which CBF levels were available both antecedent to and following cessation of the habit indicated that significant gains occurred in cerebral perfusion levels within one year following cessation of smoking . A control group of 22 subjects who continued to smoke ( matched for age , sex , duration of smoking , and duration of time between baseline and follow-up ) showed no change in CBF values . A correlation between magnitude of CBF change and duration of cessation of cigarette smoking demonstrated a significant linear increase in CBF during the one-year period . These results suggest that elderly individuals who have smoked for three to four decades can benefit substantially by abstaining from cigarette smoking and that significant improvement in cerebral circulation occurs within a relatively short period Rationale Although the subjective effects of caffeine abstinence , acute and chronic administration , and tolerance are well described , the corresponding neurophysiological effects are not . Objectives Caffeine withdrawal , acute caffeine effects , caffeine tolerance , and net beneficial effects of chronic caffeine administration were investigated using cerebral blood flow velocity , quantitative electroencephalography ( EEG ) , and subjective effects . Material s and methods Sixteen regular caffeine users participated in this double-blind , within-subject study during which they received acute caffeine and placebo challenges ( 1 ) while maintained on 400 mg caffeine daily for ≥14 days and ( 2 ) while maintained on placebo for ≥14 days . Blood flow velocity was determined for the middle ( MCA ) and anterior ( ACA ) cerebral arteries using pulsed transcranial Doppler sonography . EEG was recorded from 16 scalp sites . Subjective effects were assessed with question naires . Results Acute caffeine abstinence ( evaluated 24 h after placebo substitution ) increased mean , systolic , and diastolic velocity in the MCA and ACA and decreased pulsatility index in the MCA . Acute caffeine abstinence increased EEG theta and decreased beta 2 power . Acute caffeine abstinence also increased measures of Tired , Fatigue , Sluggish , and Weary and decreased ratings of Energetic , Friendly , Lively , and Vigor . Acute caffeine effects were demonstrated across a wide range of measures , including cerebral blood flow , EEG , and subjective effects . Tolerance and “ complete ” tolerance were observed on subjective but not physiological measures . Chronic caffeine effects were demonstrated only on the measure of EEG beta 2 power . Conclusion Acute caffeine abstinence and administration produced changes in cerebral blood flow velocity , EEG , and subjective effects . Tolerance to subjective but not physiological measures was demonstrated . There was almost no evidence for net effects of chronic caffeine administration on these measures . Overall , these findings provide the most rigorous demonstration to date of physiological effects of caffeine withdrawal We investigated the effects on cerebral blood flow ( CBF ) of pure oxygen breathing exposure during dives in a group of professional divers , in both the normobaric ( NBO ) and the hyperbaric oxygen ( HBO ) breathing conditions . Using single photon emission computerized tomography ( SPECT ) and Tc-99 m hexamethylpropylenamine oxime ( HM-PAO ) , we studied 10 young divers and six normal volunteers . Divers were studied by SPECT in the NBO and HBO conditions , in two different sessions . The HBO state was obtained in a hyperbaric chamber at 2.8 ATA for 15 min . By ANOVA , we did not observe any significant difference in CBF distribution between controls and divers in both NBO and HBO conditions . By individual analysis , divers showed a decreased CBF in a total of 33 regions of interest ( ROIs ) during NBO and 46 ROIs during HBO with respect to control values . In particular , two divers showed a remarkable increase in the number of hypoperfused ROIs during HBO ( + 7 and + 5 ROIs , respectively ) . Pure oxygen breathing exposure in young divers is associated with a patchy distribution of brain areas of hypoperfusion . This phenomenon is more pronounced in the HBO state than in the NBO state . Further studies on CBF are needed to help identify divers potentially prone to harmful oxygen effects Followlng regular use , acute cessation of caffeine is associated with a characteristic withdrawal syndrome . Despite this , caffeine remains popular with its consumers . The aim of this study was to examine the physiologic and psychologic effects of small caffeine doses , administered in the form of a market-leading soft drink , on healthy women who were acutely withdrawn from caffeine . After 48-h abstinence and overnight fast , 11 healthy ( 22 to 40 years ) female volunteers , all regular caffeine users ( daily consumption 143 to 773 mg ) consumed using a double-blind . r and omized , controlled cross-over design either 2 tins of regular or caffeine-free Diet Coke . On both visits a Mars bar was eaten to prevent hypoglycaemia . Thus , the caffeine load was 76 or 10 mg respectively . Following ingestion of regular Diet Coke , there was a l0 % fall in middle cerebral artery velocity ( 95 % CI [ 6%-l4 % ] , p < 0.005 versus caffeine free ) and improvement in feelings of pleasure ( p < 0.046 ) and energy ( p < 0.037 ) . Intellectual function ( 4-choice reaction time ) was unaffected by caffeine status . On both visits , ingestion of Diet Coke induced a pressor response ( maximum rise in systolic pressure + 15+/- 2 mm Hg with caffeine and + l2 + /- 2 mm Hg with caffeine-free beverage , both p < 0.001 compared with baseline ) . In conclusion , in women acutely withdrawn from caffeine , ingestion of a popular soft beverage containing modest amounts of caffeine is associated with demonstrable physiologic and psychologic effects UNLABELLED Functional brain imaging is a powerful tool for examining the central nervous system ( CNS ) response to pharmacologic challenges . Amphetamine is of interest both because of its role as a stimulant of the dopaminergic system and because of its use to alter mood in mood-disordered patients , particularly in patients suffering from depression . In this study , we report the effects of oral D-amphetamine relative to placebo on regional cerebral blood flow ( rCBF ) measured by SPECT in healthy volunteers to characterize the normal CNS response to this primarily dopaminergic stimulant . METHODS SPECT was used to assess changes in rCBF induced by amphetamine in 16 healthy volunteers . Subjects received placebo and then 0.4 mg/kg oral amphetamine in a fixed-order single-blind design and were imaged on a triple-head tomograph . Another six healthy volunteers received placebo at both times to assess normal rCBF variability . rCBF changes were assessed with a three-dimensional voxel-based analysis integrated into an automated co registration system . Data were automatically normalized to whole-brain counts and coregistered . Result ant rCBF changes were evaluated parametrically through the formation of an image whose voxel values were based on the paired t statistic . RESULTS Amphetamine increased rCBF in two mesial prefrontal zones ( Brodmann 's areas 8 and 10 ) , inferior orbital frontal lobe ( area 11 ) , brain stem ( ventral tegmentum ) , anteromesial temporal lobe ( amygdala ) , and anterior thalamus . Amphetamine decreased rCBF to motor cortex , visual cortex , fusiform gyrus , posterolateral temporal lobe , and right lateral temporal lobe . CONCLUSION Our data suggest that amphetamine induces focal increases and decreases in rCBF in healthy volunteers in areas primarily innervated by dopamine pathways and in areas with secondary ( primarily limbic ) affiliations . These data are consistent with glucose metabolic data from autoradiographic studies in animals , in which the largest increases are seen in brain stem , followed by striatum , thalamus , and frontal and sensory cortices . Frontopolar and temporal increases observed in our study appear to be unique to humans Among neurologically normal volunteers approaching age 65 with an option for retirement , a four-year prospect i ve longitudinal study was design ed to examine effects of different levels of physical activity on cerebral perfusion by between-group comparisons . After the fourth year , cognitive performance was also tested . Three groups were compared , each composed of 30 elderly volunteers , assigned as follows : Group 1 , who continued to work ; Group 2 , who retired but participated in regular physical activities ; and Group 3 , who retired but did not participate in regular , planned physical activities . Retirees who elected to become physically inactive exhibited significant declines in cerebral blood flow ( CBF ) throughout four years of follow-up . Those who continued to work or retirees who elected to participate in regular activities sustained more constant CBF levels . Active retirees and those who continued to work also scored better on cognitive testing after the fourth year of follow-up compared to inactive retirees In order to verify the relationship between blood pressure and cerebral blood flow velocity in sub- clinical natural population , 1294 middle-aged and old Beijing rural residents were investigated in autumn 2002 . For all subjects , systolic blood flow velocities ( Vs ) in common carotid artery ( CCA ) , internal carotid artery ( ICA ) and middle cerebral artery ( MCA ) were detected with trans-cranial Doppler . Key factors such as anthropometry , medication use , blood pressure and blood biochemical analysis were investigated at the same time . After controlling for age , gender , diabetes , hypercholesterolaemia , smoking and body mass index , multivariate analysis showed that systolic blood pressure ( SBP ) correlated positively with Vs at MCA and slight negatively correlated with at CCA . As blood pressure rose by 10 mm Hg , the Vs at MCA increased by 1.63 cm/s . Duration of hypertension ( HD ) negatively correlated with Vs at MCA ( P<0.01 ) . The Vs at MCA in early-stage and chronic hypertensive patients were 92.9±1.9 and 84.1±2.3 cm/s , respectively . Antihypertensive treatment could modify the Vs at MCA towards a normal level by lowering blood pressure . In conclusion , the effect of hypertension on cerebral blood flow is complex . Vs at MCA positively correlated with SBP , but negatively related to HD . Antihypertensive treatment might be helpful to keep cerebral blood flow at a normal level We investigated the effect of moderate ( FiO2 13 % ) and light hypoxia ( FiO2 17 % ) and hypercapnia ( CO2 2 - 4 % ) with or without indomethacin on circulating levels of endothelin/endothelins ( ET ) and cerebral blood flow ( CBF ) in healthy volunteers . In protocol A , 23 subjects were exposed to moderate hypoxia . In protocol B , 29 subjects were r and omized to one of four groups : ( 1 ) placebo , ( 2 ) indomethacin , ( 3 ) indomethacin+light hypoxia and ( 4 ) indomethacin+hypercapnia . Indomethacin was given as an intravenous bolus dose of 0.4mgkg-1 body weight followed by continuous infusion of 0.4mgkg-1h-1 for 6h . Two different FiO2 were chosen , light hypoxia in protocol B was chosen due to application of a known cerebral vasoconstrictor with unknown effect on cerebral autoregulation . We found , that moderate hypoxia ( protocol A ) induced a significant increase in CBF from 59.0 to 73.0 ml 100 g-1 brain tissue min-1 ( p < 0.00005 ) with an increase in circulating levels of ET from 1.7 to 1.9fmol ml-1 plasma . However , this difference did not reach statistical significance ( p = 0.14 ) . We found , that indomethacin given intravenously ( protocol B groups 2 - 3 - 4 ) significantly elevated circulating levels of ET from 2.1 to 3.9fmol ml-1 plasma ( p < 0.00005 ) and decreased CBF from 60.5 to 39.5 ml 100g-1 brain tissue min-1 ( p < 0.00005 ) compared to baseline values . Exposure to light hypoxia/hypercapnia in the indomethacin group increased CBF to values not significantly different from baseline values . Although there was no statistical correlation between ET and CBF with and without indomethacin , our results suggest that ET may be involved in the cerebral vasoconstriction produced by indomethacin given intravenously OBJECTIVES The aim of this study was evaluation of the influence of hormonal replacement therapy ( HRT ) on the regional cerebral blood flow in postmenopausal women . METHODS The study group were 20 postmenopausal women , mean age 48.7 years ( S.D. + /- 4.9 years ) . The control group were ten regularly menstruating women , mean age 32.6 years ( S.D. + /- 13.2 years ) . In the studied group we measured the severity of climacteric syndrome with the use of Kupperman index and serum FSH and 17beta-estradiol level with the use of radioimmunological method . Cerebral blood flow was measured at rest using Single Photon Emission Computed Tomography ( SPECT ) . Tracer accumulation evaluation was performed in three slices defined as : cerebellar slice , thalamic slice and ventricular slice , the reference region was delineated in the cerebellum . In ten women with an impairment in the cerebral blood flow at the beginning of the study all the tests were repeated after 12 months of HRT . RESULTS Before HRT mean value of the Kupperman index in the study group was 29.8 points ( S.D. + /- 7.1 points ) ; 17beta-estradiol 27 pg/ml ( S.D. + /- 2 pg/ml ) ; FSH 56 IU/l ( S.D. + /- 49.5 IU/l ) ; SPECT study revealed cerebral blood flow impairment in ten women . In all the studied slices cerebral blood flow was lower in the study group than in the controls . After 12 months of HRT the mean value of the Kupperman index in the study group was 13.2 points ( S.D. + /- 2.1 points ) ( P < 0.05 ) ; 17beta-estradiol 44 pg/ml ( S.D. + /- 25 pg/ml ) ; FSH 36.4 IU/l ( S.D. + /- 57.3 ng/ml ) ; we found cerebral blood flow increase in all studied slices : right cerebellar slice : 5.2 % ; left cerebellar slice : 4.1 % ; right thalamic slice : 3.8 % ; left thalamic slice : 3.3 % ; right ventricular slice : 7.5 % * ; left ventricular slice : 6.7 % * ( * P < 0.05 ) . CONCLUSIONS Cerebral blood flow is lower in the postmenopausal women than in regularly menstruating women . HRT increases regional cerebral blood flow and this improvement coexists with an increase of serum 17beta-estradiol level The goal of this study was to investigate whether the supine resting perfusion of brain tissue in symptomatic patients suffering from orthostatic hypotension ( OH ) is changed compared to control subjects and whether an association exists between the resting perfusion and the severity of OH . Ten symptomatic OH patients and 8 control subjects were included in this study . One patient was retrospectively excluded because he suffered from multiple system atrophy . Systolic and diastolic blood pressure changes were measured during a tilting bed procedure . Cerebral blood flow , cerebral blood volume and mean transit time were determined by bolus-tracking perfusion MRI and correlated with blood pressure changes . Cerebral blood volume was significantly increased in OH patients compared with control subjects for white matter ( P = 0.019 ) and the mean transit time was significantly increased for gray ( P = 0.010 ) and white matter ( P = 0.015 ) . The cerebral blood flow of the gray ( r = 0.74 , P = 0.022 ) and white matter ( r = 0.75 , P = 0.020 ) was significantly , positively correlated with systolic blood pressure changes . The mean transit time in white matter was significantly , negatively correlated with systolic blood pressure changes ( r = -0.68 , P = 0.045 ) . This study suggests that in symptomatic patients with OH the cerebral perfusion of the brain in the resting , supine position correlates with the severity of OH as measured by postural changes in blood pressure The sale of energy drinks is often accompanied by a comprehensive and intense marketing with cl aims of benefits during periods of mental stress . As it has been shown that Red Bull negatively impacts human hemodynamics at rest , we investigated the cardiovascular and cerebrovascular consequences when Red Bull is combined with mental stress . In a r and omized cross-over study , 20 young healthy humans ingested either 355 ml of a can Red Bull or water and underwent 80 minutes after the respective drink a mental arithmetic test for 5 minutes . Continuous cardiovascular and cerebrovascular recordings were performed for 20 minutes before and up to 90 minutes after drink ingestion . Measurements included beat-to-beat blood pressure ( BP ) , heart rate , stroke volume , and cerebral blood flow velocity . Red Bull increased systolic BP ( + 7 mm Hg ) , diastolic BP ( + 4 mm Hg ) , and heart rate ( + 7 beats/min ) , whereas water drinking had no significant effects . Cerebral blood flow velocity decreased more in response to Red Bull than to water ( -9 vs -3 cm/s , p < 0.005 ) . Additional mental stress further increased both systolic BP and diastolic BP ( + 3 mm Hg , p < 0.05 ) and heart rate ( + 13 beats/min , p < 0.005 ) in response to Red Bull ; similar increases were also observed after water ingestion . In combination , Red Bull and mental stress increased systolic BP by about 10 mm Hg , diastolic BP by 7 mm Hg , and heart rate by 20 beats/min and decreased cerebral blood flow velocity by -7 cm/s . In conclusion , the combination of Red Bull and mental stress impose a cumulative cardiovascular load and reduces cerebral blood flow even under a mental challenge |
1,664 | 31,764,833 | PD-1/PD-L1 inhibitors appear to improve the antitumor activity in advanced gastric or gastroesophageal junction cancer patients .
However , single-agent PD-1/PD-L1 inhibitor did not result in a relative improvement in OS and PFS compared with chemotherapy in the treatment of patients with advanced gastric or gastroesophageal junction cancer . | BACKGROUND Current therapeutic options have limited efficacy for patients with advanced gastric or gastroesophageal junction cancer .
Immune checkpoint inhibition now has been increasingly used in advanced gastric or gastroesophageal junction cancer therapy .
To further underst and the efficacy and safety of anti-programmed cell death 1 ( PD-1 ) and its lig and 1 ( PD-L1 ) agents is critical for clinical practice .
We conducted this systematic review and meta- analysis to assess the benefit and risk of PD-1 and PD-L1 inhibitors . | BACKGROUND VEGFR-2 has a role in gastric cancer pathogenesis and progression . We assessed whether ramucirumab , a monoclonal antibody VEGFR-2 antagonist , in combination with paclitaxel would increase overall survival in patients previously treated for advanced gastric cancer compared with placebo plus paclitaxel . METHODS This r and omised , placebo-controlled , double-blind , phase 3 trial was done at 170 centres in 27 countries in North and South America , Europe , Asia , and Australia . Patients aged 18 years or older with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression on or within 4 months after first-line chemotherapy ( platinum plus fluoropyrimidine with or without an anthracycline ) were r and omly assigned with a central ised interactive voice or web-response system in a 1:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15 , plus paclitaxel 80 mg/m(2 ) intravenously on days 1 , 8 , and 15 of a 28-day cycle . A permuted block r and omisation , stratified by geographic region , time to progression on first-line therapy , and disease measurability , was used . The primary endpoint was overall survival . Efficacy analysis was by intention to treat , and safety analysis included all patients who received at least one treatment with study drug . This trial is registered with Clinical Trials.gov , number NCT01170663 , and has been completed ; patients who are still receiving treatment are in the extension phase . FINDINGS Between Dec 23 , 2010 , and Sept 23 , 2012 , 665 patients were r and omly assigned to treatment-330 to ramucirumab plus paclitaxel and 335 to placebo plus paclitaxel . Overall survival was significantly longer in the ramucirumab plus paclitaxel group than in the placebo plus paclitaxel group ( median 9·6 months [ 95 % CI 8·5 - 10·8 ] vs 7·4 months [ 95 % CI 6·3 - 8·4 ] , hazard ratio 0·807 [ 95 % CI 0·678 - 0·962 ] ; p=0·017 ) . Grade 3 or higher adverse events that occurred in more than 5 % of patients in the ramucirumab plus paclitaxel group versus placebo plus paclitaxel included neutropenia ( 133 [ 41 % ] of 327 vs 62 [ 19 % ] of 329 ) , leucopenia ( 57 [ 17 % ] vs 22 [ 7 % ] ) , hypertension ( 46 [ 14 % ] vs eight [ 2 % ] ) , fatigue ( 39 [ 12 % ] vs 18 [ 5 % ] ) , anaemia ( 30 [ 9 % ] vs 34 [ 10 % ] ) , and abdominal pain ( 20 [ 6 % ] vs 11 [ 3 % ] ) . The incidence of grade 3 or higher febrile neutropenia was low in both groups ( ten [ 3 % ] vs eight [ 2 % ] ) . INTERPRETATION The combination of ramucirumab with paclitaxel significantly increases overall survival compared with placebo plus paclitaxel , and could be regarded as a new st and ard second-line treatment for patients with advanced gastric cancer . FUNDING Eli Lilly and Company BACKGROUND Expression of PD-L1 has been shown to be upregulated in some patients with gastric cancer . As part of the phase 1b KEYNOTE-012 study , we aim ed to assess the safety and activity of the anti-PD-1 antibody pembrolizumab in patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction . METHODS This study was a multicentre , open-label , phase 1b trial done at 13 cancer research centres in the USA , Israel , Japan , South Korea , and Taiwan . We enrolled patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction . Patients received intravenous pembrolizumab at 10 mg/kg once every 2 weeks for 24 months or until progression or unacceptable toxic effects occurred . Response was assessed every 8 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1 . The primary objectives were safety in patients who received at least one dose of pembrolizumab and the proportion of patients achieving overall responses in patients who received at least one pembrolizumab dose and who either had a post-baseline scan or who discontinued therapy because of clinical disease progression or a treatment-related adverse event before the first post-baseline scan . The study is registered with Clinical Trials.gov , number NCT01848834 , and is ongoing but no longer enrolling patients . FINDINGS From Oct 23 , 2013 , to May 5 , 2014 , 39 patients were enrolled . 36 were evaluable for response by central assessment . Eight ( 22 % , 95 % CI 10 - 39 ) patients were judged to have had an overall response at central review ; all responses were partial . All 39 patients were included in the safety analyses . Five ( 13 % ) patients had a total of six grade 3 or 4 treatment-related adverse events , consisting of two cases of grade 3 fatigue , one case each of grade 3 pemphigoid , grade 3 hypothyroidism , and grade 3 peripheral sensory neuropathy , and one case of grade 4 pneumonitis . No treatment-related deaths occurred . INTERPRETATION In this population of patients with recurrent or metastatic PD-L1-positive gastric cancer , pembrolizumab had a manageable toxicity profile and promising antitumour activity , warranting further study in phase 2 and 3 trials . FUNDING Merck & BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche BACKGROUND Second-line chemotherapy for patients with oesophagogastric adenocarcinoma refractory to platinum and fluoropyrimidines has not shown benefits in health-related quality of life ( HRQoL ) . We assessed whether the addition of docetaxel to active symptom control alone can improve survival and HRQoL for patients . METHODS For this open-labelled , multicentre trial , we recruited patients aged 18 years or older from 30 UK centres . Patients were eligible if they had an advanced , histologically confirmed adenocarcinoma of the oesophagus , oesophagogastric junction , or stomach that had progressed on or within 6 months of treatment with a platinum-fluoropyrimidine combination . Patients could have an Eastern Cooperative Oncology Group performance status of 0 - 2 . We r and omly assigned patients using a central , computerised minimisation procedure to receive docetaxel plus active symptom control , or active symptom control alone ( 1:1 ; stratified by disease status , disease site , duration of response to previous chemotherapy , and performance status ) . Docetaxel was given at a dose of 75 mg/m(2 ) by intravenous infusion every 3 weeks for up to six cycles . The primary endpoint was overall survival , analysed by intention to treat . This is the report of the planned final analysis . This study is an International St and ardised R and omised Controlled Trial , number IS RCT N13366390 . FINDINGS Between April 21 , 2008 , and April 26 , 2012 , we recruited 168 patients , allocating 84 to each treatment group . After a median follow-up of 12 months [ IQR 10 - 21 ] ) and 161 ( 96 % ) deaths ( 80 in the docetaxel group , 81 in the active symptom control group ) , median overall survival in the docetaxel group was 5.2 months ( 95 % CI 4.1 - 5.9 ) versus 3.6 months ( 3.3 - 4.4 ) in the active symptom control group ( hazard ratio 0.67 , 95 % CI 0.49 - 0.92 ; p=0.01 ) . Docetaxel was associated with higher incidence of grade 3 - 4 neutropenia ( 12 [ 15 % ] patients vs no patients ) , infection ( 15 [ 19 % ] patients vs two [ 3 % ] patients ) , and febrile neutropenia ( six [ 7 % ] patients vs no patients ) . Patients receiving docetaxel reported less pain ( p=0.0008 ) and less nausea and vomiting ( p=0.02 ) and constipation ( p=0.02 ) . Global HRQoL was similar between the groups ( p=0.53 ) . Disease specific HRQoL measures also showed benefits for docetaxel in reducing dysphagia ( p=0.02 ) and abdominal pain ( p=0.01 ) . INTERPRETATION Our findings suggest that docetaxel can be recommended as an appropriate second-line treatment for patients with oesophagogastric adenocarcinoma that is refractory to treatment with platinum and fluoropyrimidine . FUNDING Cancer Research UK BACKGROUND The value of second-line therapy for metastatic gastric cancer is unclear . So far there are no r and omised phase III data comparing second-line chemotherapy to best supportive care ( BSC ) . In this prospect i ve , multicenter , open label , r and omised phase III study we compared irinotecan to BSC to evaluate the impact on survival of second-line chemotherapy . METHODS Eligible patients ( pts ) had metastatic or locally advanced gastro-oesophageal junction or gastric adenocarcinoma , objective tumour progression during or within 6months after first-line chemotherapy and ECOG performance status 0 - 2 . Stratification for time of progression after first-line therapy , ECOG PS and pretreatment secured even distribution of important prognostic factors . TREATMENT Arm A : Irinotecan 250mg/m(2)q3w ( first cycle ) to be increased to 350mg/m(2 ) , depending on toxicity . Arm B : BSC . FINDINGS Between 10/2002 and 12/2006 40 pts were r and omised . The study was closed prematurely due to poor accrual . Responsefor arm A ( 19 pts evaluable ) : No objective responses , SD 53 % , PD 47 % . Improvement of tumour related symptoms : Arm A 50 % of pts , arm B 7 % . Overall Survival : ( all events in 40 pts have occurred ) : The hazard ratio for death was reduced to 0.48 ( 95%CI 0.25 - 0.92 ) in the irinotecan-arm ( p=0.012 ) . Median survival arm A : 4.0months ( 95 % CI 3.6 - 7.5 ) , arm B : 2.4months ( 95 % CI 1.7 - 4.9 ) . INTERPRETATION Irinotecan as second-line chemotherapy significantly prolongs overall survival compared to BSC in the studied pts . Second-line chemotherapy can now be considered as a proven treatment option for metastatic or locally advanced gastric cancer . FUNDING The study was supported by a research grant from Aventis and Pfizer BACKGROUND Vascular endothelial growth factor ( VEGF ) and VEGF receptor-2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer . We aim ed to assess whether ramucirumab , a monoclonal antibody VEGFR-2 antagonist , prolonged survival in patients with advanced gastric cancer . METHODS We did an international , r and omised , double-blind , placebo-controlled , phase 3 trial between Oct 6 , 2009 , and Jan 26 , 2012 , at 119 centres in 29 countries in North America , Central and South America , Europe , Asia , Australia , and Africa . Patients aged 24 - 87 years with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression after first-line platinum-containing or fluoropyrimidine-containing chemotherapy were r and omly assigned ( 2:1 ) , via a central interactive voice-response system , to receive best supportive care plus either ramucirumab 8 mg/kg or placebo , intravenously once every 2 weeks . The study sponsor , participants , and investigators were masked to treatment assignment . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00917384 . FINDINGS 355 patients were assigned to receive ramucirumab ( n=238 ) or placebo ( n=117 ) . Median overall survival was 5·2 months ( IQR 2·3 - 9·9 ) in patients in the ramucirumab group and 3·8 months ( 1·7 - 7·1 ) in those in the placebo group ( hazard ratio [ HR ] 0·776 , 95 % CI 0·603 - 0·998 ; p=0·047 ) . The survival benefit with ramucirumab remained unchanged after multivariable adjustment for other prognostic factors ( multivariable HR 0·774 , 0·605 - 0·991 ; p=0·042 ) . Rates of hypertension were higher in the ramucirumab group than in the placebo group ( 38 [ 16 % ] vs nine [ 8 % ] ) , whereas rates of other adverse events were mostly similar between groups ( 223 [ 94 % ] vs 101 [ 88 % ] ) . Five ( 2 % ) deaths in the ramucirumab group and two ( 2 % ) in the placebo group were considered to be related to study drug . INTERPRETATION Ramucirumab is the first biological treatment given as a single drug that has survival benefits in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma progressing after first-line chemotherapy . Our findings vali date VEGFR-2 signalling as an important therapeutic target in advanced gastric cancer . FUNDING ImClone Systems BACKGROUND Patients with advanced gastric or gastro-oesophageal junction cancer refractory to , or intolerant of , two or more previous regimens of chemotherapy have a poor prognosis , and current guidelines do not recommend any specific treatments for these patients . We assessed the efficacy and safety of nivolumab , a fully human IgG4 monoclonal antibody inhibitor of programmed death-1 ( PD-1 ) , in patients with advanced gastric or gastro-oesophageal junction cancer who had been previously been treated with two or more chemotherapy regimens . METHODS In this r and omised , double-blind , placebo-controlled , phase 3 trial done at 49 clinical sites in Japan , South Korea , and Taiwan , eligible patients ( aged ≥20 years with unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer refractory to , or intolerant of , st and ard therapy [ including two or more previous chemotherapy regimens ] , with an Eastern Cooperative Oncology Group [ ECOG ] performance status of 0 - 1 , and naive to anti-PD-1 therapy or other therapeutic antibodies and pharmacotherapies for the regulation of T cells ) were recruited . Patients were r and omly assigned ( 2:1 ) using an interactive web response system to receive 3 mg/kg nivolumab or placebo intravenously every 2 weeks , stratified by country , ECOG performance status , and number of organs with metastases . Study treatment was continued until progressive disease per investigator assessment or onset of toxicities requiring permanent discontinuation . Patients and investigators were masked to group assignment . The primary endpoint was overall survival in the intention-to-treat population . Safety was analysed in all patients who received at least one dose of study treatment . This study is ongoing but not recruiting new patients , and is registered with Clinical Trials.gov , number NCT02267343 . FINDINGS Between Nov 4 , 2014 , and Feb 26 , 2016 , we r and omly assigned 493 patients to receive nivolumab ( n=330 ) or placebo ( n=163 ) . At the data cutoff ( Aug 13 , 2016 ) , median follow-up in surviving patients was 8·87 months ( IQR 6·57 - 12·37 ) in the nivolumab group and 8·59 months ( 5·65 - 11·37 ) in the placebo group . Median overall survival was 5·26 months ( 95 % CI 4·60 - 6·37 ) in the nivolumab group and 4·14 months ( 3·42 - 4·86 ) in the placebo group ( hazard ratio 0·63 , 95 % CI 0·51 - 0·78 ; p<0·0001 ) . 12-month overall survival rates were 26·2 % ( 95 % CI 20·7 - 32·0 ) with nivolumab and 10·9 % ( 6·2 - 17·0 ) with placebo . Grade 3 or 4 treatment-related adverse events occurred in 34 ( 10 % ) of 330 patients who received nivolumab and seven ( 4 % ) of 161 patients who received placebo ; treatment-related adverse events led to death in five ( 2 % ) of 330 patients in the nivolumab group and two ( 1 % ) of 161 patients in the placebo group . No new safety signals were observed . INTERPRETATION In this phase 3 study , the survival benefits indicate that nivolumab might be a new treatment option for heavily pretreated patients with advanced gastric or gastro-oesophageal junction cancer . Ongoing trials that include non-Asian patients are investigating nivolumab for advanced gastric or gastro-oesophageal junction cancer in various setting s and earlier treatment lines . FUNDING Ono Pharmaceutical and Bristol-Myers Squibb BACKGROUND Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes . We compared pembrolizumab with paclitaxel in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine . METHODS This r and omised , open-label , phase 3 study was done at 148 medical centres in 30 countries . Eligible patients were r and omised ( 1:1 ) in blocks of four per stratum with an interactive voice-response and integrated web-response system to receive either pembrolizumab 200 mg every 3 weeks for up to 2 years or st and ard-dose paclitaxel . Primary endpoints were overall survival and progression-free survival in patients with a programmed cell death lig and 1 ( PD-L1 ) combined positive score ( CPS ) of 1 or higher . Safety was assessed in all patients , irrespective of CPS . The significance threshold for overall survival was p=0·0135 ( one-sided ) . This trial is registered at Clinical Trials.gov , number NCT02370498 . FINDINGS Between June 4 , 2015 , and July 26 , 2016 , 592 patients were enrolled . Of the 395 patients who had a PD-L1 CPS of 1 or higher , 196 patients were assigned to receive pembrolizumab and 199 patients were assigned to receive paclitaxel . As of Oct 26 , 2017 , 326 patients in the population with CPS of 1 or higher had died ( 151 [ 77 % ] of 196 patients in the pembrolizumab group and 175 [ 88 % ] of 199 patients in the paclitaxel group ) . Median overall survival was 9·1 months ( 95 % CI 6·2 - 10·7 ) with pembrolizumab and 8·3 months ( 7·6 - 9·0 ) with paclitaxel ( hazard ratio [ HR ] 0·82 , 95 % CI 0·66 - 1·03 ; one-sided p=0·0421 ) . Median progression-free survival was 1·5 months ( 95 % CI 1·4 - 2·0 ) with pembrolizumab and 4·1 months ( 3·1 - 4·2 ) with paclitaxel ( HR 1·27 , 95 % CI 1·03 - 1·57 ) . In the total population , grade 3 - 5 treatment-related adverse events occurred in 42 ( 14 % ) of the 294 patients treated with pembrolizumab and 96 ( 35 % ) of the 276 patients treated with paclitaxel . INTERPRETATION Pembrolizumab did not significantly improve overall survival compared with paclitaxel as second-line therapy for advanced gastric or gastro-oesophageal junction cancer with PD-L1 CPS of 1 or higher . Pembrolizumab had a better safety profile than paclitaxel . Additional trials of pembrolizumab in gastric and gastro-oesophageal cancer are ongoing . FUNDING Merck Sharp & Dohme , a subsidiary of Merck & Abstract Background There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer ( GC/GEJC ) in whom two prior lines of therapy have failed . The r and omised , phase III JAVELIN Gastric 300 trial compared avelumab versus physician ’s choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC . Patients and methods Patients with unresectable , recurrent , locally advanced , or metastatic GC/GEJC were recruited at 147 sites globally . All patients were r and omised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician ’s choice of chemotherapy ( paclitaxel 80 mg/m2 on days 1 , 8 , and 15 or irinotecan 150 mg/m2 on days 1 and 15 , each of a 4-week treatment cycle ) ; patients ineligible for chemotherapy received best supportive care . The primary end point was overall survival ( OS ) . Secondary end points included progression-free survival ( PFS ) , objective response rate ( ORR ) , and safety . Results A total of 371 patients were r and omised . The trial did not meet its primary end point of improving OS { median , 4.6 versus 5.0 months ; hazard ratio (HR)=1.1 [ 95 % confidence interval ( CI ) 0.9–1.4 ] ; P = 0.81 } or the secondary end points of PFS [ median , 1.4 versus 2.7 months ; HR=1.73 ( 95 % CI 1.4–2.2 ) ; P > 0.99 ] or ORR ( 2.2 % versus 4.3 % ) in the avelumab versus chemotherapy arms , respectively . Treatment-related adverse events ( TRAEs ) of any grade occurred in 90 patients ( 48.9 % ) and 131 patients ( 74.0 % ) in the avelumab and chemotherapy arms , respectively . Grade ≥3 TRAEs occurred in 17 patients ( 9.2 % ) in the avelumab arm and in 56 patients ( 31.6 % ) in the chemotherapy arm . Conclusions Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy . Avelumab showed a more manageable safety profile than chemotherapy . Trial registration Clinical Trials.gov : NCT02625623 PURPOSE When design ing this trial , there was no evidence that salvage chemotherapy ( SLC ) in advanced gastric cancer ( AGC ) result ed in substantial prolongation of survival when compared with best supportive care ( BSC ) . However , SLC is often offered to pretreated patients with AGC for anecdotal reasons . PATIENTS AND METHODS Patients with AGC with one or two prior chemotherapy regimens involving both fluoropyrimidines and platinum and with an Eastern Cooperative Oncology Group performance status ( PS ) 0 or 1 were r and omly assigned in a ratio of 2:1 to SLC plus BSC or BSC alone . Choice of SLC-either docetaxel 60 mg/m(2 ) every 3 weeks or irinotecan 150 mg/m(2 ) every 2 weeks-was left to the discretion of investigators . Primary end point was overall survival ( OS ) . RESULTS Median OS was 5.3 months among 133 patients in the SLC arm and 3.8 months among 69 patients in the BSC arm ( hazard ratio , 0.657 ; 95 % CI , 0.485 to 0.891 ; one-sided P = .007 ) . OS benefit for SLC was consistent in most of the prospect ively defined subgroups , including age , PS , number of prior treatments , metastatic sites , hemoglobin levels , and response to prior chemotherapy . SLC was generally well tolerated , and adverse events were similar in the SLC and BSC arms . We found no median OS difference between docetaxel and irinotecan ( 5.2 v 6.5 months ; P = .116 ) . CONCLUSION To our knowledge , this is the largest phase III trial comparing SLC plus BSC with BSC alone in AGC . In pretreated patients , SLC is tolerated and significantly improves OS when added to BSC BACKGROUND Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction ( G/GEJ ) cancer in several countries after ATTRACTION-2 . To further improve the therapeutic efficacy of first-line therapy , exploration of a nivolumab-chemotherapy combination is warranted . In part 1 ( phase II ) of ATTRACTION-4 , the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin ( SOX ) or capecitabine plus oxaliplatin ( CapeOX ) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated . PATIENTS AND METHODS Patients were r and omized ( 1 : 1 ) to receive nivolumab ( 360 mg intravenously every 3 weeks ) plus SOX ( S-1 , 40 mg/m2 orally twice daily for 14 days followed by 7 days off ; oxaliplatin , 130 mg/m2 intravenously on day 1 every 3 weeks ) or CapeOX ( capecitabine , 1000 mg/m2 orally twice daily for 14 days followed by 7 days off ; oxaliplatin , 130 mg/m2 intravenously on day 1 every 3 weeks ) until disease progression , unacceptable toxicity , or consent withdrawal . RESULTS Of 40 r and omized patients , 39 ( nivolumab plus SOX , 21 ; nivolumab plus CapeOX , 18 ) and 38 ( 21 and 17 , respectively ) comprised the safety and efficacy population s , respectively . Most frequent ( > 10 % ) grade 3/4 treatment-related adverse events were neutropenia ( 14.3 % ) in the nivolumab plus SOX group , and neutropenia ( 16.7 % ) , anemia , peripheral sensory neuropathy , decreased appetite , type 1 diabetes mellitus , and nausea ( 11.1 % each ) in the nivolumab plus CapeOX group . No treatment-related death occurred . Objective response rate was 57.1 % ( 95 % confidence interval 34.0 - 78.2 ) with nivolumab plus SOX and 76.5 % ( 50.1 - 93.2 ) with nivolumab plus CapeOX . Median overall survival was not reached ( NR ) in both groups . Median progression-free survival was 9.7 months ( 5.8-NR ) and 10.6 months ( 5.6 - 12.5 ) , respectively . CONCLUSION Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer . ATTRACTION-4 has proceeded to part 2 ( phase III ) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX . CLINICAL TRIALS . GOV ID NCT02746796 |
1,665 | 25,208,549 | Results from exercise only interventions were inconclusive .
Evidence for nutrition only interventions was insufficient .
There was insufficient evidence for the effect of post-partum interventions on metabolic risk factors and inflammatory biomarkers . | Background Post-partum weight retention contributes to the risk of chronic obesity and metabolic alterations .
We conducted a systematic review of r and omized controlled trials ( RCTs ) on the effect of post-partum nutrition and exercise interventions on weight loss and metabolic outcomes . | BACKGROUND Recent prospect i ve data suggest that intake of rapidly digested and absorbed carbohydrates with a high dietary glycemic load is associated with an increased risk of ischemic heart disease . OBJECTIVE We examined whether a high dietary glycemic load was associated with elevated hs-CRP concentrations and whether this association was modified by body mass index ( BMI ; in kg/m(2 ) ) . DESIGN In 244 apparently healthy women , we measured plasma hs-CRP concentrations and determined average dietary glycemic loads with a vali date d semiquantitative food-frequency question naire . Using multiple regression models , we evaluated the association between dietary glycemic load and plasma hs-CRP after adjusting for age ; treatment status ; smoking status ; BMI ; physical activity level ; parental history of myocardial infa rct ion ; history of hypertension , diabetes , and high cholesterol ; postmenopausal hormone use ; alcohol intake ; and other dietary variables . RESULTS We found a strong and statistically significant positive association between dietary glycemic load and plasma hs-CRP . The median hs-CRP concentration for the lowest quintile of dietary glycemic load was 1.9 mg/L and for the highest quintile was 3.7 mg/L ; corresponding multivariate-adjusted geometric means were 1.4 and 3.8 mg/L , respectively ( P for trend < 0.01 ) . This association was significantly modified by BMI . Among women with a BMI greater-than-or-equal 25 , the multivariate-adjusted geometric mean hs-CRP concentration in the lowest quintile was 1.6 mg/L and in the highest quintile was 5.0 mg/L ; however , among women with a BMI < 25 , the corresponding means were 1.1 and 3.1 mg/L , respectively ( P = 0.01 for interaction ) . CONCLUSIONS Dietary glycemic load is significantly and positively associated with plasma hs-CRP in healthy middle-aged women , independent of conventional risk factors for ischemic heart disease . Exacerbation of the proinflammatory process may be a mechanism whereby a high intake of rapidly digested and absorbed carbohydrates increases the risk of ischemic heart disease , especially in overweight women prone to insulin resistance Background Pregnancy and childbirth are associated with weight gain in women , and retention of weight gained during pregnancy can lead to obesity in later life . Diet and physical activity are factors that can influence the loss of retained pregnancy weight after birth . Exercise guidelines exist for pregnancy , but recommendations for exercise after childbirth are virtually nonexistent . The aim of this study was to evaluate the effect of physical activity intervention based on pedometer on physical activity level and anthropometric measures of women after childbirth . Methods We conducted a r and omized controlled trial in which 66 women who had given birth 6 weeks to 6 months prior were r and omly assigned to receive either a 12 week tailored program encouraging increased walking using a pedometer ( intervention group , n = 32 ) or routine postpartum care ( control group , n = 34 ) . During the 12-week study period , each woman in the intervention group wore a pedometer and recorded her daily step count . The women were advised to increase their steps by 500 per week until they achieved the first target of 5000 steps per day and then continued to increase it to minimum of 10,000 steps per day by the end of 12th week . Assessed outcomes included anthropometric measures , physical activity level , and energy expenditure per week . Data were analyzed using the paired t-test , independent t-test , Mann-Whitney , chi-square , Wilcoxon , covariance analysis , and the general linear model repeated measures procedure as appropriate . Results After 12 weeks , women in the intervention group had significantly increased their physical activity and energy expenditure per week ( 4394 vs. 1651 calorie , p < 0.001 ) . Significant differences between-group in weight ( P = 0.001 ) , Body Mass Index ( P = 0.001 ) , waist circumference ( P = 0.001 ) , hip circumference ( P = 0.032 ) and waist-hip ratio ( P = 0.02 ) were presented after the intervention . The intervention group significantly increased their mean daily step count over the study period ( from 3249 before , to 9960 after the intervention , p < 0.001 ) . Conclusion A physical activity intervention based on pedometer is an effective means to increase physical activity ; reducing retention of weight gained during pregnancy and can improve anthropometric measures in postpartum women . Trial registration IS RCT N : I RCT OBJECTIVE : Since post-pregnancy weight retention may contribute to the development of obesity , we sought to determine whether a behavioral weight loss intervention was effective in returning women to their pre-pregnancy weight . METHOD : Ninety women who had given birth in the past 3–12 months and whose weight exceeded their pre-pregnancy weight by at least 6.8 kg were r and omly assigned to either : a ) a six-month behavioral weight loss intervention , delivered via correspondence or b ) a no-treatment control group . Assessment s of body weight , physical activity and eating patterns were conducted at pre-treatment and six months ( post-treatment ) . RESULTS : During the six month treatment , subjects in the correspondence condition lost significantly more weight than control subjects ( 7.8 kg vs 4.9 kg , P=0.03 ) and lost a greater percentage of their excess postpartum weight ( 79 % vs 44 % , P=0.01 ) . Furthermore , a significantly greater percentage of correspondence subjects than controls returned to their pre-pregnancy weight ( 33 % vs 11.5 % , P<0.05 ) . Weight loss in the correspondence group was correlated with completion of self-monitoring records ( r=0.50 , P<0.005 ) . CONCLUSIONS : A behavioral weight loss intervention , delivered via correspondence , appears to be effective in reducing women ’s postpartum weight retention . Future studies should examine the acceptability and the long-term impact of a correspondence postpartum weight loss intervention BACKGROUND & AIMS To establish whether probiotic supplemented dietary counselling influences maternal anthropometric measurements during and after pregnancy . METHODS At the first trimester of pregnancy 256 women were r and omly assigned to receive nutrition counselling to modify dietary intake according to current recommendations or as controls ; dietary intervention groups were further r and omized to receive probiotics Lactobacillus rhamnosus GG ( ATCC 53103 ) and Bifidobacterium lactis ( diet/probiotics ) or placebo ( diet/placebo ) capsules in a double-blind manner , whilst the controls received placebo ( control/placebo ) . The intervention lasted until the end of exclusive breastfeeding for up to six months . RESULTS The risk of central adiposity defined as waist circumference 80 cm or more was lowered in women in the diet/probiotics group compared with the control/placebo group ( OR 0.30 , 95%CI 0.11 - 0.85 , p = 0.023 adjusted for baseline BMI ) , whilst the diet/placebo group did not differ from the controls ( OR 1.00 , 95 % CI 0.38 - 2.68 , p = 0.994 ) at 6 months postpartum . The number needed to treat ( NNT ) with diet/probiotics to prevent one woman from developing a waist circumference of 80 cm or more was 4 . Healthy eating pattern at 12 months postpartum ( p = 0.001 ) and BMI prior to pregnancy ( p < 0.001 ) were strong determinants of BMI at 12 months postpartum when adjusted for dietary intervention and exercise . CONCLUSION The impact of probiotics-supplemented dietary counselling on central adiposity , may offer a novel means for the prevention and management of obesity . This trial was registered at clinical trials.gov as NCT 00167700 , section 3 Background / Objectives : Pregnancy is a life stage where excess weight gain may occur and the postpartum period is often characterised by weight retention . The aim of the current study was to evaluate the feasibility of undertaking a r and omised controlled trial of a weight loss intervention ( WeighWell ) in postpartum women living in areas of social disadvantage . Subjects/ Methods : The study aim ed to recruit 60 women who were not pregnant , 6–18 months postpartum with a body mass index > 25 kg/m2 living in areas of deprivation within Tayside , UK . Recruitment strategies focused on visits to community groups ; writing directly to postpartum women living in areas of deprivation and primary care teams who covered the most deprived 15 % of the population and advertising in community setting s. The 12-week intervention used motivational interviewing techniques to promote an energy deficit diet and increased physical activity , delivered by three face-to-face consultations plus three structured telephone calls . Results : Of 142 women screened , 63 were eligible and 52 ( 83 % ) were recruited and r and omised to an intervention ( n=29 ) or comparison group ( n=23 ) . Over the 12-week intervention , body weight changed significantly by −1.6±2.0 kg in the intervention group compared with + 0.2±2.2 kg in the comparison group , indicating the potential efficacy of the intervention . Loss to follow-up was 24 % in the intervention group and 39 % for the comparison group . Conclusions : The findings support the development of a definitive trial that embraces personalised recruitment strategies and the development of approaches to improve retention over a clinical ly relevant intervention period BACKGROUND The potential risks and benefits of regular exercise during lactation have not been adequately evaluated . We investigated whether regular aerobic exercise had any effects on the volume or composition of breast milk . METHODS Six to eight weeks post partum , 33 sedentary women whose infants were being exclusively breast-fed were r and omly assigned to an exercise group ( 18 women ) or a control group ( 15 women ) . The exercise program consisted of supervised aerobic exercise ( at a level of 60 to 70 percent of the heart-rate reserve ) for 45 minutes per day , 5 days per week , for 12 weeks . Energy expenditure , dietary intake , body composition , and the volume and composition of breast milk were assessed at 6 to 8 , 12 to 14 , and 18 to 20 weeks post partum . Maximal oxygen uptake and the plasma prolactin response to nursing were assessed at 6 to 8 and 18 to 20 weeks . RESULTS The women in the exercise group expended about 400 kcal per day during the exercise sessions but compensated for this energy expenditure with a higher energy intake than that recorded by the control women ( mean [ + /- SD ] , intake , 2497 + /- 436 vs. 2168 + /- 328 kcal per day at 18 to 20 weeks ; P < 0.05 ) . Maximal oxygen uptake increased by 25 percent in the exercising women but by only 5 percent in the control women ( P < 0.001 ) . There were no significant differences between the two groups in maternal body weight or fat loss , the volume or composition of the breast milk , the infant weight gain , or maternal prolactin levels during the 12-week study . CONCLUSIONS In this study , aerobic exercise performed four or five times per week beginning six to eight weeks post partum had no adverse effect on lactation and significantly improved the cardiovascular fitness of the mothers BACKGROUND The retention of weight gained during pregnancy may contribute to obesity . Lactation should promote weight loss , but weight loss is highly variable among lactating women . The risks associated with the restriction of energy intake during lactation have not been adequately evaluated . The purpose of this study was to determine whether weight loss by women during lactation affects the growth of their infants . METHODS We r and omly assigned 40 breast-feeding women who were overweight ( defined as a body-mass index [ the weight in kilograms divided by the square of the height in meters ] of 25 to 30 ) at 4 weeks post partum either to restrict their energy intake by 500 kcal per day and to exercise for 45 minutes per day for 4 days per week ( the diet- and -exercise group ) or to maintain their usual dietary intake and not exercise more than once per week for 10 weeks ( the control group ) . We measured the weight and fat mass of the women and the weight and length of the infants before , during , and at the end of the study period . RESULTS The mean ( + /-SD ) energy intake decreased by 544+/-471 kcal per day in the diet- and -exercise group . As compared with the control group , the women in the diet- and -exercise group lost more weight ( 4.8+/-1.7 kg vs. 0.8+/-2.3 kg , P<0.001 ) and fat mass ( 4.0+/-2.0 kg vs. 0.3+/-1.8 kg , P<0.001 ) . The gains in weight and length of the infants whose mothers were in the diet- and -exercise group ( 1925+/-500 g and 7.8+/-2.0 cm , respectively ) were not significantly different from those of the infants whose mothers were in the control group ( 1861+/-576 g and 7.3+/-1.7 cm ) . CONCLUSIONS Weight loss of approximately 0.5 kg per week between 4 and 14 weeks post partum in overweight women who are exclusively breast-feeding does not affect the growth of their infants OBJECTIVE To examine the longitudinal associations between a pregnancy and persistent changes in adiposity in young black and white women . DESIGN Prospect i ve cohort study with 5 years of follow-up . SETTING Participants recruited by community-based sampling ( Birmingham , Ala ; Chicago , Ill ; and Minneapolis , Minn ) and through the membership of a large prepaid health care plan ( Oakl and , Calif ) . PARTICIPANTS A total of 2788 women ( 53 % black ) aged 18 through 30 years were assessed at baseline ( 1985 through 1986 ) and reassessed at examination 2 ( 91 % retention ; 1987 through 1988 ) and examination 3 ( 86 % retention ; 1990 through 1991 ) . Women who remained nulliparous ( n = 925 ) during the 5-year follow-up were compared with women who had a single pregnancy of 28 weeks ' duration during that period and who were at least 12 months postpartum at follow-up ( primiparas , n = 89 ; multiparas , n = 114 ) . MAIN OUTCOME MEASURES Change in body weight and in waist-to-hip ratio during the 5-year period . Analyses were adjusted for demographic factors ( age and education ) , behavioral variables ( smoking and physical activity ) , and baseline level of adiposity . RESULTS Primiparas within both race groups gained 2 to 3 kg more weight during the 5-year period than did nulliparas in both adjusted and unadjusted analyses . Primiparas also had greater increases in waist-to-hip ratio that were independent of weight gain . Multiparas did not differ from nulliparas in adiposity change in either race group . At each level of parity , black women demonstrated greater adverse changes in adiposity than did white women . CONCLUSIONS These data suggest that women experience modest but adverse increases in body weight and fat distribution after a first pregnancy and that these changes are persistent BACKGROUND Current evidence suggests a combined treatment of postpartum weight loss of diet and exercise . However , to our knowledge , neither their separate and interactive effects nor long-term outcomes have been evaluated . OBJECTIVE We evaluated whether a 12-wk dietary behavior modification ( D ) treatment to decrease energy intake , physical exercise behavior modification ( E ) treatment to implement moderate aerobic exercise , or combined dietary and physical exercise behavior modification ( DE ) treatment compared with control ( usual care ) ( C ) reduces body weight in lactating women measured at the end of treatment and at a 1-y follow-up 9 mo after treatment termination . DESIGN At 10 - 14 wk postpartum , 68 lactating Swedish women with a prepregnancy BMI ( in kg/m² ) of 25 - 35 were r and omly assigned to D , E , DE , or C groups . Measurements were made at baseline , after the intervention , and again at a 1-y follow-up 9 mo later . A 2 × 2 factorial approach was used to analyze main and interaction effects of treatments . RESULTS Weight changes after the intervention and 1-y follow-up were -8.3 ± 4.2 and -10.2 ± 5.7 kg , respectively , in the D group ; -2.4 ± 3.2 and -2.7 ± 5.9 kg , respectively , in the E group ; -6.9 ± 3.0 and -7.3 ± 6.3 kg , respectively , in the DE group ; and -0.8 ± 3.0 and -0.9 ± 6.6 kg , respectively , in the C group . The main effects of D treatment , but not of E treatment , on weight were significant at both times ( P < 0.001 ) . CONCLUSIONS Dietary treatment provided clinical ly relevant weight loss in lactating postpartum women , which was sustained at 9 mo after treatment . The combined treatment did not yield significant weight or body-composition changes beyond those of dietary treatment alone BACKGROUND Postpregnancy weight retention contributes to the near-epidemic prevalence of obesity in the United States . This study examines the impact of an individualized , structured diet and physical activity intervention on weight loss in overweight women during the first year postpartum . METHODS Forty overweight postpartum women were r and omized to either a structured ( STR ) or a self-directed ( SELF ) intervention . Measurements included body weight , percent body fat , daily caloric intake , habitual physical activity , and cardiorespiratory fitness . Subjects in STR received individualized diet and physical activity prescriptions derived from baseline measurements . They met weekly for the first 12 weeks and kept daily food and activity diaries . Subjects in SELF received a single 1-hour educational session about diet and activity . RESULTS Only 23 of 40 participants remained in the study at 1 year postpartum . Of those , STR ( n = 13 ) had a significant weight loss ( 7.3 kg , p < 0.01 ) , a significant decrease in percent body fat ( 6 % , p < 0.01 ) , and no change in fat-free mass . SELF ( n = 10 ) had no significant change in weight , percent body fat , or fat-free mass . CONCLUSIONS Women who committed to this one class per week for 12 weeks postpartum had a high likelihood of successful weight loss that persisted at 1 year . Women who were overweight before pregnancy were unlikely to lose the pregnancy-related weight without the help of a formal intervention . This suggests that healthcare professionals should strongly encourage postpartum women to enroll in a structured diet and exercise program PURPOSE Women who are unable to return to a healthy weight by 6 months postpartum increase their risk factors for the development of chronic disease ( CD ; including metabolic syndrome , obesity , and cardiovascular disease ) . In a prospect i ve r and omized intervention study , we examined the effect of exercise intensity on risk factors for CD in the postpartum . We hypothesized that women receiving an intervention targeting healthy weight loss would have improved CD risk factors compared with women not receiving the intervention . Further , we hypothesized that nutrition control and moderate-intensity exercise would have the greatest improvement in CD risk factors versus low-intensity exercise . METHODS Women were r and omly assigned to a nutrition plus low-intensity ( 30 % HR reserve ; n = 20 ) or moderate-intensity ( 70 % HR reserve ; n = 20 ) exercise intervention group . The program consisted of supervised walking for 45 min , three to four times per week for 16 wk . All women were screened for CD at the beginning ( 7 - 8 wk postpartum ) and at the end ( 23 - 25 wk postpartum ) of the study . A historical control group of 20 sedentary postpartum women was matched by body mass index , age , and parity . RESULTS The low- and moderate-intensity groups lost more body mass ( -4.2 ± 4.0 and -5.0 ± 2.9 kg , respectively ) compared with the control group ( -0.1 ± 3.3 kg , P < 0.01 ) . Plasma low-density lipoprotein was reduced for the low- and moderate-intensity groups ( -0.29 ± 0.21 and -0.28 ± 0.17 mmol · L ) compared with the control group ( 0.03 ± 0.18 mmol · L , P = 0.015 ) . In addition , glucose concentrations were reduced and adiponectin concentrations increased ( P = 0.037 ) , regardless of exercise intensity , although the sedentary controls remained unchanged or at increased risk for CD . CONCLUSIONS Women receiving a postpartum intervention targeting healthy weight loss , regardless of exercise intensity , improved CD risk factors compared with women not receiving the intervention BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin The Internet offers a valuable re source for promotion of healthy eating and Web-based communication between the dietetics practitioner and client . In a 16-week intervention examining the effects of energy restriction ( 500 kcal/day ) and exercise on body composition in overweight/obese lactating women , MyPyramid Menu Planner for Moms was used to support dietary counseling . R and om assignment occurred at 4 weeks postpartum to either an Intervention group ( n=14 ) or Minimal Care group ( n=13 ) from 2008 through 2010 . Three 24-hour dietary recalls were obtained using the Nutrition Data System at 4 and 20 weeks postpartum . Individual MyPyramid Menu Planner accounts were created for the Intervention group and used in face-to-face dietary counseling . Repeated measures analysis of variance was used to test for differences between groups for change in dietary intake and weight . Changes in energy , saturated fat , and percent of energy from added sugars were significantly different between Intervention group and Minimal Care group ( -613 [ 521 ] kcal vs -171 [ 435 ] kcal ; P=0.03 ; -14.9 [ 14.0 ] g vs + 0.9 [ 13.4 ] g ; P<0.01 ; and -3.5 % [ 5.3 % ] vs + 2.2 % [ 4.8 % ] ; P<0.01 , respectively ) . The Intervention group significantly increased their whole fruit servings and decreased their total grain and milk servings compared with the Minimal Care group ( P<0.05 ) . The Intervention group lost significantly more weight ( -5.8 [ 3.5 ] kg ) than the Minimal Care group ( -1.6 [ 5.4 ] kg ) ( P=0.03 ) . Although participants must have access to an Internet-based computer and possess basic food knowledge , these results suggest MyPyramid Menu Planner might prove to be an effective dietary counseling support tool for improving dietary intake and promoting weight loss during lactation BACKGROUND Despite evidence that daily self-weighing is an effective strategy for weight control , concerns remain regarding the potential for negative psychological consequences . PURPOSE The goal of the study was to examine the impact of a daily self-weighing weight-loss intervention on relevant psychological constructs . DESIGN A 6-month RCT . SETTING / PARTICIPANTS The study sample ( N=91 ) included overweight men and women in the Chapel Hill NC area . INTERVENTION Between February and August 2011 , participants were r and omly assigned to a daily self-weighing intervention or delayed-intervention control group . The 6-month intervention included daily self-weighing for self-regulation of diet and exercise behaviors using an e-scale that transmitted weights to a study website . Weekly e-mailed lessons and tailored feedback on daily self-weighing adherence and weight-loss progress were provided . MAIN OUTCOME MEASURES Self-weighing frequency was measured throughout the study using e-scales . Weight was measured in-clinic at baseline , 3 months , and 6 months . Psychological outcomes were assessed via self-report at the same time points . RESULTS In 2012 , using linear mixed models and generalized estimating equation models , there were no significant differences between groups in depressive symptoms , anorectic cognitions , disinhibition , susceptibility to hunger , and binge eating . At 6 months , there was a significant group X time interaction for body dissatisfaction ( p=0.007 ) and dietary restraint ( p<0.001 ) , with the intervention group reporting lower body dissatisfaction and greater dietary restraint compared to controls . CONCLUSIONS Results indicate that a weight-loss intervention that focuses on daily self-weighing does not cause adverse psychological outcomes . This suggests that daily self-weighing is an effective and safe weight-control strategy among overweight adults attempting to lose weight . TRIAL REGISTRATION This study is registered at clinical trials.gov NCT01369004 CONTEXT Weight loss , sodium reduction , increased physical activity , and limited alcohol intake are established recommendations that reduce blood pressure ( BP ) . The Dietary Approaches to Stop Hypertension ( DASH ) diet also lowers BP . To date , no trial has evaluated the effects of simultaneously implementing these lifestyle recommendations . OBJECTIVE To determine the effect on BP of 2 multicomponent , behavioral interventions . DESIGN , SETTING , AND PARTICIPANTS R and omized trial with enrollment at 4 clinical centers ( January 2000-June 2001 ) among 810 adults ( mean [ SD ] age , 50 [ 8.9 ] years ; 62 % women ; 34 % African American ) with above-optimal BP , including stage 1 hypertension ( 120 - 159 mm Hg systolic and 80 - 95 mm Hg diastolic ) , and who were not taking antihypertensive medications . INTERVENTION Participants were r and omized to one of 3 intervention groups : ( 1 ) " established , " a behavioral intervention that implemented established recommendations ( n = 268 ) ; ( 2 ) " established plus DASH,"which also implemented the DASH diet ( n = 269 ) ; and ( 3 ) an " advice only " comparison group ( n = 273 ) . MAIN OUTCOME MEASURES Blood pressure measurement and hypertension status at 6 months . RESULTS Both behavioral interventions significantly reduced weight , improved fitness , and lowered sodium intake . The established plus DASH intervention also increased fruit , vegetable , and dairy intake . Across the groups , gradients in BP and hypertensive status were evident . After subtracting change in advice only , the mean net reduction in systolic BP was 3.7 mm Hg ( P<.001 ) in the established group and 4.3 mm Hg ( P<.001 ) in the established plus DASH group ; the systolic BP difference between the established and established plus DASH groups was 0.6 mm Hg ( P = .43 ) . Compared with the baseline hypertension prevalence of 38 % , the prevalence at 6 months was 26 % in the advice only group , 17 % in the established group ( P = .01 compared with the advice only group ) , and 12 % in the established plus DASH group ( P<.001 compared with the advice only group ; P = .12 compared with the established group ) . The prevalence of optimal BP ( < 120 mm Hg systolic and < 80 mm Hg diastolic ) was 19 % in the advice only group , 30 % in the established group ( P = .005 compared with the advice only group ) , and 35 % in the established plus DASH group ( P<.001 compared with the advice only group ; P = .24 compared with the established group ) . CONCLUSION Individuals with above-optimal BP , including stage 1 hypertension , can make multiple lifestyle changes that lower BP and reduce their cardiovascular disease risk Abstract Context / objective We describe the rationale , design , methods , and lessons learned conducting a treatment trial for major depressive disorder ( MDD ) or dysthymia in people with spinal cord injury ( SCI ) . Design A multi-site , double-blind , r and omized ( 1:1 ) placebo controlled trial of venlafaxine XR for MDD or dysthymia . Subjects were block r and omized and stratified by site , lifetime history of substance dependence , and prior history of MDD . Setting Six SCI centers throughout the United States . Participants Across participating centers , 2536 subjects were screened and 133 were enrolled into the trial . Subjects were 18–64 years old and at least 1 month post-SCI . Interventions Twelve-week trial of venlafaxine XR versus placebo using a flexible titration schedule . Outcome measures The primary outcome was improvement in depression severity at 12 weeks . The secondary outcome was improvement in pain . Results This article includes study methods , modifications prompted by a formative review process , preliminary data on the study sample and lessons learned . We describe common method ological and operational challenges conducting multi-site trials and how we addressed them . Challenges included study organization and decision making , staff training , obtaining human subjects approval , st and ardization of measurement and treatment , data and safety monitoring , subject screening and recruitment , unblinding and continuity of care , data base management , and data analysis . Conclusions The method ological and operational challenges we faced and the lessons we learned may provide useful information for research ers who aim to conduct clinical trials , especially in the area of medical treatment of depression in people with SCI |
1,666 | 26,620,449 | Effect size is not associated with impact factor , reporting of funding source , or reporting of conflicts of interest .
Conclusions The absence of associations between effect size and impact factor , reporting sources of funding , and conflicts of interest reflects positively on research and publisher conduct in the field .
Strong evidence of a large association between absolute magnitude of effect size and explicit reporting of ‘ no funding ’ suggests authors of unfunded trials are likely to report larger effect sizes , notwithst and ing direction .
This could relate in part to quality , re sources , and /or how pragmatic a trial is | Background Low back pain is a common and costly health complaint for which there are several moderately effective treatments .
In some fields there is evidence that funder and financial conflicts are associated with trial outcomes .
It is not clear whether effect sizes in back pain trials relate to journal impact factor , reporting conflicts of interest , or reporting funding . | OBJECTIVES To compare outcomes in perception of pain and disability for a group of patients suffering with chronic low-back pain ( CLBP ) when managed in a hospital by either a regional pain clinic or a chiropractor . DESIGN The study was a pragmatic , r and omized , controlled trial . SETTING The trial was performed at a National Health Service ( NHS ) hospital outpatient clinic ( pain clinic ) in the United Kingdom . SUBJECTS AND INTERVENTIONS Patients with CLBP ( i.e. , symptom duration of > 12 weeks ) referred to a regional pain clinic ( outpatient hospital clinic ) were assessed and r and omized to either chiropractic or pain-clinic management for a period of 8 weeks . The study was pragmatic , allowing for normal treatment protocol s to be used . Treatment was administered in an NHS hospital setting . OUTCOME MEASURES The Rol and -Morris Disability Question naire ( RMDQ ) and Numerical Rating Scale were used to assess changes in perceived disability and pain . Mean values at weeks 0 , 2 , 4 , 6 , and 8 were calculated . The mean differences between week 0 and week 8 were compared across the two treatment groups using Student 's t-tests . Ninety-five percent ( 95 % ) confidence intervals ( CIs ) for the differences between groups were calculated . RESULTS R and omization placed 12 patients in the pain clinic and 18 in the chiropractic group , of which 11 and 16 , respectively , completed the trial . At 8 weeks , the mean improvement in RMDQ was 5.5 points greater for the chiropractic group ( decrease in disability by 5.9 ) than for the pain-clinic group ( 0.36 ) ( 95 % CI 2.0 points to 9.0 points ; p = 0.004 ) . Reduction in mean pain intensity at week 8 was 1.8 points greater for the chiropractic group than for the pain-clinic group ( p = 0.023 ) . CONCLUSIONS This study suggests that chiropractic management administered in an NHS setting may be effective for reducing levels of disability and perceived pain during the period of treatment for a sub population of patients with CLBP OBJECTIVE For long-term treatment effects , patients with subacute back pain need to adhere to treatment recommendations beyond the prescribed exercise treatment . Adherence rates are as low as 30 % , so we developed a cognitive-behavioural training programme to enhance patients ' self-efficacy , maximise severity perceptions and reduce barrier perceptions . METHOD A 2 x 4 ( group x time ) repeated measurement design was applied . Forty-seven patients with non-specific , subacute back pain were r and omly assigned to a training group ( exercise treatment plus cognitive-behavioural training programme ) or a control group ( exercise treatment only ) . RESULTS Repeated measures ANOVA revealed significant main and interaction effects ; the training group reported enhanced self-efficacy and severity perceptions , reduced barrier perceptions , and self-reported that they exercised more often than the control group over time . However , no group differences regarding pain intensity emerged . CONCLUSION Our findings demonstrate that a short and inexpensive cognitive-behavioural training programme is an effective tool to enable back pain patients to follow treatment recommendations on a regular basis . PRACTICE IMPLICATION S The short and simple intervention can easily be conducted by personnel , other than psychologists , i.e. , physiotherapists OBJECTIVE To test the hypothesis that articles with negative results are more likely than articles with positive results to be published in journals with lower impact factor . DESIGN AND SETTING We selected all of the r and omized , placebo-controlled trials conducted during the neonatal period between October 1 , 1998 , and October 1 , 2003 . Trials were classified as having positive results or negative results ( significant or no significant difference , respectively ) . Only studies dealing with primary outcomes ( efficacy ) were included . MAIN OUTCOME MEASURES The impact factor of each journal was determined , and the sample size for each study was noted . RESULTS There were 233 articles that fulfilled the inclusion criteria . There was a significant difference between the 2 groups in terms of impact factor ( P = .03 ) but not sample size ( P = .30 ) . Impact factor correlated with both sample size and the type of study results ( positive results vs negative results ; P<.05 ) . CONCLUSION Articles with negative results are more likely than articles with positive results to be published in journals with lower impact factor STUDY DESIGN A controlled clinical trial . OBJECTIVES To assess the effects of an integrated back stability ( IBS ) programme on a chronic low back pain ( CLBP ) population in a time restricted private clinic environment . BACKGROUND Studies assessing stability training CLBP have reported inconsistent results . Methods used within trials vary , with some authors focusing on muscle isolation and others using whole body movements . IBS uses an exercise progression beginning with posturally based exercise and progressing from muscle isolation through to complex movements . METHODS AND MEASURES Fifty-nine chronic low back patients were divided into control ( n=32 ) and intervention ( n=27 ) groups . Participants in the intervention group were prescribed a 6 week individualized exercise programme in three stages . In stage 1 , exercises addressed posture and movement dysfunction and activated the core stabilizing muscles . In stage 2 , ' back fitness ' was enhanced using progressive exercise principles . Stage 3 emphasized technique specific actions . Participants in the control group received a backcare advice leaflet only . RESULTS Pre- and post-test scores were analysed for each of the outcome measures within the control group using a Wilcoxin signed ranks test . At an alpha level of p < or=0.0071 , no differences were observed . For the intervention group , a Mann-Whitney U-test showed significant differences between groups in the Rol and and Morris Disability Question aire ( RMDQ ) , short form McGill Pain Question naire ( SF-MPQ ) , and the Tampa Scale of Kinesiophobia ( TSK ) ( p < or=0.0071 ) . Patient satisfaction was assessed by question naire , 89 % of patients considering their level of pain and functional impairment acceptable following the programme . CONCLUSION IBS significantly reduced pain and disability in the subject group studied . Patients reported a positive experience of the programme OBJECTIVE To evaluate the effectiveness of the addition of back school to exercise and physical treatment modalities in relieving pain and improving the functional status of patients with chronic low back pain . DESIGN A r and omized controlled trial . PATIENTS A total of 146 patients with chronic low back pain were enrolled in the study . METHODS Subjects were divided into 2 groups : the back school group received exercise , physical treatment modalities and a back school programme ; and the control group received exercise and physical treatment modalities . Treatment efficacy was evaluated at the end of treatment and 3 months post-treatment , in terms of pain , measured with the Visual Analogue Scale , and functional status , measured with the Oswestry Low Back Pain Disability Question naire . RESULTS In both groups , Visual Analogue Scale and Oswestry Low Back Pain Disability Question naire were significantly reduced after therapy ( p < 0.01 ) , but the difference between the scores at the end of treatment and 3 months post-treatment was not significant . There was a significant improvement in Visual Analogue Scale and Oswestry Low Back Pain Disability Question naire in the back school group compared with the control group at the end of therapy and 3 months post-treatment ( p < 0.05 ) . CONCLUSION The addition of back school was more effective than exercise and physical treatment modalities alone in the treatment of patients with chronic low back pain INTRODUCTION Chronic , nonspecific low back pain is a difficult ailment to treat and poses an economic burden in terms of medical expenses and productivity loss . The aim of this study was to determine the efficacy and safety of intramuscular metylcobalamin in the treatment of chronic nonspecific low back pain . METHODS This was a double-blinded , r and omised , controlled experimental study . 60 patients were assigned to either the methylcobalamin group or the placebo group . The former received intramuscular injections of 500 mcg parenteral methylcobalamin in 1 ml solution three times a week for two weeks , and the placebo group received 1 ml normal saline . Patients were assessed with Oswestry Disability Index question naire Version 2.0 and Visual Analogue Scale pain score . They were scored before commencement of the injections and at two months interval . RESULTS Of the 60 patients , 27 received the placebo injections and 33 were given methylcobalamin injections . A total of 58 patients were available for review at two months ( placebo : n is 26 ; methylcobalamin : n is 32 ) . There was a significant improvement in the Oswestry Disability Index and Visual Analogue Scale pain scores in the methylcobalamin group as compared with the placebo group ( p-value less than 0.05 ) . Only minor adverse reactions such as pain and haematoma at the injection sites were reported by some patients . CONCLUSION Intramuscular methylcobalamin is both an effective and safe method of treatment for patients with nonspecific low back pain , both singly or in combination with other forms of treatment There is limited evidence that preprogrammed feedforward adjustments , which are modified in people with neurological and musculoskeletal conditions , can be trained and whether this depends on the type of training . As previous findings demonstrate consistent delays in feedforward activation of the deep abdominal muscle , transversus abdominis ( TrA ) , in people with recurrent low back pain ( LBP ) , we investigated whether training involving voluntary muscle activation can change feedforward mechanisms , and whether this depends on the manner in which the muscle is trained . Twenty-two volunteers with recurrent LBP were r and omly assigned to undertake either training of isolated voluntary activation of TrA or sit-up training to activate TrA in a non-isolated manner to identical amplitude . Subjects performed a trunk perturbation task involving arm movement prior to and after training , and surface and fine-wire electromyography ( EMG ) recordings were made from trunk and arm muscles . Following a single session of training of isolated voluntary activation of TrA , onset of TrA EMG was earlier during rapid arm flexion and extension , to more closely resemble the responses in pain-free individuals . The magnitude of change in TrA EMG onset was correlated with the quality of isolated training . In contrast , all of the abdominal muscles were recruited earlier during arm flexion after sit-up training , while onset of TrA EMG was further delayed during arm extension . The results provide evidence that training of isolated muscle activation leads to changes in feedforward postural strategies , and the magnitude of the effect is dependent on the type and quality of motor training BACKGROUND To our knowledge , verum acupuncture has never been directly compared with sham acupuncture and guideline -based conventional therapy in patients with chronic low back pain . METHODS A patient- and observer-blinded r and omized controlled trial conducted in Germany involving 340 outpatient practice s , including 1162 patients aged 18 to 86 years ( mean + /- SD age , 50 + /- 15 years ) with a history of chronic low back pain for a mean of 8 years . Patients underwent ten 30-minute sessions , generally 2 sessions per week , of verum acupuncture ( n = 387 ) according to principles of traditional Chinese medicine ; sham acupuncture ( n = 387 ) consisting of superficial needling at nonacupuncture points ; or conventional therapy , a combination of drugs , physical therapy , and exercise ( n = 388 ) . Five additional sessions were offered to patients who had a partial response to treatment ( 10%-50 % reduction in pain intensity ) . Primary outcome was response after 6 months , defined as 33 % improvement or better on 3 pain-related items on the Von Korff Chronic Pain Grade Scale question naire or 12 % improvement or better on the back-specific Hanover Functional Ability Question naire . Patients who were unblinded or had recourse to other than permitted concomitant therapies during follow-up were classified as nonresponders regardless of symptom improvement . RESULTS At 6 months , response rate was 47.6 % in the verum acupuncture group , 44.2 % in the sham acupuncture group , and 27.4 % in the conventional therapy group . Differences among groups were as follows : verum vs sham , 3.4 % ( 95 % confidence interval , -3.7 % to 10.3 % ; P = .39 ) ; verum vs conventional therapy , 20.2 % ( 95 % confidence interval , 13.4 % to 26.7 % ; P < .001 ) ; and sham vs conventional therapy , 16.8 % ( 95 % confidence interval , 10.1 % to 23.4 % ; P < .001 . CONCLUSIONS Low back pain improved after acupuncture treatment for at least 6 months . Effectiveness of acupuncture , either verum or sham , was almost twice that of conventional therapy Background The evidence that exercise intervention is effective for treatment of chronic low back pain comes from trials that are not placebo-controlled . Objective The purpose of this study was to investigate the efficacy of motor control exercise for people with chronic low back pain . Design This was a r and omized , placebo-controlled trial . Setting The study was conducted in an outpatient physical therapy department in Australia . Patients The participants were 154 patients with chronic low back pain of more than 12 weeks ’ duration . Intervention Twelve sessions of motor control exercise ( ie , exercises design ed to improve function of specific muscles of the low back region and the control of posture and movement ) or placebo ( ie , detuned ultrasound therapy and detuned short-wave therapy ) were conducted over 8 weeks . Measurements Primary outcomes were pain intensity , activity ( measured by the Patient-Specific Functional Scale ) , and patient 's global impression of recovery measured at 2 months . Secondary outcomes were pain ; activity ( measured by the Patient-Specific Functional Scale ) ; patient 's global impression of recovery measured at 6 and 12 months ; activity limitation ( measured by the Rol and -Morris Disability Question naire ) at 2 , 6 , and 12 months ; and risk of persistent or recurrent pain at 12 months . Results The exercise intervention improved activity and patient 's global impression of recovery but did not clearly reduce pain at 2 months . The mean effect of exercise on activity ( measured by the Patient-Specific Functional Scale ) was 1.1 points ( 95 % confidence interval [CI]=0.3 to 1.8 ) , the mean effect on global impression of recovery was 1.5 points ( 95 % CI=0.4 to 2.5 ) , and the mean effect on pain was 0.9 points ( 95 % CI=−0.01 to 1.8 ) , all measured on 11-point scales . Secondary outcomes also favored motor control exercise . Limitation Clinicians could not be blinded to the intervention they provided . Conclusions Motor control exercise produced short-term improvements in global impression of recovery and activity , but not pain , for people with chronic low back pain . Most of the effects observed in the short term were maintained at the 6- and 12-month follow-ups Tizanidine and aceclofenac individually have shown efficacy in the treatment of low back pain . The efficacy and tolerability of the combination have not yet been established . The objective of the study was to evaluate the efficacy and safety of aceclofenac-tizanidine fixed dose combination against aceclofenac alone in patients with acute low back pain . This double-blind , double-dummy , r and omized , comparative , multicentric , parallel group study enrolled 197 patients of either sex in the age range of 18–70 years with acute low back pain . The patients were r and omized to receive either aceclofenac ( 100 mg)–tizanidine ( 2 mg ) b.i.d or aceclofenac ( 100 mg ) alone b.i.d for 7 days . The primary efficacy outcomes were pain intensity ( on movement , at rest and at night ; on VAS scale ) and pain relief ( on a 5-point verbal rating scale ) . The secondary efficacy outcomes measures included functional impairment ( modified Schober ’s test and lateral body bending test ) and patient ’s and investigator ’s global efficacy assessment . aceclofenac – tizanidine was significantly superior to aceclofenac for pain intensity ( on movement , at rest and at night ; P < 0.05 ) and pain relief ( P = 0.00 ) on days 3 and 7 . There was significant increase in spinal flexion in both the groups from baseline on days 3 and 7 with significant difference in favour of the combination group ( P < 0.05 ) . There were significantly more number of patients with excellent to good response for the aceclofenac – tizanidine treatment as compared to aceclofenac alone ( P = 0.00 ) . Both the treatments were well tolerated . In this study , aceclofenac – tizanidine combination was more effective than aceclofenac alone and had a favourable safety profile in the treatment of acute low back pain This large , open-label , r and omized , parallel-group , multicenter study compared two oral sustained-release opioids (SROs)--AVINZA ( A-MQD ) , morphine sulfate extended-release capsules given once a day , and OxyContin ( O-ER ) , oxycodone modified-release tablets given twice a day -- in SRO-naive subjects ages 30 to 70 with chronic , moderate to severe low back pain . Of the 392 subjects enrolled and r and omized , 266 ( 132 in the A-MQD group and 134 in the O-ER group ) completed the opioid dose titration phase and entered an eight-week evaluation phase . During the evaluation phase , A-MQD achieved significantly better pain control than O-ER , as demonstrated by a greater decrease from baseline in pain scores obtained four times daily during weeks one , four , and eight ( p = 0.002 ) . The number of breakthrough-pain rescue medication doses adjusted for the number of patient days was significantly lower in the A-MQD group ( p < 0.0001 ) . Better pain control with A-MQD was achieved with a significantly lower daily opioid dose than with O-ER ( mean 69.9 mg and 91 mg morphine equivalents , respectively ; p = 0.0125 ) . Quality of sleep was significantly better with A-MQD for the entire evaluation phase ( p = 0.0026 ) . The incidence and severity of elicited opioid side effects were similar in the two groups . This trial demonstrated that once-daily A-MQD provides consistent around-the-clock pain relief in patients with low back pain . In patients who completed opioid dose titration , A-MQD was significantly better than O-ER for reducing pain and improving sleep , while requiring a lower daily opioid dose The objective of this study was to report on secondary analyses of a merged trial data set aim ed at exploring the potential importance of patient factors associated with clinical ly relevant improvements in non-acute , non-specific low back pain ( LBP ) . From 273 predominantly male army workers ( mean age 39 ± 10.5 years , range 20–56 years , 4 women ) with LBP who were recruited in three r and omized clinical trials , baseline individual patient factors , pain-related factors , work-related psychosocial factors , and psychological factors were evaluated as potential prognostic variables in a short-term ( post-treatment ) and a long-term logistic regression model ( 6 months after treatment ) . We found one dominant prognostic factor for improvement directly after treatment as well as 6 months later : baseline functional disability , expressed in Rol and –Morris Disability Question naire scores . Baseline fear of movement , expressed in Tampa Scale for Kinesiophobia scores , had also significant prognostic value for long-term improvement . Less strongly associated with the outcome , but also included in our final models , were supervisor social support and duration of complaints ( short-term model ) , and co-worker social support and pain radiation ( long-term model ) . Information about initial levels of functional disability and fear-avoidance behaviour can be of value in the treatment of patient population s with characteristics comparable to the current army study population ( e.g. , predominantly male , physically active , working , moderate but chronic back problems ) . Individuals at risk for poor long-term LBP recovery , i.e. , individuals with high initial level of disability and prominent fear-avoidance behaviour , can be distinguished that may need additional cognitive-behavioural treatment Background Effective strategies for the primary prevention of low back pain ( LBP ) remain elusive with few large-scale clinical trials investigating exercise and education approaches . The purpose of this trial was to determine whether core stabilization alone or in combination with psychosocial education prevented incidence of low back pain in comparison to traditional lumbar exercise . Methods The Prevention of Low Back Pain in the Military study was a cluster r and omized clinical study with four intervention arms and a two-year follow-up . Participants were recruited from a military training setting from 2007 to 2008 . Soldiers in 20 consecutive companies were considered for eligibility ( n = 7,616 ) . Of those , 1,741 were ineligible and 1,550 were eligible but refused participation . For the 4,325 Soldiers enrolled with no previous history of LBP average age was 22.0 years ( SD = 4.2 ) and there were 3,082 males ( 71.3 % ) . Companies were r and omly assigned to receive traditional lumbar exercise , traditional lumbar exercise with psychosocial education , core stabilization exercise , or core stabilization with psychosocial education , The psychosocial education session occurred during one session and the exercise programs were done daily for 5 minutes over 12 weeks . The primary outcome for this trial was incidence of low back pain result ing in the seeking of health care . Results There were no adverse events reported . Evaluable patient analysis ( 4,147/4,325 provided data ) indicated no differences in low back incidence result ing in the seeking of health care between those receiving the traditional exercise and core stabilization exercise programs . However , brief psychosocial education prevented low back pain episodes regardless of the assigned exercise approach , result ing in a 3.3 % ( 95 % CI : 1.1 to 5.5 % ) decrease over two years ( numbers needed to treat ( NNT ) = 30.3 , 95 % CI = 18.2 to 90.9 ) . Conclusions Core stabilization has been advocated as preventative , but offered no such benefit when compared to traditional lumbar exercise in this trial . Instead , a brief psychosocial education program that reduced fear and threat of low back pain decreased incidence of low back pain result ing in the seeking of health care . Since this trial was conducted in a military setting , future studies are necessary to determine if these findings can be translated into civilian population s . Trial Registration NCT00373009 at Clinical Trials.gov - http:// clinical Background Low back pain ( LBP ) is a prevalent and costly condition in the United States . Evidence suggests there is no one treatment which is best for all patients , but instead several viable treatment options . Additionally , multidisciplinary management of LBP may be more effective than monodisciplinary care . An integrative model that includes both complementary and alternative medicine ( CAM ) and conventional therapies , while also incorporating patient choice , has yet to be tested for chronic LBP.The primary aim of this study is to determine the relative clinical effectiveness of 1 ) monodisciplinary chiropractic care and 2 ) multidisciplinary integrative care in 200 adults with non-acute LBP , in both the short-term ( after 12 weeks ) and long-term ( after 52 weeks ) . The primary outcome measure is patient-rated back pain . Secondary aims compare the treatment approaches in terms of frequency of symptoms , low back disability , fear avoidance , self-efficacy , general health status , improvement , satisfaction , work loss , medication use , lumbar dynamic motion , and torso muscle endurance . Patients ' and providers ' perceptions of treatment will be described using qualitative methods , and cost-effectiveness and cost utility will be assessed . Methods and Design This paper describes the design of a r and omized clinical trial ( RCT ) , with cost-effectiveness and qualitative studies conducted alongside the RCT . Two hundred participants ages 18 and older are being recruited and r and omized to one of two 12-week treatment interventions . Patient-rated outcome measures are collected via self-report question naires at baseline , and at 4 , 12 , 26 , and 52 weeks post-r and omization . Objective outcome measures are assessed at baseline and 12 weeks by examiners blinded to treatment assignment . Health care cost data is collected by self-report question naires and treatment records during the intervention phase and by monthly phone interviews thereafter . Qualitative interviews , using a semi-structured format , are conducted with patients at the end of the 12-week treatment period and also with providers at the end of the trial . Discussion This mixed- methods r and omized clinical trial assesses clinical effectiveness , cost-effectiveness , and patients ' and providers ' perceptions of care , in treating non-acute LBP through evidence -based individualized care delivered by monodisciplinary or multidisciplinary care teams . Trial registration Clinical Trials.gov Pharmacological therapy of back pain with analgesics and anti-inflammatory drugs is frequently associated with adverse effects , particularly in the elderly . Aim of this study was to compare mesotherapic versus conventional systemic administration of nonsteroidal anti-inflammatory drugs ( NSAIDs ) and corticosteroids in patients with acute low back pain . Eighty-four patients were r and omized to receive anti-inflammatory therapy according to the following protocol s : ( a ) mesotherapy group received the 1st and 4th day 2 % lidocaine ( 1 mL ) + ketoprofen 160 mg ( 1 mL ) + methylprednisolone 40 mg ( 1 mL ) , then on 7th , 10th , and 13th day , 2 % lidocaine ( 1 mL ) + ketoprofen 160 mg ( 1 mL ) + methylprednisolone 20 mg ( 1 mL ) ( b ) conventional therapy group received ketoprofen 80 mg × 2/die and esomeprazole 20 mg/die orally for 12 days , methylprednisolone 40 mg/die intramuscularly for 4 days , followed by methylprednisolone 20 mg/die for 3 days , and thereafter , methylprednisolone 20 mg/die at alternate days . Pain intensity and functional disability were assessed at baseline ( T0 ) , at the end of treatment ( T1 ) , and 6 months thereafter ( T2 ) by using visual analogic scale ( VAS ) and Rol and -Morris disability question naire ( RMDQ ) . In both groups , VAS and RMDQ values were significantly reduced at the end of drug treatment and after 6 months , in comparison with baseline . No significant differences were found between the two groups . This suggests that mesotherapy may be a valid alternative to conventional therapy in the treatment of acute low back pain with corticosteroids and NSAIDs Background and Purpose — We developed a new postdischarge system of care comprising a structured assessment covering longer-term problems experienced by patients with stroke and their carers , linked to evidence -based treatment algorithms and reference guides ( the longer-term stroke care system of care ) to address the poor longer-term recovery experienced by many patients with stroke . Methods — A pragmatic , multicentre , cluster r and omized controlled trial of this system of care . Eligible patients referred to community-based Stroke Care Coordinators were r and omized to receive the new system of care or usual practice . The primary outcome was improved patient psychological well-being ( General Health Question naire-12 ) at 6 months ; secondary outcomes included functional outcomes for patients , carer outcomes , and cost-effectiveness . Follow-up was through self-completed postal question naires at 6 and 12 months . Results — Thirty-two stroke services were r and omized ( 29 participated ) ; 800 patients ( 399 control ; 401 intervention ) and 208 carers ( 100 control ; 108 intervention ) were recruited . In intention to treat analysis , the adjusted difference in patient General Health Question naire-12 mean scores at 6 months was −0.6 points ( 95 % confidence interval , −1.8 to 0.7 ; P=0.394 ) indicating no evidence of statistically significant difference between the groups . Costs of Stroke Care Coordinator inputs , total health and social care costs , and quality -adjusted life year gains at 6 months , 12 months , and over the year were similar between the groups . Conclusions — This robust trial demonstrated no benefit in clinical or cost-effectiveness outcomes associated with the new system of care compared with usual Stroke Care Coordinator practice . Clinical Trial Registration — URL : http://www.controlled-trials.com . Unique identifier : IS RCT N 67932305 OBJECTIVE : To contrast the efficacy of two exercise programs , segmental stabilization and strengthening of abdominal and trunk muscles , on pain , functional disability , and activation of the transversus abdominis muscle ( TrA ) , in individuals with chronic low back pain . DESIGN : Our sample consisted of 30 individuals , r and omly assigned to one of two treatment groups : segmental stabilization , where exercises focused on the TrA and lumbar multifidus muscles , and superficial strengthening , where exercises focused on the rectus abdominis , abdominus obliquus internus , abdominus obliquus externus , and erector spinae . Groups were examined to discovere whether the exercises created contrasts regarding pain ( visual analogical scale and McGill pain question naire ) , functional disability ( Oswestry disability question naire ) , and TrA muscle activation capacity ( Pressure Biofeedback Unit = PBU ) . The program lasted 6 weeks , and 30‐minute sessions occurred twice a week . Analysis of variance was used for inter‐ and intra‐group comparisons . The significance level was established at 5 % . RESULTS : As compared to baseline , both treatments were effective in relieving pain and improving disability ( p<0.001 ) . Those in the segmental stabilization group had significant gains for all variables when compared to the ST group ( p<0.001 ) , including TrA activation , where relative gains were 48.3 % and ‐5.1 % , respectively . CONCLUSION : Both techniques lessened pain and reduced disability . Segmental stabilization is superior to superficial strengthening for all variables . Superficial strengthening does not improve TrA activation capacity Background Active approaches including both specific and unspecific exercise are probably the most widely recommended treatment for patients with chronic low back pain but it is not known exactly which types of exercise provide the most benefit . Nordic Walking - power walking using ski poles - is a popular and fast growing type of exercise in Northern Europe that has been shown to improve cardiovascular metabolism . Until now , no studies have been performed to investigate whether Nordic Walking has beneficial effects in relation to back pain . Methods A total of 151 patients with low back and /or leg pain of greater than eight weeks duration were recruited from a hospital based outpatient back pain clinic . Patients continuing to have pain greater than three on the 11-point numeric rating scale after a multidisciplinary intervention were included . Fifteen patients were unable to complete the baseline evaluation and 136 patients were r and omized to receive A ) Nordic walking supervised by a specially trained instructor twice a week for eight weeks B ) One-hour instruction in Nordic walking by a specially trained instructor followed by advice to perform Nordic walking at home as much as they liked for eight weeks or C ) Individual oral information consisting of advice to remain active and about maintaining the daily function level that they had achieved during their stay at the backcenter . Primary outcome measures were pain and disability using the Low Back Pain Rating Scale , and functional limitation further assessed using the Patient Specific Function Scale . Furthermore , information on time off work , use of medication , and concurrent treatment for their low back pain was collected . Objective measurements of physical activity levels for the supervised and unsupervised Nordic walking groups were performed using accelerometers . Data were analyzed on an intention-to-treat basis . Results No mean differences were found between the three groups in relation to any of the outcomes at baseline . For pain , disability , and patient specific function the supervised Nordic walking group generally faired best however no statistically significant differences were found . Regarding the secondary outcome measures , patients in the supervised group tended to use less pain medication , to seek less concurrent care for their back pain , at the eight-week follow-up . There was no difference between physical activity levels for the supervised and unsupervised Nordic walking groups . No negative side effects were reported . Conclusion We did not find statistically significant differences between eight weeks of supervised or unsupervised Nordic walking and advice to remain active in a group of chronic low back pain patients . Nevertheless , the greatest average improvement tended to favor the supervised Nordic walking group and - taking into account other health related benefits of Nordic walking - this form of exercise may potentially be of benefit to selected groups of chronic back pain patients .Trial registration http://www . Clinical Trials.gov # & NA ; Several treatment principles for the reduction of chronic low back pain associated disability have been postulated . To examine whether a combination of a physical training and an operant‐behavioral grade d activity with problem solving training is more effective than either alone in the long‐term , a cluster r and omized controlled trial was conducted . In total 172 patients , 18–65 years of age , with chronic disabling non‐specific low back pain referred for rehabilitation treatment , were r and omized in clusters of four consecutive patients to 10 weeks of aerobic training and muscle strengthening of back extensors ( active physical treatment ; APT ) , 10 weeks of gradual assumption of patient relevant activities based on operant‐behavioral principles and problem solving training ( grade d activity plus problem solving training ; GAP ) , or APT combined with GAP ( combination treatment ; CT ) . The primary outcome was the Rol and Disability Question naire adjusted for centre of treatment , cluster , and baseline scores . Secondary outcomes were patients ’ main complaints , pain intensity , self‐perceived improvement , depression and six physical performance tasks . During the one‐year follow‐up , there were no significant differences between each single treatment and the combination treatment on the primary outcome , the Rol and Disability Question naire . Among multiple other comparisons , only one significant difference emerged , with GAP and APT showing higher self‐perceived improvement than CT . We conclude that the combination treatment integrating physical , grade d activity with problem solving training is not a better treatment option for patients with chronic low back pain Abstract Objective : This multicenter , double-blind , placebo-controlled study using a r and omized withdrawal design evaluated the efficacy and safety of once-daily OROS hydromorphone ER in the treatment of opioid-tolerant patients with chronic moderate-to-severe low back pain ( LBP ) . Main outcome measures : The primary efficacy assessment was mean change in pain intensity based on patient diary Numeric Rating Scale ( NRS ) scores from baseline to final visit of the 12-week double-blind phase . Secondary endpoints included mean change from baseline to each visit in patient diary NRS scores ; and office NRS scores ; time to treatment failure ; Patient Global Assessment ; rescue medication use ; and Rol and Morris Disability Question naire total scores . Clinical Trial Registration : Trial registration : Clinical Trials.gov identifier : NCT00549042 . Results : For the primary outcome measure , hydromorphone ER significantly reduced pain intensity compared to placebo ( p < 0.001 ) . Median diary NRS score change from baseline to endpoint was significantly lower for hydromorphone ER ( 0.2 units ) compared to placebo ( 1.2 units ) . A significantly higher proportion of hydromorphone ER ( 60.6 % ) vs. placebo ( 42.9 % ) patients had at least a 30 % reduction in diary NRS pain score from screening to endpoint ( p < 0.01 ) . Hydromorphone ER was well-tolerated , although 60 ( 13 % ) discontinued during the enrichment phase for adverse events and more active ( 9 , 6.7 % ) than placebo ( 4 , 3.0 % ) patients discontinued treatment for adverse events during the r and omized phase . Conclusions : These results provide evidence for the efficacy and safety of hydromorphone ER in opioid-tolerant patients with chronic moderate-to-severe LBP . Potential limitations include the shortened dose-conversion/titration phase , limiting the daily allowable dose of hydromorphone ER to 64 mg , and the allowance of limited rescue medication throughout the entire double-blind phase . Other trial design elements such as the use of an enrichment phase and the inclusion of only opioid tolerant patients may limit the generalizabilty of these results Background Reporting numbers needed to treat ( NNT ) improves interpretability of trial results . It is unusual that continuous outcomes are converted to numbers of individual responders to treatment ( i.e. , those who reach a particular threshold of change ) ; and deteriorations prevented are only rarely considered . We consider how numbers needed to treat can be derived from continuous outcomes ; illustrated with a worked example showing the methods and challenges . Methods We used data from the UK BEAM trial ( n = 1 , 334 ) of physical treatments for back pain ; originally reported as showing , at best , small to moderate benefits . Participants were r and omised to receive ' best care ' in general practice , the comparator treatment , or one of three manual and /or exercise treatments : ' best care ' plus manipulation , exercise , or manipulation followed by exercise . We used established consensus thresholds for improvement in Rol and -Morris disability question naire scores at three and twelve months to derive NNTs for improvements and for benefits ( improvements gained+deteriorations prevented ) . Results At three months , NNT estimates ranged from 5.1 ( 95 % CI 3.4 to 10.7 ) to 9.0 ( 5.0 to 45.5 ) for exercise , 5.0 ( 3.4 to 9.8 ) to 5.4 ( 3.8 to 9.9 ) for manipulation , and 3.3 ( 2.5 to 4.9 ) to 4.8 ( 3.5 to 7.8 ) for manipulation followed by exercise . Corresponding between-group mean differences in the Rol and -Morris disability question naire were 1.6 ( 0.8 to 2.3 ) , 1.4 ( 0.6 to 2.1 ) , and 1.9 ( 1.2 to 2.6 ) points . Conclusion In contrast to small mean differences originally reported , NNTs were small and could be attractive to clinicians , patients , and purchasers . NNTs can aid the interpretation of results of trials using continuous outcomes . Where possible , these should be reported alongside mean differences . Challenges remain in calculating NNTs for some continuous outcomes .Trial Registration UK BEAM trial registration : IS RCT N32683578 Abstract Psychological factors consistent with fear‐avoidance models are associated with the development of chronic low back pain ( LBP ) . As a result , grade d activity ( GA ) and grade d exposure ( GX ) have been suggested as behavioral treatment options . This clinical trial compared the effectiveness of treatment‐based classification ( TBC ) physical therapy alone to TBC augmented with GA or GX for patients with acute and sub‐acute LBP . Our primary hypothesis was that GX would be most effective for those with elevated pain‐related fear . In total , 108 patients enrolled in this clinical trial and were r and omly assigned to receive TBC , GA , or GX . Outcomes were assessed by a blinded evaluator at 4 weeks and by mail at 6 months . The primary outcomes for this trial were disability and pain intensity , and the secondary outcomes were fear‐avoidance beliefs , pain catastrophizing , and physical impairment . There were no differences in 4‐week and 6‐month outcomes for reduction of disability , pain intensity , pain catastrophizing , and physical impairment . GX and TBC were associated with larger reductions in fear‐avoidance beliefs at 6 months only . Six‐month reduction in disability was associated with reduction in pain intensity , while 6‐month reduction in pain intensity was associated with reductions in fear‐avoidance beliefs and pain catastrophizing . This trial suggests that supplementing TBC with GA or GX was not effective for improving important outcomes related to the development of chronic LBP Objective Chronic low back pain ( CLBP ) is a widespread ailment . The aim of this study was to assess the efficacy of topiramate in the treatment of CLBP and the changes in anger status and processing , body weight , subjective pain-related disability and health-related quality of life during the course of treatment . Methods We conducted a 10-week , r and omized , double-blind , placebo-controlled study of topiramate in 96 ( 36 women ) patients with CLBP . The subjects were r and omly assigned to topiramate ( n=48 ) or placebo ( n=48 ) . Primary outcome measures were changes on the McGill Pain Question naire , State-Trait Anger Expression Inventory , Oswestry Low Back Pain Disability Question naire and SF-36 Health Survey scales , and in body weight . Results In comparison with the placebo group ( according to the intent-to-treat principle ) , significant changes on the pain rating index of McGill Pain Question naire ( Ps<0.001 ) , State-Trait Anger Expression Inventory Scales ( all Ps<0.001 ) , Oswestry Low Back Pain Disability Question naire ( P<0.001 ) , and SF-36 Health Survey scales ( all P<0.001 , except on the role-emotional scale ) were observed after 10 weeks in the patients treated with topiramate . Weight loss was also observed and was significantly more pronounced in the group treated with topiramate than in those treated with placebo ( P<0.001 ) . Most patients tolerated topiramate relatively well but 2 patients dropped out because of side effects . Discussion Topiramate seems to be a relatively safe and effective agent in the treatment of CLBP . Significantly positive changes in pain sensitivity , anger status and processing , subjective disability , health-related quality of life , and loss of weight were observed Background Chronic low back pain ( CLBP ) is a persistent disabling condition with rising significant healthcare , social and economic costs . Current research supports the use of exercise-based treatment approaches that encourage people with CLBP to assume a physically active role in their recovery . While international clinical guidelines and systematic review s for CLBP support supervised group exercise as an attractive first-line option for treating large numbers of CLBP patients at low cost , barriers to their delivery include space and time restrictions in healthcare setting s and poor patient attendance . The European Clinical Guidelines have identified the need for research in the use of brief/minimal contact self-activation interventions that encourage participation in physical activity for CLBP . Walking may be an ideally suited form of individualized exercise prescription as it is easy to do , requires no special skills or facilities , and is achievable by virtually all ages with little risk of injury , but its effectiveness for LBP is unproven . Methods and design This study will be an assessor-blinded r and omized controlled trial that will investigate the difference in clinical effectiveness and costs of an individualized walking programme and a supervised general exercise programme compared to usual physiotherapy , which will act as the control group , in people with chronic low back pain . A sample of 246 patients will be recruited in Dublin , Irel and through acute general hospital outpatient physiotherapy departments that provide treatment for people with CLBP . Patients will be r and omly allocated to one of the three groups in a concealed manner . The main outcomes will be functional disability , pain , quality of life , fear avoidance , back beliefs , physical activity , satisfaction and costs , which will be evaluated at baseline , and 3 , 6 and 12 months [ follow-up by pre-paid postage ] . Qualitative telephone interviews and focus groups will be embedded in the research design to obtain feedback about participants ' experiences of the interventions and trial participation , and to inform interpretation of the quantitative data . Planned analysis will be by intention to treat ( quantitative data ) and thematic analysis ( qualitative data ) Discussion The trial will evaluate the effectiveness of a walking programme and a supervised general exercise programme compared to usual physiotherapy in people with CLBP.Trial registration Current controlled trial IS RCT ABSTRACT RotaTeq ( Merck & Co. Inc./Sanofi Pasteur MSD ) is a three-dose , oral pentavalent rotavirus vaccine for the immunization of infants from 6 weeks of age for the prevention of rotavirus gastroenteritis . The primary objective of the present trial was to demonstrate that RotaTeq can be coadministered with meningococcal serogroup C conjugate vaccine ( MenCC ; NeisVac-C ; Baxter Healthcare ) to healthy infants without impairing the protective immune responses to MenCC . This was an open-label , r and omized , comparative study conducted in Finl and . The study was design ed to assess concomitant versus sequential administration of RotaTeq and MenCC on the immune response to both vaccines . Healthy infants ( n = 247 ) , aged 6 to 7 weeks , were recruited . Coadministration of MenCC with RotaTeq was noninferior to sequential administration for the seroprotection rate against meningococcal serogroup C ( the proportion of infants with a serum bactericidal antibody titer using baby rabbit complement of ≥8 was 100 % in both groups ) . The other responses to MenCC ( titer of ≥1:128 , ≥4-fold increase in titer , and geometric mean titers [ GMTs ] ) and the responses to RotaTeq ( IgA and SNA response to G1 to G4 and P1A[8 ] , GMTs , and ≥3-fold increase in titer ) were comparable between groups , including a ≥3-fold IgA increase in > 96 % of the infants in both groups . Concomitant administration of the first doses of MenCC , diphtheria and tetanus toxoids and acellular pertussis vaccine , inactivated poliovirus vaccine , and Haemophilus influenzae type b conjugate vaccine ( DTaP-IPV-Hib ) , and RotaTeq was associated with a higher rate of vomiting and diarrhea than concomitant administration of MenCC and DTaP-IPV-Hib , but that was not observed after the second concomitant administration . The convenience of concomitant administration of RotaTeq and MenCC may , however , outweigh the additive effect of mostly mild adverse events reported after the individual administration of each vaccine . These results support the coadministration of RotaTeq and MenCC The effect of low back pain , with or without nerve root signs , on the joint coordination and kinematics of the lumbar spine and hips during everyday activities , such as picking up an object from the floor , are largely unknown . An experimental study was design ed to compare lumbar spine and hip joint kinematics and coordination in subjects with and without sub-acute low back pain , while picking up an object in a sitting position . A three-dimensional real-time electromagnetic tracking device was used to measure movements of the lumbar spine and hips . Sixty participants with subacute low back pain , with or without straight leg raise signs , and twenty healthy asymptomatic participants were recruited . The ranges of motions of lumbar spine and hips were determined . Movement coordination between the two regions was examined by cross-correlation . Results showed that mobility was significantly reduced in subjects with back pain , who compensated for limited motion through various strategies . The contribution of the lumbar spine relative to that of the hip was , however , found to be similar in all groups . The lumbar spine – hip joint coordination was substantially altered in subjects with back pain , in particular , those with a positive straight leg raise sign . We conclude that changes in the lumbar and hip kinematics were related to back pain and limitation in straight leg raise . Lumbar – hip coordination was mainly affected by the presence of positive straight leg raise sign when picking up an object in a sitting position Study Design . Cluster r and omized clinical trial . Objective . To assess the efficacy of a short education program and short physiotherapy program for treating low back pain ( LBP ) in primary care . Summary of Background Data . There is sparse evidence on the effectiveness of education and physiotherapy programs that are short enough to be feasible in primary care . Methods . Sixty-nine primary care physicians were r and omly assigned to 3 groups and recruited 348 patients consulting for LBP ; 265 ( 79.8 % ) were chronic . All patients received usual care , were given a booklet and received a consistent 15 minutes group talk on health education , which focused on healthy nutrition habits in the control group , and on active management for LBP in the “ education ” and “ education + physiotherapy ” groups . Additionally , in the “ education + physiotherapy ” group , patients were given a second booklet and a 15-minute group talk on postural hygiene , and 4 one-hour physiotherapy sessions of exercise and stretching which they were encouraged to keep practicing at home . The main outcome measure was improvement of LBP-related disability at 6 months . Patients ' assessment and data analyses were blinded . Results . During the 6-month follow-up period , improvement in the “ control ” group was negligible . Additional improvement in the “ education ” and “ education + physiotherapy ” groups was found for disability ( 2.0 and 2.2 Rol and Morris Question naire points , respectively ) , LBP ( 1.8 and 2.10 Visual Analogue Scale points ) , referred pain ( 1.3 and 1.6 Visual Analogue Scale points ) , catastrophizing ( 1.6 and 1.8 Coping Strategies Question naire points ) , physical quality of life ( 2.9 and 2.9 SF-12 points ) , and mental quality of life ( 3.7 and 5.1 SF-12 points ) . Conclusion . The addition of a short education program on active management to usual care in primary care leads to small but consistent improvements in disability , pain , and quality of life . The addition of a short physiotherapy program composed of education on postural hygiene and exercise intended to be continued at home , increases those improvements , although the magnitude of that increase is clinical ly irrelevant Study Design . R and omized parallel group comparative trial with a 1-year follow-up period . Objective . To compare in a population of patients with chronic low back pain , the effectiveness of a functional restoration program ( FRP ) , including intensive physical training and a multidisciplinary approach , with an outpatient active physiotherapy program at 1-year follow-up . Summary of Background Data . Controlled studies conducted in the United States and in Northern Europe showed a benefit of FRPs , especially on return to work . R and omized studies have compared these programs with st and ard care . A previously reported study presented the effectiveness at 6 months of both functional restoration and active physiotherapy , with a significantly greater reduction of sick-leave days for functional restoration . Methods . A total of 132 patients with low back pain were r and omized to either FRP ( 68 patients ) or active individual therapy ( 64 patients ) . One patient did not complete the FRP ; 19 patients were lost to follow-up ( 4 in the FRP group and 15 in the active individual treatment group ) . The number of sick-leave days in 2 years before the program was similar in both groups ( 180 ± 135.1 days in active individual treatment vs. 185 ± 149.8 days in FRP , P = 0.847 ) . Results . In both groups , at 1-year follow-up , intensity of pain , flexibility , trunk muscle endurance , Dallas daily activities and work and leisure scores , and number of sick-leave days were significantly improved compared with baseline . The number of sick-leave days was significantly lower in the FRP group . Conclusion . Both programs are efficient in reducing disability and sick-leave days . The FRP is significantly more effective in reducing sick-leave days . Further analysis is required to determine if this overweighs the difference in costs of both programs Background Current evidence suggests that spinal manipulative therapy ( SMT ) is effective in the treatment of people with low back pain ( LBP ) ; however , the corresponding mechanisms are unknown . Hypoalgesia is associated with SMT and is suggestive of specific mechanisms . Objective The primary purpose of this study was to assess the immediate effects of SMT on thermal pain perception in people with LBP . A secondary purpose was to determine whether the result ing hypoalgesia was a local effect and whether psychological influences were associated with changes in pain perception . Design This study was a r and omized controlled trial . Setting A sample of convenience was recruited from community and outpatient clinics . Participants Thirty-six people ( 10 men , 26 women ) currently experiencing LBP participated in the study . The average age of the participants was 32.39 ( SD=12.63 ) years , and the average duration of LBP was 221.79 ( SD=365.37 ) weeks . Intervention and Measurements Baseline demographic and psychological measurements were obtained , followed by quantitative sensory testing to assess temporal summation and Aδ fiber – mediated pain perception . Next , participants were r and omly assigned to ride a stationary bicycle , perform low back extension exercises , or receive SMT . Finally , the same quantitative sensory testing protocol was reassessed to determine the immediate effects of each intervention on thermal pain sensitivity . Results Hypoalgesia to Aδ fiber – mediated pain perception was not observed . Group-dependent hypoalgesia of temporal summation specific to the lumbar innervated region was observed . Pair-wise comparisons indicated significant hypoalgesia in participants who received SMT , but not in those who rode a stationary bicycle or performed low back extension exercises . Psychological factors did not significantly correlate with changes in temporal summation in participants who received SMT . Limitations Only immediate effects of SMT were measured , so the authors are unable to comment on whether the inhibition of temporal summation is a lasting effect . Furthermore , the authors are unable to comment on the relationship between their findings and changes in clinical pain . Conclusions Inhibition of Aδ fiber – mediated pain perception was similar for all groups . However , inhibition of temporal summation was observed only in participants receiving SMT , suggesting a modulation of dorsal horn excitability that was observed primarily in the lumbar innervated area Objective : To evaluate if a comprehensive manual therapy programme reduces sick leave due low back pain and facilitates return to work more than the conventional optimized activating care . Design : A r and omized controlled trial over a 10-week period with a two-year follow-up . Setting : Primary health care and Visby Hospital , Municipality of Gotl and , Sweden . Subjects : One hundred and sixty patients ( 70 women , 90 men , ages 20—55 years ) with acute or subacute low back pain with or without pain radiation into the legs . Interventions : St and ardized optimized activating care ( n = 71 ) versus a comprehensive pragmatic manual therapy programme including specific corticosteroid injections ( n = 89 ) . Main measures : Sick leave measured as net sick leave volume , point prevalence and return to work . Results : After 10 weeks , significantly more manual therapy patients than reference patients had returned to work ( hazards ratio 1.62 , 95 % confidence interval ( CI ) 1.006—2.60 , P<0.05 ) , and among those on sick leave at baseline , significantly fewer were still on sick leave ( 8/58 versus 13/40 , ratio 0.35 , 95 % CI 0.13—0.97 , P<0.05 ) . For all other measures there were inconclusive differences in favour of the manual therapy group . No significant differences remained after two years . Conclusions : The manual therapy programme used in this study decreased sick leave and increased return to work more than the st and ardized optimized activating care only up to 10 weeks but not up to two years Study Design . A r and omized controlled trial . Objective . To investigate feed-forward activation or timing of abdominal muscle activation in response to rapid shoulder flexion after 8 weeks with core stability exercises , sling exercises , or general exercises in chronic nonspecific low back pain ( LBP ) patients . Summary of Background Data . Delayed onset in abdominal muscles has been associated with LBP . Low load exercises to volitionally activate the transversus abdominis were introduced to restore trunk muscle activation deficits . More forceful co-contraction exercises have been advocated by others . This study explored whether abdominal muscle onset changed after low-load core stability exercises , high-load sling exercises , or general exercises . Methods . Subjects ( N = 109 ) with chronic nonspecific LBP of at least 3 months ' duration were r and omly assigned to 8 weekly treatments with low-load core stability exercises , high-load stabilizing exercises in slings , or general exercises in groups . Primary outcome was onset recorded bilaterally by m-mode ultrasound imaging in the deep abdominal muscles in response to rapid shoulder flexion . Results . No or small changes were found in onset after treatment . Baseline adjusted between group differences showed a 15 ms ( 95 % confidence interval [ CI ] , 1–28 ; P = 0.03 ) and a 19 ms ( 95 % CI , 5–33 ; P < 0.01 ) improvement with sling relative to core stability and general exercises , respectively , but on 1 side only . There was no association between changes in pain and onset over the intervention period ( R2 ⩽ 0.02 ) . Conclusion . Abdominal muscle onset was largely unaffected by 8 weeks of exercises in chronic LBP patients . There was no association between change in onset and LBP . Large individual variations in activation pattern of the deep abdominal muscles may justify exploration of differential effects in subgroups of LBP Background Different interventions can reduce the burden of the chronic low back pain . One example is the use of a ' Back School Programme ' . This is a brief therapy that uses a health education method to empower participants through a procedure of assessment , education and skill development . This study aim ed to evaluate to what extent the programme could improve quality of life in those who suffer from the condition . Methods This was a r and omized controlled trial . One-hundred and two female patients with low back pain ( n = 102 ) were r and omly allocated into two groups , matched in terms of age , weight , education , socioeconomic status , occupation and some aspects of risk behavior . Group 1 ( back school group , n = 50 ) but not group 2 ( clinic group , n = 52 ) received the ' Back School Programme ' . Then quality of life using the Short Form Health Survey ( SF-36 ) was assessed at two time points : at baseline and at three months follow-up . The findings were compared both within and between two groups . Results The ' Back School Programme ' was effective in improving patients ' quality of life ; significant differences were found on all eight subscales of the SF-36 for group 1 . In the clinic group ( group 2 ) , improvement was observed on three scales ( bodily pain , vitality and mental health ) but these improvements were less than in group 1 . The mean improvement over all eight subscales of the SF-36 was significantly better for the ' Back School Programme ' group . Conclusion The ' Back School Programme ' is an effective intervention and might improve the quality of life over a period of 3 months in patients who experience chronic low back pain BACKGROUND CONTEXT Evidence -based clinical practice guidelines ( CPGs ) for the management of patients with acute mechanical low back pain ( AM-LBP ) have been defined on an international scale . Multicenter clinical trials have demonstrated that most AM-LBP patients do not receive CPG-based treatments . To date , the value of implementing full and exclusively CPG-based treatment remains unclear . PURPOSE To determine if full CPGs-based study care ( SC ) results in greater improvement in functional outcomes than family physician-directed usual care ( UC ) in the treatment of AM-LBP . STUDY DESIGN / SETTING A two-arm , parallel design , prospect i ve , r and omized controlled clinical trial using blinded outcome assessment . Treatment was administered in a hospital-based spine program outpatient clinic . PATIENT SAMPLE Inclusion criteria included patients aged 19 to 59 years with Quebec Task Force Categories 1 and 2 AM-LBP of 2 to 4 weeks ' duration . Exclusion criteria included " red flag " conditions and comorbidities contraindicating chiropractic spinal manipulative therapy ( CSMT ) . OUTCOME MEASURES PRIMARY OUTCOME improvement from baseline in Rol and -Morris Disability Question naire ( RDQ ) scores at 16 weeks . SECONDARY OUTCOMES improvements in RDQ scores at 8 and 24 weeks ; and in Short Form-36 ( SF-36 ) bodily pain ( BP ) and physical functioning ( PF ) scale scores at 8 , 16 , and 24 weeks . METHODS Patients were assessed by a spine physician , then r and omized to SC ( reassurance and avoidance of passive treatments , acetaminophen , 4 weeks of lumbar CSMT , and return to work within 8 weeks ) , or family physician-directed UC , the components of which were recorded . RESULTS Ninety-two patients were recruited , with 36 SC and 35 UC patients completing all follow-up visits . Baseline prognostic variables were evenly distributed between groups . The primary outcome , the unadjusted mean improvement in RDQ scores , was significantly greater in the SC group than in the UC group ( p=.003 ) . Regarding unadjusted mean changes in secondary outcomes , improvements in RDQ scores were also greater in the SC group at other time points , particularly at 24 weeks ( p=.004 ) . Similarly , improvements in SF-36 PF scores favored the SC group at all time points ; however , these differences were not statistically significant . Improvements in SF-36 BP scores were similar between groups . In repeated- measures analyses , global adjusted mean improvement was significantly greater in the SC group in terms of RDQ ( p=.0002 ) , nearly significantly greater in terms of SF-36 PF ( p=.08 ) , but similar between groups in terms of SF-36 BP ( p=.27 ) . CONCLUSIONS This is the first reported r and omized controlled trial comparing full CPG-based treatment , including spinal manipulative therapy administered by chiropractors , to family physician-directed UC in the treatment of patients with AM-LBP . Compared to family physician-directed UC , full CPG-based treatment including CSMT is associated with significantly greater improvement in condition-specific functioning Abstract Practice guidelines recommend various types of exercise and manipulative therapy for chronic back pain but there have been few head‐to‐head comparisons of these interventions . We conducted a r and omized controlled trial to compare effects of general exercise , motor control exercise and manipulative therapy on function and perceived effect of intervention in patients with chronic back pain . Two hundred and forty adults with non‐specific low back pain ⩾3 months were allocated to groups that received 8 weeks of general exercise , motor control exercise or spinal manipulative therapy . General exercise included strengthening , stretching and aerobic exercises . Motor control exercise involved retraining specific trunk muscles using ultrasound feedback . Spinal manipulative therapy included joint mobilization and manipulation . Primary outcomes were patient‐specific function ( PSFS , 3–30 ) and global perceived effect ( GPE , −5 to 5 ) at 8 weeks . These outcomes were also measured at 6 and 12 months . Follow‐up was 93 % at 8 weeks and 88 % at 6 and 12 months . The motor control exercise group had slightly better outcomes than the general exercise group at 8 weeks ( between‐group difference : PSFS 2.9 , 95 % CI : 0.9–4.8 ; GPE 1.7 , 95 % CI : 0.9–2.4 ) , as did the spinal manipulative therapy group ( PSFS 2.3 , 95 % CI : 0.4–4.2 ; GPE 1.2 , 95 % CI : 0.4–2.0 ) . The groups had similar outcomes at 6 and 12 months . Motor control exercise and spinal manipulative therapy produce slightly better short‐term function and perceptions of effect than general exercise , but not better medium or long‐term effects , in patients with chronic non‐specific back pain Effect of thermal water with high mineral content on clinical parameters and quality of life of patients with chronic low back pain was studied . In this r and omized controlled , single-blind , follow-up study , 60 patients with chronic low back pain were r and omized into two groups . The treatment group received balneotherapy with thermal-mineral water , and the control group bathed in tap water . Changes of the followings were evaluated : visual analogue scale ( VAS ) for pain , range of motion for the lumbar spine , Oswestry index , EuroQol-5D and Short Form-36 question naires . In the treatment group , the mobility of the lumbar spine , the Oswestry index , the VAS scores and the EuroQoL-5D index improved significantly . SF-36 items improved significantly in the treated group compared with baseline except for two parameters . Our study demonstrated the beneficial effect of balneotherapy with thermal mineral versus tap water on clinical parameters , along with improvements in quality of life The general population has a pessimistic view of low back pain ( LBP ) , and evidence -based information has been used to positively influence LBP beliefs in previously reported mass media studies . However , there is a lack of r and omized trials investigating whether LBP beliefs can be modified in primary prevention setting s. This cluster r and omized clinical trial investigated the effect of an evidence -based psychosocial educational program ( PSEP ) on LBP beliefs for soldiers completing military training . A military setting was selected for this clinical trial , because LBP is a common cause of soldier disability . Companies of soldiers ( n = 3,792 ) were recruited , and cluster r and omized to receive a PSEP or no education ( control group , CG ) . The PSEP consisted of an interactive seminar , and soldiers were issued the Back Book for reference material . The primary outcome measure was the back beliefs question naire ( BBQ ) , which assesses inevitable consequences of and ability to cope with LBP . The BBQ was administered before r and omization and 12 weeks later . A linear mixed model was fitted for the BBQ at the 12-week follow-up , and a generalized linear mixed model was fitted for the dichotomous outcomes on BBQ change of greater than two points . Sensitivity analyses were performed to account for drop out . BBQ scores ( potential range : 9–45 ) improved significantly from baseline of 25.6 ± 5.7 ( mean ± SD ) to 26.9 ± 6.2 for those receiving the PSEP , while there was a significant decline from 26.1 ± 5.7 to 25.6 ± 6.0 for those in the CG . The adjusted mean BBQ score at follow-up for those receiving the PSEP was 1.49 points higher than those in the CG ( P < 0.0001 ) . The adjusted odds ratio of BBQ improvement of greater than two points for those receiving the PSEP was 1.51 ( 95 % CI = 1.22–1.86 ) times that of those in the CG . BBQ improvement was also mildly associated with race and college education . Sensitivity analyses suggested minimal influence of drop out . In conclusion , soldiers that received the PSEP had an improvement in their beliefs related to the inevitable consequences of and ability to cope with LBP . This is the first r and omized trial to show positive influence on LBP beliefs in a primary prevention setting , and these findings have potentially important public health implication s for prevention of LBP Background The purpose of the present study was to examine the differential effect of core stability exercise training and conventional physiotherapy regime on altered postural control parameters in patients with chronic low back pain ( CLBP ) . As heterogeneity in CLBP population moderates the effect of intervention on outcomes , in this study , interventions approaches were used based on sub-groups of CLBP . Methods This was an allocation concealed , blinded , sequential and pragmatic control trial . Three groups of participants were investigated during postural perturbations : 1 ) CLBP patients with movement impairment ( n = 15 , MI group ) r and omized to conventional physiotherapy regime 2 ) fifteen CLBP patients with control impairment r and omized to core stability group ( CI group ) and 3 ) fifteen healthy controls ( HC ) . Results The MI group did not show any significant changes in postural control parameters after the intervention period however they improved significantly in disability scores and fear avoidance belief question naire work score ( P < 0.05 ) . The CI group showed significant improvements in Fx , Fz , and My variables ( p < 0.013 , p < 0.006 , and p < 0.002 respectively with larger effect sizes : Hedges 's g > 0.8 ) after 8 weeks of core stability exercises for the adjusted p values . Postural control parameters of HC group were analyzed independently with pre and post postural control parameters of CI and MI group . This revealed the significant improvements in postural control parameters in CI group compared to MI group indicating the specific adaptation to the core stability exercises in CI group . Though the disability scores were reduced significantly in CI and MI groups ( p < 0.001 ) , the post intervention scores between groups were not found significant ( p < 0.288 ) . Twenty percentage absolute risk reduction in flare-up rates during intervention was found in CI group ( 95 % CI : 0.69 - 0.98 ) . Conclusions In this study core stability exercise group demonstrated significant improvements after intervention in ground reaction forces ( Fz , Mz ; g > 0.8 ) indicating changes in load transfer patterns during perturbation similar to HC group . Trial registration UTRN095032158 - Two 6-week studies compared the analgesic efficacy , tolerability and safety of a non-steroidal anti-inflammatory drug ( celecoxib 200 mg twice a day [ bid ] ) and an opioid ( tramadol HCl 50 mg four times a day [ qid ] ) in subjects with chronic low-back pain ( CLBP ) . Successful responders ( primary endpoint ) were defined as subjects completing 6 weeks of treatment and having ≥ 30 % improvement on the Numerical Rating Scale for pain . A total of 796 and 802 subjects were r and omized to treatment in study 1 and study 2 , respectively . A significantly greater percentage of celecoxib-treated subjects were successful responders compared with tramadol HCl-treated subjects ( study 1 : 63.2 % versus 49.9 % , respectively ; study 2 : 64.1 % versus 55.1 % , respectively ) . Fewer adverse events ( AEs ) and serious AEs were reported in the celecoxib-treated group . Overall , celecoxib 200 mg bid was more effective than tramadol HCl 50 mg qid in the treatment of CLBP , with fewer AEs reported Objective To determine the effectiveness of lessons in the Alex and er technique , massage therapy , and advice from a doctor to take exercise ( exercise prescription ) along with nurse delivered behavioural counselling for patients with chronic or recurrent back pain . Design Factorial r and omised trial . Setting 64 general practice s in Engl and . Participants 579 patients with chronic or recurrent low back pain ; 144 were r and omised to normal care , 147 to massage , 144 to six Alex and er technique lessons , and 144 to 24 Alex and er technique lessons ; half of each of these groups were r and omised to exercise prescription . Interventions Normal care ( control ) , six sessions of massage , six or 24 lessons on the Alex and er technique , and prescription for exercise from a doctor with nurse delivered behavioural counselling . Main outcome measures Rol and Morris disability score ( number of activities impaired by pain ) and number of days in pain . Results Exercise and lessons in the Alex and er technique , but not massage , remained effective at one year ( compared with control Rol and disability score 8.1 : massage −0.58 , 95 % confidence interval −1.94 to 0.77 , six lessons −1.40 , −2.77 to −0.03 , 24 lessons −3.4 , −4.76 to −2.03 , and exercise −1.29 , −2.25 to −0.34 ) . Exercise after six lessons achieved 72 % of the effect of 24 lessons alone ( Rol and disability score −2.98 and −4.14 , respectively ) . Number of days with back pain in the past four weeks was lower after lessons ( compared with control median 21 days : 24 lessons −18 , six lessons −10 , massage −7 ) and quality of life improved significantly . No significant harms were reported . Conclusions One to one lessons in the Alex and er technique from registered teachers have long term benefits for patients with chronic back pain . Six lessons followed by exercise prescription were nearly as effective as 24 lessons . Trial registration National Research Register N0028108728 . How does the Alex and er Technique work ? What are the authors findings about the clinical and cost effectiveness of the treatment ? Watch this video to find out ( 12 mins ) . The aim of this clinical trial was to evaluate the effects of electrical stimulation ( ES ) program on trunk muscle strength , functional performance , quality of life ( QOL ) in the patients with chronic low back pain ( CLBP ) . A total of 41 patients with definite CLBP were included in this study . These patients were r and omized into two groups . Group 1 ( n = 21 ) was given an ES program and exercises . Group 2 ( n = 20 ) was accepted as the control group and given only exercises . Both the programs were performed 3 days a week , for 8 weeks in the out-patient department . The patients were evaluated according to pain , disability , functional performance , endurance , quality of life , depression . The muscle strengths were measured with a h and -held dynamometer . There were significant improvements for all the parameters in two groups after the treatment . Except depression and social function , the improvements for all the parameters were better in the ES group than in the control group . We observed that ES program was very effective in improving QOL , functional performance and isometric strength . In conclusion , we can say that ES therapy provides comfortable life functions by improving muscle strength , functional performance and QOL Objective Chronic low back pain represents a substantial cost to employers through benefits coverage and days missed due to incapacity . We sought to explore the effectiveness of Naturopathic care on chronic low back pain . Methods This study was a r and omized clinical trial . We r and omized 75 postal employees with low back pain of longer than six weeks duration to receive Naturopathic care ( n = 39 ) or st and ardized physiotherapy ( n = 36 ) over a period of 12 weeks . The study was conducted in clinics on-site in postal outlets . Participants in the Naturopathic care group received dietary counseling , deep breathing relaxation techniques and acupuncture . The control intervention received education and instruction on physiotherapy exercises using an approved education booklet . We measured low back pain using the Oswestry disability question naire as the primary outcome measure , and quality of life using the SF-36 in addition to low back range of motion , weight loss , and Body Mass Index as secondary outcomes . Results Sixty-nine participants ( 92 % ) completed eight weeks or greater of the trial . Participants in the Naturopathic care group reported significantly lower back pain ( −6.89 , 95 % CI . −9.23 to −3.54 , p = < 0.0001 ) as measured by the Oswestry question naire . Quality of life was also significantly improved in the group receiving Naturopathic care in all domains except for vitality . Differences for the aggregate physical component of the SF-36 was 8.47 ( 95 % CI , 5.05 to 11.87 , p = < 0.0001 ) and for the aggregate mental component was 7.0 ( 95 % CI , 2.25 to 11.75 , p = 0.0045 ) . All secondary outcomes were also significantly improved in the group receiving Naturopathic care : spinal flexion ( p<0.0001 ) , weight-loss ( p = 0.0052 ) and Body Mass Index ( −0.52 , 95 % CI , −0.96 to −0.08 , p = 0.01 ) . Conclusions Naturopathic care provided significantly greater improvement than physiotherapy advice for patients with chronic low back pain . Trial Registration Controlled-Trials.com IS RCT Background Low back pain is a highly prevalent and disabling condition worldwide . Clinical guidelines for the management of patients with acute low back pain recommend first-line treatment consisting of advice , reassurance and simple analgesics . Exercise is also commonly prescribed to these patients . The primary aim of this study was to evaluate the short-term effect of adding the McKenzie method to the first-line care of patients with acute low back pain . Methods A multi-centre r and omized controlled trial with a 3-month follow-up was conducted between September 2005 and June 2008 . Patients seeking care for acute non-specific low back pain from primary care medical practice s were screened . Eligible participants were assigned to receive a treatment programme based on the McKenzie method and first-line care ( advice , reassurance and time-contingent acetaminophen ) or first-line care alone , for 3 weeks . Primary outcome measures included pain ( 0 - 10 Numeric Rating Scale ) over the first seven days , pain at 1 week , pain at 3 weeks and global perceived effect ( -5 to 5 scale ) at 3 weeks . Treatment effects were estimated using linear mixed models . Results One hundred and forty-eight participants were r and omized into study groups , of whom 138 ( 93 % ) completed the last follow-up . The addition of the McKenzie method to first-line care produced statistically significant but small reductions in pain when compared to first-line care alone : mean of -0.4 points ( 95 % confidence interval , -0.8 to -0.1 ) at 1 week , -0.7 points ( 95 % confidence interval , -1.2 to -0.1 ) at 3 weeks , and -0.3 points ( 95 % confidence interval , -0.5 to -0.0 ) over the first 7 days . Patients receiving the McKenzie method did not show additional effects on global perceived effect , disability , function or on the risk of persistent symptoms . These patients sought less additional health care than those receiving only first-line care ( P = 0.002 ) . Conclusions When added to the currently recommended first-line care of acute low back pain , a treatment programme based on the McKenzie method does not produce appreciable additional short-term improvements in pain , disability , function or global perceived effect . However , the McKenzie method seems to reduce health utilization although it does not reduce patient 's risk of developing persistent symptoms . Trial Registration Australian New Zeal and Clinical Trials Registry : Many manual therapists assess and treat spinal stiffness of people with low back pain . The objectives of this study were to investigate : ( i ) whether spinal stiffness changes after treatment ; ( ii ) the relationship between pre-treatment spinal stiffness and change in stiffness with treatment ; ( iii ) the relationship between spinal stiffness , pain , disability and global perceived effect of treatment ; ( iv ) whether spinal stiffness predicts outcome of treatment or response to treatment in chronic low back pain patients . One hundred and ninety-one subjects with chronic low back pain were r and omly allocated to groups that received either spinal manipulative therapy , motor control exercise , or a general exercise program . Spinal stiffness was assessed before and after intervention . All three groups showed a significant decrease in stiffness following treatment ( p<0.001 ) . No difference between groups was observed . There was a significant negative correlation between pre-treatment stiffness and change in stiffness ( r=-0.61 ; p<0.001 ) . There was a significant but weak correlation ( r=0.18 ; p=0.02 ) between change in stiffness and change in global perceived effect of treatment , and a significant but weak correlation between change in stiffness and change in function for subjects in the spinal manipulative therapy group ( r=-0.28 ; p=0.02 ) . No significant association was observed between initial stiffness score and any of the final outcome measures following treatment . Initial stiffness did not predict response to any treatment . In conclusion , spinal stiffness decreases over the course of an episode of treatment , more so in those with the stiffest spines , but the decrease is not dependent on treatment and is not generally related to outcome Study Design . A r and omized controlled study with 12 months intervention . Objective . To study the effectiveness of a training intervention with emphases on the control of lumbar neutral zone ( NZ ) and behavior modeling as secondary prevention of low back pain ( LBP ) and disability . Summary of Background Data . Improving the control of lumbar NZ and enhancing muscle activation patterns ensuring spinal stability have been proposed as means for secondary prevention of LBP and disability . In addition , cognitive behavior interventions have been shown to lower the risk of recurrence of LBP and long-term disability . Methods . Middle-aged working men with recent LBP but without severe disability were r and omly allocated to either a training ( TG , n = 52 ) or control group ( CG , n = 54 ) . The aim was to exercise twice a week for 12 months , once guided and once independently . The outcome measures were the changes in intensity of LBP , disability , self-evaluated future work ability , and neuromuscular fitness . Results . The intensity of LBP decreased significantly more ( 39 % ) in the TG than in CG at 12 months . The proportion of subjects with negative expectations about their future work ability decreased in both groups at 6 and 12 months ; however , the proportion was significantly bigger in TG compared with CG ( P = 0.028 ) . There effects on disability indexes and fitness were not statistically significant . Conclusions . Controlling lumbar NZ is a specific form of exercise and daily self-care with potential for prevention of recurrent nonspecific LBP and disability among middle aged working men OBJECTIVE To evaluate the effectiveness of specific lumbar extensor training compared with regular physical therapy ( PT ) in workers with nonspecific nonacute low back pain ( LBP ) . DESIGN A multicenter r and omized controlled trial with 1-year follow-up . SETTING PT department in ( military primary care ) health centers . PARTICIPANTS Predominantly male soldiers ( N=129 ) with 4 weeks or more of low back complaints who were referred by the health center 's general practitioner for PT ( mean age , 35.9+/-10.8 y ; range , 20 - 56 y ) , of whom 127 r and omized participants were included in the analyses . One patient withdrew because of adverse effects during treatment . INTERVENTIONS Participants were assigned to 1 of 2 treatment programs : ( 1 ) a 10-week device-supported isolated lumbar extension training , twice a week , or ( 2 ) regular PT , mainly consisting of exercise therapy and aerobic activities . MAIN OUTCOME MEASURES Functional status ( Rol and -Morris Disability Question naire , Patient-Specific Functional Scale ) and global perceived effect were assessed in the short term ( 5 wk , 10 wk ) and long term ( 6 mo , 12 mo ) . RESULTS Both groups showed a favorable development in main outcomes over time : short-term improvements ( after 10 weeks of treatment ) remained stable or even slightly increased throughout the 12-month follow-up . No significant differences between the 2 groups were shown for any of the outcome measures , at any time . CONCLUSIONS Consistent with prior evidence , specific back strengthening does not seem to offer incremental benefits in LBP management compared with regular PT care that mainly consists of general exercise therapy . ( IS RCT N identifier IS RCT N19334317 . Objective An economic evaluation of therapeutic massage , exercise , and lessons in the Alex and er technique for treating persistent back pain . Design Cost consequences study and cost effectiveness analysis at 12 month follow-up of a factorial r and omised controlled trial . Participants 579 patients with chronic or recurrent low back pain recruited from primary care . Interventions Normal care ( control ) , massage , and six or 24 lessons in the Alex and er technique . Half of each group were r and omised to a prescription for exercise from a doctor plus behavioural counselling from a nurse . Main outcome measures Costs to the NHS and to participants . Comparison of costs with Rol and -Morris disability score ( number of activities impaired by pain ) , days in pain , and quality adjusted life years ( QALYs ) . Comparison of NHS costs with QALY gain , using incremental cost effectiveness ratios and cost effectiveness acceptability curves . Results Intervention costs ranged from £ 30 for exercise prescription to £ 596 for 24 lessons in Alex and er technique plus exercise . Cost of health services ranged from £ 50 for 24 lessons in Alex and er technique to £ 124 for exercise . Incremental cost effectiveness analysis of single therapies showed that exercise offered best value ( £ 61 per point on disability score , £ 9 per additional pain-free day , £ 2847 per QALY gain ) . For two-stage therapy , six lessons in Alex and er technique combined with exercise was the best value ( additional £ 64 per point on disability score , £ 43 per additional pain-free day , £ 5332 per QALY gain ) . Conclusions An exercise prescription and six lessons in Alex and er technique alone were both more than 85 % likely to be cost effective at values above £ 20 000 per QALY , but the Alex and er technique performed better than exercise on the full range of outcomes . A combination of six lessons in Alex and er technique lessons followed by exercise was the most effective and cost effective option . How does the Alex and er Technique work ? What are the authors findings about the clinical and cost effectiveness of the treatment ? Watch this video to find out ( 12 mins ) . Background The treatment of non-specific chronic low back pain is often based on three different models regarding the development and maintenance of pain and especially functional limitations : the deconditioning model , the cognitive behavioral model and the biopsychosocial model . There is evidence that rehabilitation of patients with chronic low back pain is more effective than no treatment , but information is lacking about the differential effectiveness of different kinds of rehabilitation . A direct comparison of a physical , a cognitive-behavioral treatment and a combination of both has never been carried out so far . Methods The effectiveness of active physical , cognitive-behavioral and combined treatment for chronic non-specific low back pain compared with a waiting list control group was determined by performing a r and omized controlled trial in three rehabilitation centers . Two hundred and twenty three patients were r and omized , using concealed block r and omization to one of the following treatments , which they attended three times a week for 10 weeks : Active Physical Treatment ( APT ) , Cognitive-Behavioral Treatment ( CBT ) , Combined Treatment of APT and CBT ( CT ) , or Waiting List ( WL ) . The outcome variables were self-reported functional limitations , patient 's main complaints , pain , mood , self-rated treatment effectiveness , treatment satisfaction and physical performance including walking , st and ing up , reaching forward , stair climbing and lifting . Assessment s were carried out by blinded research assistants at baseline and immediately post-treatment . The data were analyzed using the intention-to-treat principle . Results For 212 patients , data were available for analysis . After treatment , significant reductions were observed in functional limitations , patient 's main complaints and pain intensity for all three active treatments compared to the WL . Also , the self-rated treatment effectiveness and satisfaction appeared to be higher in the three active treatments . Several physical performance tasks improved in APT and CT but not in CBT . No clinical ly relevant differences were found between the CT and APT , or between CT and CBT . Conclusion All three active treatments were effective in comparison to no treatment , but no clinical ly relevant differences between the combined and the single component treatments were found Objectives . Newly developed bidirectional modulated sine waves ( BMW ) might provide some derived benefit to patients with low back pain . Pain relief by transcutaneous electric nerve stimulation ( TENS ) with BMWs was tested . Material s and Methods . Analgesic effects of BMWs and conventional bidirectional pulsed waves on chronic back pain in 28 patients were compared , and effects of repeated TENS using BMWs on chronic back pain were investigated in 21 patients by means of a r and omized double-blind , sham-controlled , parallel-group method . Pain intensity was assessed using numerical rating scale ( NRS ) . Results . There was significant immediate reduction in NRS in patients receiving BMWs , and 60 min after treatment compared to sham TENS . Weekly repeated treatments using massage and TENS with BMWs for 5 weeks result ed in a decrease of NRS , but there were no significant differences between the TENS plus massage and sham TENS plus massage groups . Conclusions . This study shows that TENS with BMWs significantly inhibits chronic back pain , and treatment effects are attained within a day . The results also suggest that there were no statistically significant long-term effects of TENS with BMW in the repeated treatment Background The efficacy and safety of the association of celecoxib [ a selective cyclooxygenase-2 ( COX-2 ) inhibitor ] and pregabalin ( commonly used to control neuropathic pain ) , compared with monotherapy of each , were evaluated for the treatment of chronic low-back pain , a condition known to be due to neuropathic as well as nociceptive pain mechanisms . Material s and methods In this prospect i ve r and omized trial , 36 patients received three consecutive 4-week treatment regimes , r and omly assigned : celecoxib plus placebo , pregabalin plus placebo , and celecoxib plus pregabalin . All patients were assessed by using a visual analogue scale ( VAS , 0–100 mm ) and the Leeds Assessment of Neuropathic Symptoms and Signs ( LANSS ) pain scale by an investigator blinded to the administered pharmacological treatment . Results Celecoxib and pregabalin were effective in reducing low-back pain when patients were pooled according to LANSS score . The association of celecoxib and pregabalin was more effective than either monotherapy in a mixed population of patients with chronic low-back pain and when data were pooled according to LANSS score . Adverse effects of drug association and monotherapies were similar , with reduced drug consumption in the combined therapy . Conclusions Combination of celecoxib and pregabalin is more effective than monotherapy for chronic low-back pain , with similar adverse effects UNLABELLED Opioid-experienced ( N = 250 ) patients with chronic , moderate to severe low back pain ( LBP ) were converted from their pre study opioid(s ) to an approximately equianalgesic dose of OPANA ER ( oxymorphone extended release ) . Patients continued slow titration , with 56 % stabilized within 1 month to a dose of OPANA ER that reduced average pain to < 40 mm on a visual analog scale with good tolerability . Stabilized patients ( n = 143 ) were r and omized to placebo or their stabilized dose of OPANA ER every 12 hours for a 12-week double-blind period . Pain intensity increased significantly more for patients r and omized to placebo than for patients who continued their stabilized dose of OPANA ER ; the increase from baseline ( at r and omization ) to final visit was 31.6 mm for placebo versus 8.7 mm with OPANA ER ( P < .0001 ) . During double-blind treatment , placebo patients were approximately 8-fold more likely than OPANA ER patients to discontinue because of lack of efficacy ( P < .001 ) . Discontinuations as a result of adverse events were similar between groups , 10 % with placebo and 11 % with OPANA ER . Opioid-related adverse events included constipation ( 6 % ) , somnolence ( 3 % ) , and nausea ( 3 % ) . Fifty-seven percent of opioid-experienced patients with chronic , moderate to severe LBP achieved a stable dose of OPANA ER that was efficacious and generally well-tolerated for up to 12 weeks . PERSPECTIVE In a 12-week , double-blind , r and omized , placebo-controlled trial in opioid-experienced patients with chronic , moderate to severe LBP , OPANA ER provided efficacious , long-term analgesia and was generally well-tolerated . OPANA ER may provide clinicians with a new treatment option for patients experiencing suboptimal analgesic responses or poor tolerability with other opioids Objective To evaluate the effectiveness of an integrated care programme , combining a patient directed and a workplace directed intervention , for patients with chronic low back pain . Design Population based r and omised controlled trial . Setting Primary care ( 10 physiotherapy practice s , one occupational health service , one occupational therapy practice ) and secondary care ( five hospitals ) . Participants 134 adults aged 18 - 65 sick listed for at least 12 weeks owing to low back pain . Intervention Patients were r and omly assigned to usual care ( n=68 ) or integrated care ( n=66 ) . Integrated care consisted of a workplace intervention based on participatory ergonomics , involving a supervisor , and a grade d activity programme based on cognitive behavioural principles . Main outcome measures The primary outcome was the duration of time off work ( work disability ) due to low back pain until full sustainable return to work . Secondary outcome measures were intensity of pain and functional status . Results The median duration until sustainable return to work was 88 days in the integrated care group compared with 208 days in the usual care group ( P=0.003 ) . Integrated care was effective on return to work ( hazard ratio 1.9 , 95 % confidence interval 1.2 to 2.8 , P=0.004 ) . After 12 months , patients in the integrated care group improved significantly more on functional status compared with patients in the usual care group ( P=0.01 ) . Improvement of pain between the groups did not differ significantly . Conclusion The integrated care programme substantially reduced disability due to chronic low back pain in private and working life . Trial registration Current Controlled Trials IS RCT N28478651 Background : Single-photon emission computed tomography ( SPECT ) is useful in identifying patients who may respond to lumbar facet injections . There are two methods for performing lumbar facet joint injections : intraarticular and medial branch nerve blocks . A consensus has yet to be reached among physicians as to which method is the most effective . The purpose of this study was to compare the effectiveness of intraarticular and medial branch nerve blocks in SPECT-positive lumbar facet joint patients with nonradicular lower back pain . Method : This study was a prospect i ve , double-blinded outcome study of 12 weeks ’ duration . Forty-six male ( 26 ) and female patients ( 20 ) between the ages of 18 and 55 ( mean 39.3 years ) with nonradicular lower back pain who were lumbar facet joint SPECT-positive were studied . No patient was included in this study if magnetic resonance imaging evidence of a lumbar disc herniation was present . Patients were r and omly assigned by computer to have intraarticular ( group I ) or medial branch nerve blocks ( group II ) with lidocaine and triamcinolone , with 23 patients in each group . Outcome measurements assessed the Numeric Pain Intensity Scores ( NPIS 0–10 ) and the Oswestry Disability Index scores ( ODI 0–50 ) . Results : There were no differences in demographics between the two groups . The percentage of pain relief ( 61 % ) and the percentage of disability ( 53 % ) reduction were significantly greater ( P < 0.05 ) in group I when compared to group II ( 26 % and 31 % respectively ) . Conclusions : Intraarticular lumbar facet joint injections are more effective than medial branch nerve blocks in SPECT-positive patients BACKGROUND CONTEXT Several conservative therapies have been shown to be beneficial in the treatment of chronic low back pain ( CLBP ) , including different forms of exercise and spinal manipulative therapy ( SMT ) . The efficacy of less time-consuming and less costly self-care interventions , for example , home exercise , remains inconclusive in CLBP population s. PURPOSE The purpose of this study was to assess the relative efficacy of supervised exercise , spinal manipulation , and home exercise for the treatment of CLBP . STUDY DESIGN / SETTING An observer-blinded and mixed- method r and omized clinical trial conducted in a university research clinic in Bloomington , MN , USA . PATIENT SAMPLE Individuals , 18 to 65 years of age , who had a primary complaint of mechanical LBP of at least 6-week duration with or without radiating pain to the lower extremity were included in this trial . OUTCOME MEASURES Patient-rated outcomes were pain , disability , general health status , medication use , global improvement , and satisfaction . Trunk muscle endurance and strength were assessed by blinded examiners , and qualitative interviews were performed at the end of the 12-week treatment phase . METHODS This prospect i ve r and omized clinical trial examined the short- ( 12 weeks ) and long-term ( 52 weeks ) relative efficacy of high-dose , supervised low-tech trunk exercise , chiropractic SMT , and a short course of home exercise and self-care advice for the treatment of LBP of at least 6-week duration . The study was approved by local institutional review boards . RESULTS A total of 301 individuals were included in this trial . For all three treatment groups , outcomes improved during the 12 weeks of treatment . Those who received supervised trunk exercise were most satisfied with care and experienced the greatest gains in trunk muscle endurance and strength , but they did not significantly differ from those receiving chiropractic spinal manipulation or home exercise in terms of pain and other patient-rated individual outcomes , in both the short- and long-term . CONCLUSIONS For CLBP , supervised exercise was significantly better than chiropractic spinal manipulation and home exercise in terms of satisfaction with treatment and trunk muscle endurance and strength . Although the short- and long-term differences between groups in patient-rated pain , disability , improvement , general health status , and medication use consistently favored the supervised exercise group , the differences were relatively small and not statistically significant for these individual outcomes Our aim is to investigate the effects of three therapeutic approaches in the chronic low back pain on pain , spinal mobility , disability , psychological state , and aerobic capacity . Sixty patients with chronic low back pain were r and omized to three groups : group 1 , aerobic exercise + home exercise ; group 2 , physical therapy ( hot pack , ultrasound , TENS ) + home exercise ; group 3 , home exercise only . Spinal mobility , pain severity , disability , and psychological disturbance of the patients were assessed before and after the treatment and at 1-month follow-up . Aerobic capacities of the patients were measured before and after treatment . All of the groups showed similar decrease in pain after the treatment and at 1-month follow-up , and there was no significant difference between the groups . In group 2 , a significant decrease in Beck Depression Inventory scores was observed with treatment . At 1-month follow-up , group 1 and 2 showed significant decreases in General Health Assessment Question naire scores . In group 2 , there was also a significant improvement in Rol and Morris Disability scores . There were similar improvements in exercise test duration and the MET levels in all the three groups . All of the three therapeutic approaches were found to be effective in diminishing pain and thus increasing aerobic capacity in patients with chronic low back pain . On the other h and , physical therapy + home exercise was found to be more effective regarding disability and psychological disturbance The present study has been conducted to evaluate selected yogic procedures on individuals with low back pain . The underst and ing of back pain as one of the commonest clinical presentations during clinical practice made the path to the present study . It has also been calculated that more than three-quarters of the world 's population experience back pain at some time in their lives . Twelve patients were selected and r and omly divided into two groups , viz . , group A yogic group and group B control group . Advice for life style and diet was given for all the patients . The effect of the therapy was assessed subjectively and objective ly . Particular scores drawn for yogic group and control group were individually analyzed before and after treatment and the values were compared using st and ard statistical protocol s. Yogic intervention revealed 79 % relief in both subjective and objective parameters ( i.e. , 7 out of 14 parameters showed statistically highly significant P < 0.01 results , while 4 showed significant results P < 0.05 ) . Comparative effect of yogic group and control group showed 79 % relief in both subjective and objective parameters . ( i.e. , total 6 out of 14 parameters showed statistically highly significant ( P < 0.01 ) results , while 5 showed significant results ( P < 0.05 ) STUDY DESIGN R and omized clinical trial . OBJECTIVES To determine the efficacy of trunk balance exercises for individuals with chronic low back pain . BACKGROUND The majority of exercises focusing on restoring lumbopelvic stability propose targeting the feedforward control of the lumbopelvic region . Less attention has been paid to feedback control during balance adjustments . METHODS Seventy-nine patients were r and omly allocated to 2 different groups . The experimental group performed trunk balance exercises in addition to st and ard trunk flexibility exercises . The control group performed strengthening exercises in addition to the same st and ard trunk flexibility exercises . The primary outcome measures were pain intensity ( visual analogue scale ) , disability ( Rol and -Morris Question naire ) , and quality of life ( 12-Item Short-Form Health Survey ) . Secondary outcomes were painful positions , use of analgesic drugs , and referred pain . Analysis of variance and relative risk were used to analyze the data for the primary and secondary outcome measures , respectively . The number of participants reaching the minimal clinical ly important difference in the 2 groups for each outcome measure was compared using relative risk . RESULTS A significant difference in scores on the Rol and -Morris Question naire ( P = .011 ) and the physical component of the 12-Item Short-Form Health Survey ( P = .048 ) , and in the number of participants reaching the minimal clinical ly important difference for the Rol and -Morris Question naire ( relative risk , 1.79 ; 95 % confidence interval [ CI ] : 1.05 , 3.04 ) and the secondary outcome of painful positions ( relative risk , 1.37 ; 95 % CI : 1.03 , 1.83 ) were found in favor of the experimental treatment . CONCLUSIONS Trunk balance exercises combined with flexibility exercises were found to be more effective than a combination of strength and flexibility exercises in reducing disability and improving the physical component of quality of life in patients with chronic low back pain BACKGROUND In various pain studies , the single-dose combination of paracetamol/tramadol ( PIT ) was found to be more effective than either agent alone . PIT could provide benefit in patients with subacute low back pain ( LBP ) . OBJECTIVE This study compared the efficacy and tolerability of PIT with tramadol alone ( T ) in patients with subacute LBP and assessed whether , under comparable analgesic conditions , PIT would be better tolerated . METHODS This was a multicenter , r and omized , double-blind , parallel-group study . Patients were enrolled if they suffered from nonspecific LBP lasting 10 to 42 days and experienced at least moderate pain ( > or = 40 mm on a 100-mm visual analog scale ) . Patients were r and omized and treated for 10 days with PIT ( 325 mg/37.5 mg ) or T ( 50 mg ) . The study outcomes were treatment efficacy ( pain intensity , pain relief , patient satisfaction , physicians ' assessment of pain control ) and tolerability ( adverse events [ AEs ] , patients ' tolerability judgment ) . RESULTS A total of 119 patients were enrolled ( PIT , n = 59 ; T , n = 60 ) . Demographic characteristics of patients were comparable between the PIT and T groups in regard to age ( mean , 56.5 vs 54.1 years , respectively ) , sex ( women/men , 38121 vs 31129 ) , race ( white , 96.1 % vs 94.2 % ) , and body mass index ( 24.9 vs 26.1 kg/m2 ) . Pain intensity ( mean [ SD ] percentage of worst imaginable pain ) improved from nearly identical levels at baseline ( P/T , 67.5 [ 13.0 ] vs T , 65.3 [ 14.6 ] ; P = NS ) to similarly low levels at the final visit ( P/T , 27.9 [ 22.7 ] vs T , 24.8 [ 21.6 ] ; P = NS ) . The reduction in pain intensity was significant in both treatment groups ( P < 0.001 ) . Adequate pain relief ( ie , " moderate , " " important , " or " complete " ) was observed in 81.6 % ( 40149 ) of PIT patients versus 82.9 % ( 39147 ) of T patients ( P = NS ) . Comparably high rates of overall patient satisfaction ( 72.5 % [ 37151 ] vs 72.9 % [ 35148 ] , respectively ; P = NS ) were achieved . Both treatment groups took a comparable number of daily units of study medication , which result ed in significantly ( P < 0.001 ) lower daily doses of tramadol in the P/T group ( mean [ SD ] , 172.5 [ 46.6 ] mg ) than in the T group ( 227.3 [ 59.7 ] mg ) . More P/T patients ( 84.3 % ) than T patients ( 68.8 % ) judged treatment tolerability as good or very good ( P = NS ) . Significantly fewer AEs ( P < 0.001 ) were observed in PIT patients , and the overall incidence of AEs ( mostly opioid-typical AEs [ eg , nausea , dizziness/vertigo , sleepiness/drowsiness , constipation , vomiting ] ) was much lower after P/T compared with T ( P = 0.019 ) . The most common AEs in the P/T and T groups were nausea ( 8159 vs 21160 patients , respectively ; P = 0.012 ) and dizziness ( 3/59 vs 15/60 patients ; P= 0.006 ) . CONCLUSIONS Tramadol , alone and in combination with paracetamol , provided highly effective analgesia for these patients with subacute LSP However , the combination of PIT , which result ed in 25 % less tramadol than equianalgesic daily doses of T alone , considerably reduced the incidence of AEs and improved tolerability Intensive group training using principles of grade d activity has been proven to be effective in occupational care for workers with chronic low back pain . Objective of the study was to compare the effects of an intensive group training protocol aim ed at returning to normal daily activities and guideline physiotherapy for primary care patients with non-specific chronic low back pain . The study was design ed as pragmatic r and omised controlled trial with a setup of 105 primary care physiotherapists in 49 practice s and 114 patients with non-specific low back pain of more than 12 weeks duration participated in the study . In the intensive group training protocol exercise therapy , back school and operant-conditioning behavioural principles are combined . Patients were treated during 10 individual sessions along 20 group sessions . Usual care consisted of physiotherapy according to the Dutch guidelines for Low Back Pain . Main outcome measures were functional disability ( Rol and Morris disability question naire ) , pain intensity , perceived recovery and sick leave because of low back pain assessed at baseline and after 6 , 13 , 26 and 52 weeks . Both an intention-to-treat analysis and a per- protocol analysis were performed . Multilevel analysis did not show significant differences between both treatment groups on any outcome measures during the complete follow-up period , with one exception . After 26 weeks the protocol group showed more reduction in pain intensity than the guideline group , but this difference was absent after 52 weeks . We finally conclude that an intensive group training protocol was not more effective than usual physiotherapy for chronic low back pain OBJECTIVES To identify characteristics of r and omized controlled trial participants which predict greater benefits from physical treatments for low back pain . If successful , this would allow more appropriate selection of patients for different treatments . METHODS We did a secondary analysis of the UK Back pain Exercise And Manipulation trial ( UK BEAM n = 1334 ) data set to identify baseline characteristics predicting response to manipulation , exercise and manipulation followed by exercise ( combined treatment ) . Rather than simply identifying factors associated with overall outcome , we tested for the statistical significance of the interaction between treatment allocation , baseline characteristics and outcome to identify factors that predicted response to treatment . We also did a post-hoc subgroup analysis to present separate results for trial participants with subacute and chronic low back pain to inform future evidence synthesis . RESULTS Age , work status , age of leaving school , ' pain and disability ' , ' quality of life ' and ' beliefs ' at baseline all predicted overall outcome . None of these predicted response to treatment . In those allocated to combined treatment , there was a suggestion that expecting treatment to be helpful might improve outcome at 1 yr . Episode length at study entry did not predict response to treatment . CONCLUSION Baseline participant characteristics did not predict response to the UK BEAM treatment packages . Using recognized prognostic variables to select patients for different treatment packages , without first demonstrating that these factors affect response to treatment , may be inappropriate . In particular , this analysis suggests that the distinction between subacute and chronic low back pain may not be useful when considering treatment choices Background Although many clinicians believe there are clinical ly important subgroups of persons with " non-specific " low back pain , such subgroups have not yet been clearly identified . As part of a large trial evaluating acupuncture for chronic low back pain , we sought to identify subgroups of participants that were particularly responsive to acupuncture . Methods We performed a secondary analysis of data for the 638 participants in our clinical trial comparing different types of acupuncture to usual care to identify baseline characteristics that predicted responses to individualized , st and ardized , or simulated acupuncture treatments . After identifying factors that predicted improvements in back-related function or symptoms , we determined if these factors were more likely to predict improvement for those receiving the acupuncture treatments than for those receiving usual care . This was accomplished by testing for an interaction between the prognostic factors and treatment group in four models : functional outcomes ( measured by the Rol and -Morris Disability Scale ) at 8 and 52 weeks post-r and omization and symptom outcomes ( measured with a numerical rating scale ) at 8 and 52 weeks . Results Overall , the strongest predictors of improvement in back function and symptoms were higher baseline levels of these measures , receipt of an acupuncture treatment , and non-use of narcotic analgesics . Benefit from acupuncture compared to usual care was greater with worse pre-treatment levels of back dysfunction ( interaction p < 0.004 for the functional outcome , Rol and Morris Disability Scale at 8 weeks ) . No other consistent interactions were observed . Conclusion This secondary analysis found little evidence for the existence of subgroups of patients with chronic back pain that would be especially likely to benefit from acupuncture . However , persons with chronic low back pain who had more severe baseline dysfunction had the most short-term benefit from acupuncture BACKGROUND Acupuncture is widely used by patients with low back pain , although its effectiveness is unclear . We investigated the efficacy of acupuncture compared with minimal acupuncture and with no acupuncture in patients with chronic low back pain . METHODS Patients were r and omized to treatment with acupuncture , minimal acupuncture ( superficial needling at nonacupuncture points ) , or a waiting list control . Acupuncture and minimal acupuncture were administered by specialized acupuncture physicians in 30 outpatient centers , and consisted of 12 sessions per patient over 8 weeks . Patients completed st and ardized question naires at baseline and at 8 , 26 , and 52 weeks after r and omization . The primary outcome variable was the change in low back pain intensity from baseline to the end of week 8 , as determined on a visual analog scale ( range , 0 - 100 mm ) . RESULTS A total of 298 patients ( 67.8 % female ; mean + /- SD age , 59 + /- 9 years ) were included . Between baseline and week 8 , pain intensity decreased by a mean + /- SD of 28.7 + /- 30.3 mm in the acupuncture group , 23.6 + /- 31.0 mm in the minimal acupuncture group , and 6.9 + /- 22.0 mm in the waiting list group . The difference for the acupuncture vs minimal acupuncture group was 5.1 mm ( 95 % confidence interval , -3.7 to 13.9 mm ; P = .26 ) , and the difference for the acupuncture vs waiting list group was 21.7 mm ( 95 % confidence interval , 13.9 - 30.0 mm ; P<.001 ) . Also , at 26 ( P=.96 ) and 52 ( P=.61 ) weeks , pain did not differ significantly between the acupuncture and the minimal acupuncture groups . CONCLUSION Acupuncture was more effective in improving pain than no acupuncture treatment in patients with chronic low back pain , whereas there were no significant differences between acupuncture and minimal acupuncture Study Design . R and omized , single blind , controlled trial . Objective . To determine the efficacy of 2 components of musculoskeletal physiotherapy on chronic low back disorder . Summary of Background Data . Musculoskeletal physiotherapy encompasses many treatment methods , however , manual therapy and exercises to rehabilitate spinal stabilization are the most frequently used . Despite their popularity , scant evidence supports their use on subjects with chronic low back disorder . Methods . A total of 346 subjects were r and omized to manual therapy , a 10-week spinal stabilization rehabilitation program , or a minimal intervention control group . Data were collected at baseline , and 3 , 6 , 12 , and 24 months after intervention . Outcome measures recorded intensity of low back pain , disability , h and icap , medication , and quality of life . There were 4 main variables combined in a primary component analysis to form a single outcome measure ( i.e. , a measure of dysfunction ) . Results . The results indicated statistically significant improvements in favor of the spinal stabilization group at the 6-month stage in pain ( 65.9 % reduction in symptoms ) and dysfunction ( combined mean reduction of 134 , st and ard error 23.84 ) , and at the 1-year stage in medication ( 34.3 % reduction in medication ) , dysfunction ( combined mean reduction of 134 , st and ard error 18.2 ) , and disability ( mean difference in change 15.71 Oswestry Disability Index , 95 % confidence interval 19.3–10.01 ) . Conclusions . As a component of musculoskeletal physiotherapy , the spinal stabilization program is more effective than manually applied therapy or an education booklet in treating chronic low back disorder over time . Both manual therapy and the spinal stabilization program are significantly effective in pain reduction in comparison to an active control . To our knowledge and up until now , this result has not been shown in patients with chronic low back disorder Abstract Chronic low back pain ( CLBP ) in older adults may be disabling and therapeutically challenging , largely because of the inefficacy and /or morbidity associated with traditional pain treatment . We conducted a r and omized controlled trial in 200 men and women ⩾ age 65 with CLBP to evaluate the efficacy of percutaneous electrical nerve stimulation ( PENS ) with and without general conditioning and aerobic exercise ( GCAE ) , for reducing pain and improving physical function . Participants were r and omized to receive ( 1 ) PENS , ( 2 ) control‐PENS ( brief electrical stimulation to control for treatment expectancy ) , ( 3 ) PENS + GCAE , or ( 4 ) control‐PENS + GCAE , twice a week for 6 weeks . All four groups experienced significantly reduced pain ( range −2.3 to −4.1 on the McGill Pain Question naire short form ) , improved self‐reported disability ( range −2.1 to −3.0 on Rol and scale ) and improved gait velocity ( 0.04–0.07 m/s ) , sustained at 6 months . The GCAE groups experienced significantly fewer fear avoidance beliefs immediately post‐intervention and at 6 months than non‐GCAE groups . There were no significant side effects . Since brief electrical stimulation ( i.e. , control‐PENS ) facilitated comparably reduced pain and improved function at 6 months as compared with PENS , the exact dose of electrical stimulation required for analgesia can not be determined . GCAE was more effective than PENS alone in reducing fear avoidance beliefs , but not in reducing pain or in improving physical function QUESTION Is Strain-Counterstrain treatment combined with exercise therapy more effective than exercise alone in reducing levels of pain and disability in people with acute low back pain ? DESIGN R and omised trial with concealed allocation , assessor blinding , and intention-to-treat analysis . PARTICIPANTS 89 ( 55 female ) participants between 18 and 55 years experiencing acute low back pain were r and omised to experimental ( n = 44 ) and control ( n = 45 ) groups . INTERVENTION Participants attended four treatments in two weeks . The experimental group received Strain-Counterstrain treatment and review of st and ardised exercises ( abdominal bracing , knee to chest , and lumbar rotation ) . The control group performed the st and ardised exercises under supervision . Following the intervention period , all participants received exercise progression , manual therapy , and advice . OUTCOME MEASURES The primary outcome was the modified Oswestry low back pain disability question naire , measured at 2 weeks ( ie , end of treatment ) , 6 weeks , and 28 weeks . Secondary outcome measures included the SF-36 , visual analogue scale pain ratings , and a 7-point global rating of change . RESULTS The experimental intervention was not more effective than exercise alone in reducing levels of pain and disability . Mean between-group differences in change from baseline for the Oswestry Disability Index were 0 ( 95 % CI -6 to 7 ) after treatment , -1 ( 95 % CI -7 to 6 ) at 6 weeks , and 2 ( 95 % CI -4 to 8) at 28 weeks . Other outcomes did not differ significantly between groups . CONCLUSION There is no advantage in providing Strain- Counterstrain treatment to patients with acute low back pain , although further studies could examine whether a subset of these patients can benefit from the treatment . TRIAL REGISTRATION ACTRN 12609000084280 In a r and omized controlled trial plus a nonr and omized cohort , the authors investigated the effectiveness and costs of acupuncture in addition to routine care in the treatment of chronic low back pain and assessed whether the effects of acupuncture differed in r and omized and nonr and omized patients . In 2001 , German patients with chronic low back pain were allocated to an acupuncture group or a no-acupuncture control group . Persons who did not consent to r and omization were included in a nonr and omized acupuncture group . All patients were allowed to receive routine medical care in addition to study treatment . Back function ( Hannover Functional Ability Question naire ) , pain , and quality of life were assessed at baseline and after 3 and 6 months , and cost-effectiveness was analyzed . Of 11,630 patients ( mean age=52.9 years ( st and ard deviation , 13.7 ) ; 59 % female ) , 1,549 were r and omized to the acupuncture group and 1,544 to the control group ; 8,537 were included in the nonr and omized acupuncture group . At 3 months , back function improved by 12.1 ( st and ard error ( SE ) , 0.4 ) to 74.5 ( SE , 0.4 ) points in the acupuncture group and by 2.7 ( SE , 0.4 ) to 65.1 ( SE , 0.4 ) points among controls ( difference=9.4 points ( 95 % confidence interval 8.3 , 10.5 ) ; p<0.001 ) . Nonr and omized patients had more severe symptoms at baseline and showed improvements in back function similar to those seen in r and omized patients . The incremental cost-effectiveness ratio was euro10,526 ( euros ) per quality -adjusted life year . Acupuncture plus routine care was associated with marked clinical improvements in these patients and was relatively cost-effective OBJECTIVE To examine the effect of adding aerobic exercise to conventional physiotherapy treatment for patients with chronic low back pain ( LBP ) in reducing pain and disability . DESIGN R and omized controlled trial . SETTING A physiotherapy outpatient setting in Hong Kong . PARTICIPANTS Patients with chronic LBP ( N=46 ) were recruited and r and omly assigned to either a control ( n=22 ) or an intervention ( n=24 ) group . INTERVENTIONS An 8-week intervention ; both groups received conventional physiotherapy with additional individually tailored aerobic exercise prescribed only to the intervention group . MAIN OUTCOME MEASURES Visual analog pain scale , Aberdeen Low Back Pain Disability Scale , and physical fitness measurements were taken at baseline , 8 weeks , and 12 months from the commencement of the intervention . Multivariate analysis of variance was performed to examine between-group differences . RESULTS Both groups demonstrated a significant reduction in pain ( P<.001 ) and an improvement in disability ( P<.001 ) at 8 weeks and 12 months ; however , no differences were observed between groups . There was no significant difference in LBP relapse at 12 months between the 2 groups ( χ(2)=2.30 , P=.13 ) . CONCLUSIONS The addition of aerobic training to conventional physiotherapy treatment did not enhance either short- or long-term improvement of pain and disability in patients with chronic LBP CONTEXT AND OBJECTIVE Transcutaneous electrical nerve stimulation ( TENS ) and interferential current are the most used electrotherapy methods , although there is little scientific evidence to support their use . The aim of this study was to compare the effects of TENS and interferential current among patients with nonspecific chronic low back pain . DESIGN AND SETTING Single-blind r and omized controlled trial in the Department of Physiotherapy , Centro Universitário de Maringá . METHODS One hundred and fifty patients were r and omly divided into three groups : TENS ( group 1 ) , interferential current ( group 2 ) and controls ( group 3 ) . The patients design ated for electrotherapy received ten 30-minute sessions , while the control group remained untreated . All patients and controls were evaluated before and after treatment using a visual analog scale and the McGill Pain and Rol and Morris question naires , and regarding their use of additional medications . RESULTS There was a mean reduction on the visual analog scale of 39.18 mm with TENS , 44.86 mm with interferential current and 8.53 mm among the controls . In the Rol and Morris question naire , group 1 had a mean reduction of 6.59 ; group 2 , 7.20 ; and group 3 , 0.70 points . In group 1 , 84 % of the patients stopped using medications after the treatment ; in group 2 , 75 % ; and in group 3 , 34 % . There was no statistically significant difference between the TENS and interferential current groups ( P > 0.05 ) ; a difference was only found between these groups and the controls ( P < 0.0001 ) . CONCLUSION There was no difference between TENS and interferential current for chronic low back pain treatment . CLINICAL TRIAL REGISTRATION NCT01017913 OBJECTIVE To examine the effects of 2 manual therapy methods compared with one counselling session with a physiotherapist with " advice-only to stay active " for treating low back pain/leg pain and disability . DESIGN A r and omized , controlled trial with a 1-year follow-up . SUBJECTS A total of 134 subjects with low back disorders . METHODS Participants with acute to chronic first or recurrent low back pain , excluding those with " red flag " criteria , were assigned r and omly to one of the 3 intervention groups : an orthopaedic manual therapy group ( n=45 ) , a McKenzie method group ( n=52 ) , and an " advice only to be active " group ( advice-only ) ( n=37 ) . Data on leg and low back pain intensity and disability ( Rol and -Morris Disability question naire ) were collected at baseline , and at 3- , 6- , and 12-month follow-up points . RESULTS At the 3-month follow-up point , significant improvements had occurred in all groups in leg and low back pain and in the disability index , but with no significant differences between the groups . At the 6-month follow-up , leg pain ( -15 mm ; 95 % confidence interval ( CI ) -30 to -1 ) , back pain ( effect : -15 mm ; -27 to -4 ) , and disability index ( -4 points ; -7 to -1 ) improved ( p < 0.05 ) more in the McKenzie method group than in the advice-only group . At the 1-year follow-up , the McKenzie method group had ( p=0.028 ) a better disability index ( -3 points ; -6 to 0 ) than did the advice-only group . In the orthopaedic manual therapy group at the 6-month and 1-year follow-up visits , improvements in the pain and disability index were somewhat better than in the advice-only group ( p=0.067 and 0.068 , respectively ) . No differences emerged between the orthopaedic manual therapy and McKenzie method groups in pain- and disability-score changes at any follow-up . CONCLUSION The orthopaedic manual therapy and McKenzie methods seemed to be only marginally more effective than was one session of assessment and advice-only & NA ; Since pain‐related fear may contribute to the development and maintenance of chronic low back pain ( CLBP ) , an exposure in vivo treatment ( EXP ) was developed for CLBP patients . We examined the effectiveness as well as specific mediating mechanisms of EXP versus operant grade d activity ( GA ) directly and 6 months post‐treatment in a multi‐centre r and omized controlled trial . In total , 85 patients suffering from disabling non‐specific CLBP reporting at least moderate pain‐related fear were r and omly allocated to EXP or GA . It was demonstrated that EXP , despite excelling in diminishing pain catastrophizing and perceived harmfulness of activities , was equally effective as GA in improving functional disability and main complaints , although the group difference almost reached statistical significance favouring EXP . Both treatment conditions did not differ in pain intensity and daily activity levels either . Nor was EXP superior to GA in the subgroup of highly fearful patients . Irrespective of treatment , approximately half the patients reported clinical ly relevant improvements in main complaints and functional disability , although for the latter outcome the group difference was almost significant favouring EXP . Furthermore , the effect of EXP relative to GA on functional disability and main complaints was mediated by decreases in catastrophizing and perceived harmfulness of activities . In sum , this study demonstrates that up to 6 months after treatment EXP is an effective treatment , but not more effective than GA , in moderately to highly fearful CLBP patients , although its superiority in altering pain catastrophizing and perceived harmfulness of activities is clearly established . Possible explanations for these findings are discussed BACKGROUND Previous studies indicate that yoga may be an effective treatment for chronic or recurrent low back pain . OBJECTIVE To compare the effectiveness of yoga and usual care for chronic or recurrent low back pain . DESIGN Parallel-group , r and omized , controlled trial using computer-generated r and omization conducted from April 2007 to March 2010 . Outcomes were assessed by postal question naire . ( International St and ard R and omised Controlled Trial Number Register : IS RCT N 81079604 ) SETTING 13 non-National Health Service premises in the United Kingdom . PATIENTS 313 adults with chronic or recurrent low back pain . INTERVENTION Yoga ( n = 156 ) or usual care ( n = 157 ) . All participants received a back pain education booklet . The intervention group was offered a 12-class , gradually progressing yoga program delivered by 12 teachers over 3 months . MEASUREMENTS Scores on the Rol and -Morris Disability Question naire ( RMDQ ) at 3 ( primary outcome ) , 6 , and 12 ( secondary outcomes ) months ; pain , pain self-efficacy , and general health measures at 3 , 6 , and 12 months ( secondary outcomes ) . RESULTS 93 ( 60 % ) patients offered yoga attended at least 3 of the first 6 sessions and at least 3 other sessions . The yoga group had better back function at 3 , 6 , and 12 months than the usual care group . The adjusted mean RMDQ score was 2.17 points ( 95 % CI , 1.03 to 3.31 points ) lower in the yoga group at 3 months , 1.48 points ( CI , 0.33 to 2.62 points ) lower at 6 months , and 1.57 points ( CI , 0.42 to 2.71 points ) lower at 12 months . The yoga and usual care groups had similar back pain and general health scores at 3 , 6 , and 12 months , and the yoga group had higher pain self-efficacy scores at 3 and 6 months but not at 12 months . Two of the 157 usual care participants and 12 of the 156 yoga participants reported adverse events , mostly increased pain . LIMITATION There were missing data for the primary outcome ( yoga group , n = 21 ; usual care group , n = 18 ) and differential missing data ( more in the yoga group ) for secondary outcomes . CONCLUSION Offering a 12-week yoga program to adults with chronic or recurrent low back pain led to greater improvements in back function than did usual care . PRIMARY FUNDING SOURCE Arthritis Research UK OBJECTIVE To investigate the outcome of a brief vocational-oriented intervention aim ing to motivate disability pensioners with back pain to return to work , and to evaluate prognostic factors for having entered a return to work process during the following year . DESIGN A r and omized controlled trial was conducted . SUBJECTS Participants ( n = 89 ) ( mean age 49 years , 65 % women ) who had received disability pension for more than one year were r and omized into an intervention group ( education , reassurance , motivation , vocational counselling , n = 45 ) and a control group ( n = 44 ) . METHODS Primary outcome measures were return to work or having entered a return to work process . Secondary outcome measures were life satisfaction , disability , fear avoidance behaviour and expectancy . RESULTS The intervention had no statistically significant effect on return to work or having entered a return to work process at 1-year follow-up . Twice as many in the intervention group ( n = 10 , 22 % ) had entered a return to work process compared with the controls ( n = 5 , 11 % ) . The number needed to treat was 9.2 ( 95 % confidence interval ( CI ) = 3.4 , Inf ) . Only minor differences in secondary outcome measures were demonstrated . Positive expectancy , better physical performance and less pain were related to return to work . CONCLUSION The effort of returning disability pensioners to work by a brief vocational-oriented intervention may be of clinical relevance . The effect needs to be explored further in larger sample s of disability pensioners OBJECTIVE The goal of this study was to compare the effects of trigger point ( TRP ) mesotherapy and acupuncture ( ACP ) mesotherapy in the treatment of patients with chronic low back pain . DESIGN Short term r and omized controlled trial . SETTING 62 subjects with chronic low back pain were recruited at out patients Physical Medicine and Rehabilitation Clinic at the University of Rome " La Sapienza " in the period between July 2006 and May 2008 . INTERVENTION Study subjects were assigned to receive 4 weeks treatments with either trigger point mesotherapy ( TRP mesotherapy , n=29 ) or acupoints mesotherapy ( ACP mesotherapy , n=33 ) . MAIN OUTCOME MEASURES Pain intensity with a pain visual analogic scale ( VAS ) and verbal rating scale ( VRS ) and pain disability with McGill Pain Question naire Short Form ( SFMPQ ) , Rol and Morris Disability Question naire ( RMQ ) and Oswestry Low Back Pain Disability Question aire ( ODQ ) . RESULTS ACP mesotherapy shows a more effective results in VRS and VAS measures in the follow-up ( p(VRS)=<.001 and p(VAS)=<.001 ) . The SF-MPQ measure shows a better results for ACP instead of TRP with statistically significant differences between groups and time ( p=.035 ) . Participants reported a slight discomfort at the time of the inoculation , and 15 % reported slight neck pain in ACP mesotherapy group . CONCLUSIONS Our results suggest that the response to ACP mesotherapy may be greater than the response to TRP mesotherapy in the short term follow-up . This technique could be nevertheless a viable option as an adjunct treatment in an overall treatment planning of CLBP Pain is a syndrome characterized by several neurophysiological changes including that of the autonomic nervous system . Chronic low back pain ( LBP ) is a major health problem and is a frequent reason for using unconventional therapies especially acupuncture . This study was conducted to evaluate the autonomic status and pain profile in chronic LBP patients and to observe the effect of electro acupuncture therapy . Chronic LBP patients ( n=60 ) were recruited from the Department of Orthopaedics , GTB Hospital , Delhi . Age and sex matched healthy volunteers were selected as controls ( n=30 ) . Following a written consent , LBP patients were r and omly allocated into two study groups - Group A received 10 sittings of electro acupuncture , on alternate days , at GB and UB points selected for back pain , while the Group B received a conventional drug therapy in the form of oral Valdecoxib together with supervised physiotherapy . Controls were assessed once while the patients were assessed twice , before and after completion of the treatment program ( 3 weeks ) . The autonomic status was studied with non-invasive cardiovascular autonomic function tests which included E : I ratio , 30:15 ratio , postural challenge test and sustained h and grip test . Pain intensity was measured with the visual analogue scale ( VAS ) and the global perceived effect ( GPE ) . Statistical analysis was performed using repeated measure 's ANOVA with Tukey 's test . Pain patients showed a significantly reduced vagal tone and increased sympathetic activity as compared to the controls ( P<0.05 to P<0.001 in different variables ) . Following treatment , both the study groups showed a reduction in vagal tone together with a decrease in the sympathetic activity . There was also a considerable relief of pain in both groups , however , the acupuncture group showed a better response ( P<0.01 ) . We conclude that there is autonomic dysfunction in chronic LBP patients . Acupuncture effectively relieves the pain and improves the autonomic status and hence can be used as an alternative/additive treatment modality in these cases Study Design . Preplanned secondary analysis of data from participants receiving acupuncture in a r and omized clinical trial . Objective . To determine whether patients ' expectations of and preferences for acupuncture predict short and long-term treatment outcomes for persons with chronic back pain . Summary of Background Data . Although accumulating evidence suggests that patient expectations and treatment preferences may predict treatment outcomes , few studies have examined this relationship for acupuncture . Methods . Four hundred seventy-seven acupuncture-naïve participants with chronic low back pain who were r and omized to 1 of 3 acupuncture or simulated acupuncture treatments were the focus of this analysis . Ten treatments were provided during a 7-week period , and participants were masked to treatment assignment . Before r and omization , participants provided expectations regarding treatment success , impressions , and knowledge about acupuncture and treatment preferences . Outcomes of interest were functional status ( Rol and score ) and symptom bothersomeness at 8 and 52 weeks postr and omization , obtained by telephone interviewers masked to treatment assignment . Results . Persons with high pretreatment expectations for the success of acupuncture were more likely to report greater general expectations for improvement , a preference for acupuncture , having heard acupuncture was a very effective treatment and having a very or moderately positive impression of acupuncture . However , none of these variables was a significant predictor of improvement in back-related symptoms or function at 8 or 52 weeks . After 1 treatment , participants ' revised expectations of treatment success were only associated with back-symptoms at the end of treatment . After 5 treatments , revised expectation of success was predictive of both symptoms and function at 8 and 52 weeks . Conclusion . Pretreatment expectations and preferences for acupuncture were not found predictive of treatment outcomes for patients with chronic back pain . These results differ from previous studies evaluating acupuncture for chronic back pain . These inconsistent results suggest that the relationship between expectations and outcomes may be more complex than previously believed Study Design . R and omized clinical trial . Objective . The purpose of this r and omized clinical trial was to examine the generalizability of 3 different manual therapy techniques in a patient population with low back pain that satisfy a clinical prediction rule ( CPR ) . Summary of Background Data . Recently a CPR that identifies patients with LBP who are likely to respond rapidly and dramatically to thrust manipulation has been developed and vali date d. The generalizability of the CPR requires further investigation . Methods . A total of 112 patients were enrolled in the trial and provided demographic information and completed a number of self-report question naires including the Oswestry Disability Question naire ( ODQ ) and the Numerical Pain Rating Scale ( NPRS ) at baseline , 1-week , 4-weeks , and 6-months . Patients were r and omly assigned to receive 1 of the 3 manual therapy techniques for 2 consecutive treatment sessions followed by exercise regimen for an additional 3 sessions . We examined the primary aim using a linear mixed model for repeated measures , using the ODQ and NPRS as dependent variables . The hypothesis of interest was the group by time interaction , which was further explored with pair-wise comparisons of the estimated marginal means . Results . There was a significant group x time interaction for the ODQ ( P < 0.001 ) and NPRS scores ( P = 0.001 ) . Pair-wise comparisons revealed no differences between the supine thrust manipulation and side-lying thrust manipulation at any follow-up period . Significant differences in the ODQ and NPRS existed at each follow-up between the thrust manipulation and the nonthrust manipulation groups at 1-week and 4-weeks . There was also a significant difference in ODQ scores at 6-months in favor of the thrust groups . Conclusion . The results of the study support the generalizability of the CPR to another thrust manipulation technique , but not to the nonthrust manipulation technique that was used in this study . In general , our results also provided support that the CPR can be generalized to different setting s from which it was derived and vali date d. However , additional research is needed to examine this issue The purpose of this study was to investigate the immediate effects of traditional Thai massage ( TTM ) on stress-related parameters including heart rate variability ( HRV ) , anxiety , muscle tension , pain intensity , pressure pain threshold , and body flexibility in patients with back pain associated with myofascial trigger points . Thirty-six patients were r and omly allocated to receive a 30-min session of either TTM or control ( rest on bed ) for one session . Results indicated that TTM was associated with significant increases in HRV ( increased total power frequency ( TPF ) and high frequency ( HF ) ) , pressure pain threshold ( PPT ) and body flexibility ( p<0.05 ) and significant decreases in self-reported pain intensity , anxiety and muscle tension ( p<0.001 ) . For all outcomes , similar changes were not observed in the control group . The adjusted post-test mean values for TPF , HF , PPT and body flexibility were significantly higher in the TTM group when compared with the control group ( p<0.01 ) and the values for pain intensity , anxiety and muscle tension were significantly lower . We conclude that TTM can increase HRV and improve stress-related parameters in this patient population Study Design . A prospect i ve single blinded placebo controlled study was conducted . Objective . To assess the effectiveness of spinal manipulation therapy ( SMT ) for the management of chronic nonspecific low back pain ( LBP ) and to determine the effectiveness of maintenance SMT in long-term reduction of pain and disability levels associated with chronic low back conditions after an initial phase of treatments . Summary of Background Data . SMT is a common treatment option for LBP . Numerous clinical trials have attempted to evaluate its effectiveness for different subgroups of acute and chronic LBP but the efficacy of maintenance SMT in chronic nonspecific LBP has not been studied . Methods . Sixty patients , with chronic , nonspecific LBP lasting at least 6 months , were r and omized to receive either ( 1 ) 12 treatments of sham SMT over a 1-month period , ( 2 ) 12 treatments , consisting of SMT over a 1-month period , but no treatments for the subsequent 9 months , or ( 3 ) 12 treatments over a 1-month period , along with “ maintenance spinal manipulation ” every 2 weeks for the following 9 months . To determine any difference among therapies , we measured pain and disability scores , generic health status , and back-specific patient satisfaction at baseline and at 1- , 4- , 7- , and 10-month intervals . Results . Patients in second and third groups experienced significantly lower pain and disability scores than first group at the end of 1-month period ( P = 0.0027 and 0.0029 , respectively ) . However , only the third group that was given spinal manipulations ( SM ) during the follow-up period showed more improvement in pain and disability scores at the 10-month evaluation . In the nonmaintained SMT group , however , the mean pain and disability scores returned back near to their pretreatment level . Conclusion . SMT is effective for the treatment of chronic nonspecific LBP . To obtain long-term benefit , this study suggests maintenance SM after the initial intensive manipulative therapy INTRODUCTION In recent decades the treatment of non-specific low back pain has turned to active modalities , some of which were based on cognitive-behavioural principles . Non-r and omised studies clearly favour functional multidisciplinary rehabilitation over outpatient physiotherapy . However , systematic review s and meta- analysis provide contradictory evidence regarding the effects on return to work and functional status . The aim of the present r and omised study was to compare long-term functional and work status after 3-week functional multidisciplinary rehabilitation or 18 supervised outpatient physiotherapy sessions . METHODS 109 patients with non-specific low back pain were r and omised to either a 3-week functional multidisciplinary rehabilitation programme , including physical and ergonomic training , psychological pain management , back school and information , or 18 sessions of active outpatient physiotherapy over 9 weeks . Primary outcomes were functional disability ( Oswestry ) and work status . Secondary outcomes were lifting capacity ( Spinal Function Sort and PILE test ) , lumbar range-of-motion ( modified-modified Schöber and fingertip-to-floor tests ) , trunk muscle endurance ( Shirado and Biering-Sörensen tests ) and aerobic capacity ( modified Bruce test ) . RESULTS Oswestry disability index was improved to a significantly greater extent after functional multidisciplinary rehabilitation compared to outpatient physiotherapy at follow-up of 9 weeks ( P = 0.012 ) , 9 months ( P = 0.023 ) and 12 months ( P = 0.011 ) . Work status was significantly improved after functional multidisciplinary rehabilitation only ( P = 0.012 ) , result ing in a significant difference compared to outpatient physiotherapy at 12 months ' follow-up ( P = 0.012 ) . Secondary outcome results were more contrasted . CONCLUSIONS Functional multidisciplinary rehabilitation was better than outpatient physiotherapy in improving functional and work status . From an economic point of view , these results should be backed up by a cost-effectiveness study OBJECTIVES Some occupations are more prone to low back pain ( LBP ) due to their static work postures and work place design . Multidisciplinary pain programs have shown their effectiveness in the management of LBP in general population but which treatment and which segment of the population will be benefited more was not investigated yet . This study determines the effect of two treatment protocol s on five occupationally subgrouped male LBP patients . METHODS A total of 102 occupational male , 20 - 40 yrs of age , with sub-acute or chronic nonspecific LBP were r and omized and treated either with conventional treatment a combination of two electrotherapy ( ultrasound and short wave diathermy ) and one exercise therapy ( lumbar strengthening exercises ) or dynamic muscular stabilization techniques ( DMST ) an active approach of stabilizing training . At the end of the treatment , subjects of both the groups were further stratified in five subgroups on the basis of their occupation . The pain was the primary outcome measure while physical strength [ back pressure changes ( BPC ) and abdominal pressure changes ( APC ) ] the secondary . RESULTS The Pain , BPC and APC of all subgroups improved significantly ( P < 0.01 ) in the both treatments but more in DMST . For each variable , improvement in subgroups differed within and between the treatments . Overall improvement in all assessed variables were evident on Desk workers followed by Shop keepers the most while BPC of Movement job , APC of Others and Pain of Sedentary and Shop keepers improved the least . CONCLUSIONS Study concluded that for the management of occupational LBP , DMST is more effective than conventional treatment . The Pain of Sedentary and Shopkeepers and physical strength of Movement job and Others may need more clinical attention . Findings of this study may be helpful in the management of occupational LBP Study Design . A r and omized prospect i ve cohort study of participants with chronic low back pain , seeking physical therapy , with follow-up at weeks 6 and 28 . Effects of conventional physiotherapy and physiotherapy with the addition of postural biofeedback were compared . Objective . To evaluate the benefits of postural biofeedback in chronic low back pain participants . Summary of Background Data . Biofeedback using electromyographic signals has been used in chronic low back pain with mixed results . Postural feedback had not been previously used . Methods . Demographic and psychological baseline data along with range of motion were analyzed from a sample of 47 chronic participants with low back pain r and omized into conventional physiotherapy with or without the addition of postural biofeedback . Results . After 6 months , there were 21 dropouts . The participants with biofeedback had markedly improved status in visual analog pain scales , short form-36 , and range of motion . Conclusion . The study strongly suggests that postural feedback is a useful adjunct to conventional physiotherapy of chronic low back pain participants Study Design . R and omized controlled trial . Objectives . To compare high- and low-intensity back schools with usual care in occupational health care . Summary of Background Data . The content and intensity of back schools vary widely and the method ologic quality of r and omized controlled trials is generally weak . Until now , no back school has proven to be superior for workers sick-listed because of subacute nonspecific low back pain . Methods . Workers ( n = 299 ) sick-listed for a period of 3 to 6 weeks because of nonspecific low back pain were recruited by the occupational physician and r and omly assigned to a high-intensity back school , a low-intensity back school , or care as usual . Outcome measures were days until return to work , total days of sick-leave , pain , functional status , kinesiophobia , and perceived recovery and were assessed at baseline and at 3 and 6 months of follow-up . Principal analyses were performed according to the intention-to-treat principle . Results . We r and omly allocated 299 workers . Workers in the low-intensity back school returned to work faster compared with usual care and the high-intensity back school , with hazard ratios of 1.4 ( P = 0.06 ) and 1.3 ( P = 0.09 ) , respectively . The comparison between high-intensity back school and usual care result ed in a hazard ratio of 1.0 ( P = 0.83 ) . The median number of sick-leave days was 68 , 75 , and 85 in the low-intensity back school , usual care , and high-intensity back school , respectively . Beneficial effects on functional status and kinesiophobia were found at 3 months in favor of the low-intensity back school . No substantial differences on pain and perceived recovery were found between groups . Conclusions . The low-intensity back school was most effective in reducing work absence , functional disability , and kinesiophobia , and more workers in this group scored a higher perceived recovery during the 6-month follow-up OBJECTIVES To determine the efficacy of wet-cupping for treating persistent nonspecific low back pain . BACKGROUND Wet-cupping therapy is one of the oldest known medical techniques . It is still used in several contemporary societies . Very minimal empirical study has been conducted on its efficacy . DESIGN R and omized controlled trial with two parallel groups . Patients in the experimental group were offered the option of referral to the wet-cupping service ; all accepted that option . The control group received usual care . SETTING Medical clinic in Kermanshah , Iran . PARTICIPANTS In total , 98 patients aged 17 - 68 years with nonspecific low back pain ; 48 were r and omly assigned to experimental group and 50 to the control group . INTERVENTION Patients in the experimental group were prescribed a series of three staged wet-cupping treatments , placed at 3 days intervals ( i.e. , 0 , 3 , and 6 days ) . Patients in the control group received usual care from their general practitioner . MAIN OUTCOME MEASURES Three outcomes assessed at baseline and again 3 months following intervention : the McGill Present Pain Index , Oswestry Pain Disability Index , and the Medication Quantification Scale . RESULTS Wet-cupping care was associated with clinical ly significant improvement at 3-month follow-up . The experimental group who received wet-cupping care had significantly lower levels of pain intensity ( [ 95 % confidence interval ( CI ) 1.72 - 2.60 ] mean difference=2.17 , p<0.01 ) , pain-related disability ( 95 % CI=11.18 - 18.82 , means difference=14.99 , p<0.01 ) , and medication use ( 95 % CI=3.60 - 9.50 , mean difference=6.55 , p<0.01 ) than the control group . The differences in all three measures were maintained after controlling for age , gender , and duration of lower back pain in regression models ( p<0.01 ) . CONCLUSIONS Traditional wet-cupping care delivered in a primary care setting was safe and acceptable to patients with nonspecific low back pain . Wet-cupping care was significantly more effective in reducing bodily pain than usual care at 3-month follow-up Objectives Publication bias may affect the validity of evidence based medical decisions . The aim of this study is to assess whether research outcomes affect the dissemination of clinical trial findings , in terms of rate , time to publication , and impact factor of journal publications . Methods and Findings All drug-evaluating clinical trials su bmi tted to and approved by a general hospital ethics committee between 1997 and 2004 were prospect ively followed to analyze their fate and publication . Published articles were identified by search ing Pubmed and other electronic data bases . Clinical study final reports su bmi tted to the ethics committee , final reports synopses available online and meeting abstract s were also considered as sources of study results . Study outcomes were classified as positive ( when statistical significance favoring experimental drug was achieved ) , negative ( when no statistical significance was achieved or it favored control drug ) and descriptive ( for non-controlled studies ) . Time to publication was defined as time from study closure to publication . A survival analysis was performed using a Cox regression model to analyze time to publication . Journal impact factors of identified publications were recorded . Publication rate was 48·4 % ( 380/785 ) . Study results were identified for 68·9 % of all completed clinical trials ( 541/785 ) . Publication rate was 84·9 % ( 180/212 ) for studies with results classified as positive and 68·9 % ( 128/186 ) for studies with results classified as negative ( p<0·001 ) . Median time to publication was 2·09 years ( IC95 1·61–2·56 ) for studies with results classified as positive and 3·21 years ( IC95 2·69–3·70 ) for studies with results classified as negative ( hazard ratio 1·99 ( IC95 1·55–2·55 ) . No differences were found in publication impact factor between positive ( median 6·308 , interquartile range : 3·141–28·409 ) and negative result studies ( median 8·266 , interquartile range : 4·135–17·157 ) . Conclusions Clinical trials with positive outcomes have significantly higher rates and shorter times to publication than those with negative results . However , no differences have been found in terms of impact factor Summary Acceptance and commitment therapy ( ACT ) and cognitive‐behavioral therapy are both effective for pain interference and mood in chronic pain patients ; ACT may be more satisfactory . ABSTRACT Individuals reporting chronic , nonmalignant pain for at least 6 months ( N = 114 ) were r and omly assigned to 8 weekly group sessions of acceptance and commitment therapy ( ACT ) or cognitive‐behavioral therapy ( CBT ) after a 4–6 week pretreatment period and were assessed after treatment and at 6‐month follow‐up . The protocol s were design ed for use in a primary care rather than specialty pain clinic setting . All participants remained stable on other pain and mood treatments over the course of the intervention . ACT participants improved on pain interference , depression , and pain‐related anxiety ; there were no significant differences in improvement between the treatment conditions on any outcome variables . Although there were no differences in attrition between the groups , ACT participants who completed treatment reported significantly higher levels of satisfaction than did CBT participants . These findings suggest that ACT is an effective and acceptable adjunct intervention for patients with chronic pain OBJECTIVE The aim of this study was to determine whether a 12-week course of low-frequency vibrating board therapy is a feasible therapy for non-specific chronic low back pain , and whether it improves the main outcome measures . DESIGN R and omized controlled trial . PATIENTS A total of 50 patients with non-specific low back pain were included . They were r and omly assigned to either a vibrating plate via reciprocation therapy group ( n = 25 ) or a control group ( n = 25 ) . METHODS The 12-week vibration therapy programme consisted of a total of 24 training sessions ( 2 times/week , with 1 day of rest between sessions ) . Assessment s of the main outcome measures for non-specific low back pain were performed at baseline and at 12 weeks . RESULTS In the vibration therapy group there was a statistically significant improvement , of 20.37 % ( p = 0.031 ) in the Postural Stability Index ( anterior-posterior ) ; 25.15 % ( p = 0.013 ) in the Oswestry Index ; 9.31 % in the Rol and Morris Index ( p = 0.001 ) ; 8.57 % ( p = 0.042 ) in EuroQol 5D-3L ; 20.29 % ( p = 0.002 ) in the Sens test ; 24.13 % ( p = 0.006 ) in visual analogue scale back ; and 16.58 % ( p = 0.008 ) in the Progressive Isoinertial Lifting Evaluation test . CONCLUSION A 12-week course of low-frequency vibrating board therapy is feasible and may represent a novel physical therapy for patients with non-specific low back pain Study Design . A review of the surgical costs and results in a group of patients r and omly allocated to surgery as part of a large prospect i ve r and omized trial of patients with chronic back pain . Objective . To report the observational data from the surgical arm of a r and omized trial comparing surgery with intensive rehabilitation for chronic low back pain . Clinical and economic data are reported . Summary of Background Data . Surgery for chronic low back pain is a well established but unproven intervention . The most cost-effective technique for spinal stabilization is still not established . Methods . One hundred six patients with chronic low back pain were r and omized to the surgical group of a r and omized trial comparing spinal fusion of the lumbar with a 3 week intensive rehabilitation program . The primary outcomes were the Oswestry Disability Index ( ODI ) and the Shuttle Walking Test measured at baseline and 2 years postr and omization . Patients were stratified by preoperative diagnosis , smoking habit , and litigation . Complications were assessed and costs analyzed . Results . Of the 176 surgical patients , 56 underwent postero-lateral fusion , 57 underwent interbody fusion , and 24 underwent flexible stabilization of the spine . The mean ODI for all patients in the surgical arm of the trial improved from a baseline of 46.5 ( SD 14.6 ) to 34.2 ( SD 21 ) at 2 years . Health care costs were higher ( £ 3109 difference ) for more complex procedures , and nearly 6 times as many early complications occurred with the more complex procedures . Smoking and unemployment were associated with worse results whereas litigation did not adversely affect the outcome . Conclusion . These observational changes in the ODI after surgery are similar to those reported from other studies of spinal fusion . More complex surgery is more expensive with more complications than postero-lateral fusion OBJECTIVE To investigate the effectiveness of a TTM-based motivational counselling approach by trained practice nurses to promote physical activity of low back pain patients in a German primary care setting . METHODS Data were collected in a cluster-r and omized controlled trial with three study arms via question naires and patient interviews at baseline and after 6 and 12 months . We analysed total physical activity and self-efficacy by using r and om effect models to allow for clustering . RESULTS A total of 1378 low back pain patients , many with acute symptoms , were included in the study . Nearly 40 % of all patients reported sufficient physical activity at baseline . While there were significant improvements in patients ' physical activity behaviour in all study arms , there was no evidence for an intervention effect . CONCLUSION The outcome may be explained by insufficient performance of the practice nurses , implementation barriers caused by the German health care system and the heterogenous sample . PRACTICE IMPLICATION S Given the objective to incorporate practice nurses into patient education , there is a need for a better basic training of the nurses and for a change towards an organizational structure that facilitates patient-nurse communication . Counselling for low back pain patients has to consider more specificated aims for different subgroups Background Chronic non-specific low back pain ( LBP ) is a prevalent ( 80 % ) and multi-dimensional illness . This study aims to test whether acupuncture , baclofen , or combined treatment with acupuncture and baclofen alleviates symptoms of non-specific chronic LBP in men . Methods Eight-four ( 84 ) men aged 50 - 60 years with non-specific chronic LBP were r and omly assigned to four groups : the baclofen group received only baclofen ( 30 mg/day ) ; the acupuncture group received only acupuncture at selected acupoints ; the acupuncture + baclofen group received combined treatment with acupuncture and baclofen treatments ; and the control group received no pain reduction treatment . After five weeks of treatment , visual analogue scale ( VAS ) and self-reported pain disability with the Rol and -Morris Disability Question naire ( RDQ ) were conducted for outcome measures . Results After treatment , the baclofen , acupuncture and acupuncture + baclofen groups all had lower VAS and RDQ scores . Significantly higher reduction and improvement in VAS and RDQ scores were found in the acupuncture and acupuncture + baclofen groups compared to the baclofen group . Conclusion The present study indicates that the combined treatment of acupuncture and baclofen is more effective than baclofen treatment alone to reduce pain in patients with non-specific chronic LBP.Trial registration Background : Eel calcitonin ( elcatonin ) injection is widely used for elderly patients suffering from somatic pain in Japan . However , there have been few reports on the analgesic effects of elcatonin injection . The purpose of this study was to examine the analgesic effects of elcatonin injection in postmenopausal women with lower back pain . Methods : This study was design ed as a double-blind , r and omized , placebo-controlled study . Thirty-six women aged ≥50 years with acute lower back pain participated in this study . They were r and omly divided into two treatment groups according to whether they received a placebo or a weekly trigger point injection of elcatonin ( 20 units ) . They were observed for 5 weeks and the extent of pain at motion and at rest according to the visual analog scale ( VAS ) was evaluated . The mean VAS scores for the elcatonin group were then compared with those of the placebo group . Results : There were no statistically significant differences in the mean VAS scores for pain at rest between the two groups during the 5-week treatment course . However , the mean VAS scores for motion pain in the elcatonin group were significantly lower than those in the placebo group at the third , fifth and sixth weeks . Conclusions : Elcatonin injection ( 20 units ) significantly relieved motion pain in the lower back in postmenopausal women after three weeks of treatment . This analgesic effect continued for the subsequent 3 weeks Background The causes of chronic low back pain ( CLBP ) remain obscure and effective treatment of symptoms remains elusive . A mechanism of relieving chronic pain based on the consequences of conflicting unpleasant sensory inputs to the central nervous system has been hypothesised . As a result a device was generated to deliver sensory discrimination training ( FairMed ) , and this r and omised controlled trial compared therapeutic effects with a comparable treatment modality , TENS . Methods 60 patients with CLBP were recruited from physiotherapy referrals to a single-blinded , r and omised controlled , non-inferiority trial . They were r and omised to receive either FairMed or TENS and asked to use the allocated device for 30 minutes , twice a day , for 3 weeks . The primary outcome variable measured at 0 and 3 weeks was pain intensity measured using a visual analogue scale averaged over 7 days . Secondary outcome measures were Oswestry Disability Index , 3 timed physical tests , 4 question naires assessing different aspects of emotional coping and a global measure of patient rating of change . Data were analysed for the difference in change of scores between groups using one-way ANOVA . Results Baseline characteristics of the two groups were comparable . The primary outcome , change in pain intensity ( VAS ) at 3 weeks showed a mean difference between groups of -0.1 , ( non significant p = 0.82 ) . The mean difference in change in ODI scores was 0.4 ; ( non significant p = 0.85 ) . Differences in change of physical functioning showed that no significant difference in change of scores for any of these test ( p = 0.58 – 0.90 ) . Changes in scores of aspects of emotional coping also demonstrated no significant difference in change scores between the groups ( p = 0.14 – 0.94 ) . Conclusion FairMed was not inferior to TENS treatment . The findings have implication s for further research on current chronic pain theories and treatments . Further work to explore these mechanisms is important to exp and our underst and ing of chronic pain and the role of neuro-modulation . Trial Registration UKCRN Study ID Background In the treatment of chronic back pain , cognitive methods are attracting increased attention due to evidence of effectiveness similar to that of traditional therapies . The purpose of this study was to compare the effectiveness of performing a cognitive intervention based on a non-injury model with that of a symptom-based physical training method on the outcomes of low back pain ( LBP ) , activity limitation , LBP attitudes ( fear-avoidance beliefs and back beliefs ) , physical activity levels , sick leave , and quality of life , in chronic LBP patients . Methods The study was a pragmatic , single-blind , r and omised , parallel-group trial . Patients with chronic/recurrent LBP were r and omised to one of the following treatments : 1 . Educational programme : the emphasis was on creating confidence that the back is strong , that loads normally do not cause any damage despite occasional temporary pain , that reducing the focus on the pain might facilitate more natural and less painful movements , and that it is beneficial to stay physically active . 2 . Individual symptom-based physical training programme : directional-preference exercises for those central ising their pain with repetitive movements ; ' stabilising exercises ' for those deemed ' unstable ' based on specific tests ; or intensive dynamic exercises for the remaining patients . Follow-up question naires ( examiner-blinded ) were completed at 2 , 6 and 12 months . The main statistical test was an ANCOVA adjusted for baseline values . Results A total of 207 patients participated with the median age of 39 years ( IQR 33 - 47 ) ; 52 % were female , 105 were r and omised to the educational programme and 102 to the physical training programme . The two groups were comparable at baseline . For the primary outcome measures , there was a non-significant trend towards activity limitation being reduced mostly in the educational programme group , although of doubtful clinical relevance . Regarding secondary outcomes , improvement in fear-avoidance beliefs was also better in the educational programme group . All other variables were about equally influenced by the two treatments . The median number of treatment sessions was 3 for the educational programme group and 6 for the physical training programme group . Conclusions An educational approach to treatment for chronic LBP result ed in at least as good outcomes as a symptom-based physical training method , despite fewer treatment sessions . Trial registration Clinical trials.gov : # Study Design . This study was a prospect i ve , r and omized , controlled study . Objective . To compare the effectiveness of aquatic exercise interventions with l and -based exercises in the treatment of chronic low back pain ( CLBP ) . Summary of Background Data . L and -based exercise and physiotherapy are the main treatment tools used for CLBP . Clinical experience indicates that aquatic exercise may have advantages for patients with musculoskeletal disorders . Methods . A total of 65 patients with CLBP were included in this study . Patients were r and omly assigned to receive aquatic exercise or l and -based exercise treatment protocol . Aquatic exercise program consisted of 20 sessions , 5 × per week for 4 weeks in a swimming pool at 33 ° C . L and -based exercise ( home-based exercise ) program were demonstrated by a physiotherapist on one occasion and then they were given written advice The patients were assessed for spinal mobility , pain , disability , and quality of life . Evaluations were performed before treatment ( week 0 ) and after treatment ( week 4 and week 12 ) . Results . In both groups , statistically significant improvements were detected in all outcome measures ( except modified Schober test ) compared with baseline . However , improvement in modified Oswestry Low Back Pain Disability question naire and physical function and role limitations due to physical functioning subpart of Short-Form 36 Health Survey were better in aquatic exercise group ( P < 0.05 ) . Conclusion . It is concluded that a water-based exercises produced better improvement in disability and quality of life of the patients with CLBP than l and -based exercise BACKGROUND Acupuncture is a popular complementary and alternative treatment for chronic back pain . Recent European trials suggest similar short-term benefits from real and sham acupuncture needling . This trial addresses the importance of needle placement and skin penetration in eliciting acupuncture effects for patients with chronic low back pain . METHODS A total of 638 adults with chronic mechanical low back pain were r and omized to individualized acupuncture , st and ardized acupuncture , simulated acupuncture , or usual care . Ten treatments were provided over 7 weeks by experienced acupuncturists . The primary outcomes were back-related dysfunction ( Rol and -Morris Disability Question naire score ; range , 0 - 23 ) and symptom bothersomeness ( 0 - 10 scale ) . Outcomes were assessed at baseline and after 8 , 26 , and 52 weeks . RESULTS At 8 weeks , mean dysfunction scores for the individualized , st and ardized , and simulated acupuncture groups improved by 4.4 , 4.5 , and 4.4 points , respectively , compared with 2.1 points for those receiving usual care ( P < .001 ) . Participants receiving real or simulated acupuncture were more likely than those receiving usual care to experience clinical ly meaningful improvements on the dysfunction scale ( 60 % vs 39 % ; P < .001 ) . Symptoms improved by 1.6 to 1.9 points in the treatment groups compared with 0.7 points in the usual care group ( P < .001 ) . After 1 year , participants in the treatment groups were more likely than those receiving usual care to experience clinical ly meaningful improvements in dysfunction ( 59 % to 65 % vs 50 % , respectively ; P = .02 ) but not in symptoms ( P > .05 ) . CONCLUSIONS Although acupuncture was found effective for chronic low back pain , tailoring needling sites to each patient and penetration of the skin appear to be unimportant in eliciting therapeutic benefits . These findings raise questions about acupuncture 's purported mechanisms of action . It remains unclear whether acupuncture or our simulated method of acupuncture provide physiologically important stimulation or represent placebo or nonspecific effects Objective To compare the effectiveness of repeated acupuncture stimulation and local anaesthetic injection at the most painful points in patients with low back pain . Method This r and omised controlled clinical trial involved 26 patients with low back pain r and omly allocated to either an acupuncture group ( n = 13 ) or a local anaesthetic injection group ( n = 13 ) . Both acupuncture and anaesthetic injection were performed at two to five of the most painful points on the lower back once weekly for 4 weeks . In the acupuncture group , a 0.18 mm diameter stainless steel needle was inserted to a depth of 10–20 mm and manual stimulation was applied . In the local anaesthetic injection group , a 0.5 mm diameter needle was inserted to a depth of 10–20 mm and a local anaesthetic was injected . Participants evaluated pain using a Visual Analogue Scale immediately before and after the first treatment , before each subsequent treatment , and at 2 weeks and 4 weeks after completion of treatment . Results There was a significant difference between the two groups in the change in Visual Analogue Scale pain scores ( p<0.01 ) , with acupuncture providing more favourable results than local anaesthetic injection . The reduction in pain score from baseline calculated at each time period was significantly different between the two groups after the first ( p<0.05 ) and final ( p<0.01 ) treatments , and during the follow-up period ( after 2 weeks ( p<0.01 ) and 4 weeks ( p<0.05 ) ) . Conclusion Both injection and acupuncture relieved pain , but acupuncture was superior for the immediate and sustained effects , suggesting that it is a useful treatment for low back pain . The difference in the effects may be attributable to differences in the mechanism of pain suppression The objective of this study is to compare the costs and benefits of a grade d activity ( GA ) intervention to usual care ( UC ) for sick-listed workers with non-specific low back pain ( LBP ) . The study is a single-blind , r and omized controlled trial with 3-year follow-up . A total of 134 ( 126 men and 8 women ) predominantly blue-collar workers , sick-listed due to LBP were recruited and r and omly assigned to either GA ( N = 67 ; mean age 39 ± 9 years ) or to UC ( N = 67 ; mean age 37 ± 8 years ) . The main outcome measures were the costs of health care utilization during the first follow-up year and the costs of productivity loss during the second and the third follow-up year . At the end of the first follow-up year an average investment for the GA intervention of € 475 per worker , only € 83 more than health care utilization costs in UC group , yielded an average savings of at least € 999 ( 95 % CI : −1,073 ; 3,115 ) due to a reduction in productivity loss . The potential cumulative savings were an average of € 1,661 ( 95 % CI : −4,154 ; 6,913 ) per worker over a 3-year follow-up period . It may be concluded that the GA intervention for non-specific LBP is a cost-beneficial return-to-work intervention Abstract Objective To evaluate the effectiveness of acupressure in terms of disability , pain scores , and functional status . Design R and omised controlled trial . Setting Orthopaedic clinic in Kaohsiung , Taiwan . Participants 129 patients with chronic low back pain . Intervention Acupressure or physical therapy for one month . Main outcome measures Self administered Chinese versions of st and ard outcome measures for low back pain ( primary outcome : Rol and and Morris disability question naire ) at baseline , after treatment , and at six month follow-up . Results The mean total Rol and and Morris disability question naire score after treatment was significantly lower in the acupressure group than in the physical therapy group regardless of the difference in absolute score ( - 3.8 , 95 % confidence interval - 5.7 to - 1.9 ) or mean change from the baseline ( - 4.64 , - 6.39 to - 2.89 ) . Acupressure conferred an 89 % ( 95 % confidence interval 61 % to 97 % ) reduction in significant disability compared with physical therapy . The improvement in disability score in the acupressure group compared with the physical group remained at six month follow-up . Statistically significant differences also occurred between the two groups for all six domains of the core outcome , pain visual scale , and modified Oswestry disability question naire after treatment and at six month follow-up . Conclusions Acupressure was effective in reducing low back pain in terms of disability , pain scores , and functional status . The benefit was sustained for six months Abstract Objective To determine whether a short course of traditional acupuncture improves longer term outcomes for patients with persistent non-specific low back pain in primary care . Design Pragmatic , open , r and omised controlled trial . Setting Three private acupuncture clinics and 18 general practice s in York , Engl and . Participants 241 adults aged 18 - 65 with non-specific low back pain of 4 - 52 weeks ' duration . Interventions 10 individualised acupuncture treatments from one of six qualified acupuncturists ( 160 patients ) or usual care only ( 81 patients ) . Main outcome measures The primary outcome was SF-36 bodily pain , measured at 12 and 24 months . Other outcomes included reported use of analgesics , scores on the Oswestry pain disability index , safety , and patient satisfaction . Results 39 general practitioners referred 289 patients of whom 241 were r and omised . At 12 months average SF-36 pain scores increased by 33.2 to 64.0 in the acupuncture group and by 27.9 to 58.3 in the control group . Adjusting for baseline score and for any clustering by acupuncturist , the estimated intervention effect was 5.6 points ( 95 % confidence interval −0.2 to 11.4 ) at 12 months ( n = 213 ) and 8.0 points ( 2.8 to 13.2 ) at 24 months ( n = 182 ) . The magnitude of the difference between the groups was about 10%-15 % of the final pain score in the control group . Functional disability was not improved . No serious or life threatening events were reported . Conclusions Weak evidence was found of an effect of acupuncture on persistent non-specific low back pain at 12 months , but stronger evidence of a small benefit at 24 months . Referral to a qualified traditional acupuncturist for a short course of treatment seems safe and acceptable to patients with low back pain . Trial registration IS RCT N80764175 [ controlled-trials.com ] QUESTION Is eight weeks of high-intensity strengthening of the isolated lumbar extensors more effective than low-intensity strengthening or no strengthening ? Are any gains maintained 16 weeks later ? DESIGN R and omised , three-arm trial with concealed allocation , assessor blinding , and intention-to-treat- analysis . Participants in the waiting list control group were r and omised again , after the first 8 weeks , to either the high-intensity or the low-intensity strengthening program . PARTICIPANTS Sixty-five army personnel with non-specific chronic low back pain . INTERVENTION The high-intensity training group received 10 sessions of 15 to 20 repetitions for the isolated lumbar extensor muscles . The low-intensity training group received a nonprogressive , low-intensity resistance protocol . OUTCOME MEASURES Primary outcomes were global perceived effect and disability . Secondary outcomes were health-related quality of life , fear of movement/(re-)injury , and isometric lumbar extensor muscle strength . Measures were taken before and after the training and 16 weeks later . RESULTS At eight weeks , SF-36 overall score was on average 7 % ( 95 % CI 1 to 13 ) greater in the high-intensity training group compared with the low-intensity training group and the waiting list control group , and self-assessed decrease of back symptoms was on average 39 % ( 95 % CI 14 to 64 ) greater in the high-intensity training group compared with the waiting list control group . There was no difference in improvement between the groups for any other outcome at 8 weeks or 24 weeks . CONCLUSIONS Although some beneficial effects were found , the results of this high-intensity strengthening program of the isolated lumbar extensor muscles do not clearly support the generally-cl aim ed beneficial influence of exercise for chronic non-specific low back pain Background The effectiveness of injection therapy for low-back pain is still debatable . We compared the efficacy of local injections of the homeopathic preparation Disci/Rhus toxicodendron compositum ( verum ) with placebo injections and with no treatment in patients with chronic low back pain . Methodology /Principal Findings In a r and omized controlled partly double blind multicenter trial patients with chronic low back pain from 9 German outpatient clinics were enrolled and r and omly allocated in a 1∶1∶1 ratio to receive subcutaneous injections ( verum or placebo ) into painful sites on the lower back over 12 treatment sessions within eight weeks , or no treatment ( rescue pain medication with paracetamol or NSAIDs ) . All trial personnel and participants were masked to treatment allocation . The primary outcome measure was the average pain intensity over the last seven days on a visual analogue scale ( 0–100 mm , 0 = no pain , 100 = worst imaginable pain ) after eight weeks . Follow-up was 26 weeks . Primary analysis was by intention to treat . Between August 2007 and June 2008 , 150 patients were r and omly allocated to three groups ( 51 verum , 48 placebo and 51 no treatment ) . The mean baseline-adjusted low back pain intensity at week eight was : verum group 37.0 mm ( 97.5 % CI 25.3;48.8 ) , no treatment group 53.0 ( 41.8;64.2 ) , and placebo group 41.8 ( 30.1;53.6 ) . The verum was significantly superior to no treatment ( P = 0.001 ) , but not to placebo ( P = 0.350 ) . No significant side effects were reported . Conclusions / Significance The homeopathic preparation was not superior to placebo . Compared to no treatment injections result ed in significant and clinical relevant chronic back pain relief . Trial Registration Clinical Trials.gov Background Exercise benefits patients with chronic nonspecific low back pain ; however , the most effective type of exercise remains unknown . Objective This study compared outcomes after motor control exercises , sling exercises , and general exercises for low back pain . Design This was a r and omized controlled trial with a 1-year follow-up . Setting The study was conducted in a primary care setting in Norway . Patients The participants were patients with chronic nonspecific low back pain ( n=109 ) . Interventions The interventions in this study were low-load motor control exercises , high-load sling exercises , or general exercises , all delivered by experienced physical therapists , once a week for 8 weeks . Measurements The primary outcome measure was pain reported on the Numeric Pain Rating Scale after treatment and at a 1-year follow-up . Secondary outcome measures were self-reported activity limitation ( assessed with the Oswestry Disability Index ) , clinical ly examined function ( assessed with the Fingertip-to-Floor Test ) , and fear-avoidance beliefs after intervention . Results The postintervention assessment showed no significant differences among groups with respect to pain ( overall group difference ) or any of the outcome measures . Mean ( 95 % confidence interval ) group differences for pain reduction after treatment and after 1 year were 0.3 ( −0.7 to 1.3 ) and 0.4 ( −0.7 to 1.4 ) for motor control exercises versus sling exercises , 0.7 ( −0.6 to 2.0 ) and 0.3 ( −0.8 to 1.4 ) for sling exercises versus general exercises , and 1.0 ( −0.1 to 2.0 ) and 0.7 ( −0.3 to 1.7 ) for motor control exercises versus general exercises . Limitations The nature of the interventions made blinding impossible . Conclusions This study gave no evidence that 8 treatments with individually instructed motor control exercises or sling exercises were superior to general exercises for chronic low back pain OBJECTIVE To evaluate the influence of pain on vertical ground-reaction force ( VGRF ) in patients with low back problems and the effect of the Pilates method on the gait of these patients . DESIGN A single-blind r and omized controlled trial . PARTICIPANTS 28 individuals assigned to a control group ( n = 11 ) and a low-back group ( n = 17 ) , the latter of which was subdivided into a Pilates group ( n = 8) and a no-Pilates group ( n = 9 ) . INTERVENTION The Pilates group undertook 15 sessions of Pilates . MAIN OUTCOME MEASURES The VGRF parameters were recorded during preferred and faster walking speeds . The data were collected before and after the intervention . RESULTS The weight-acceptance rate and push-off rate were significantly less in the right lower limb of low-back group than of the control group at preferred speed . Improvements were seen in the Pilates group postintervention , with increased middle-support force for the left lower limb at faster walking speed and decreased pain ; this did not occur in the no-Pilates group . CONCLUSIONS These results suggest that patients with low back pain use strategies to attenuate the amount of force imposed on their body . The Pilates method can improve weight discharge in gait and reduce pain compared with no intervention OBJECTIVE The objective of this study was to examine whether a multimodal , secondary prevention program ( MP ) is superior to a general physical exercise program ( EP ) in influencing the process leading to chronic low back pain ( LBP ) in nurses with a history of back pain . DESIGN The study was conducted as a r and omized controlled parallel-group trial . SETTING The interventions were performed in a single center at the Department of Physical and Rehabilitation Medicine at the University of Munich in Germany . PARTICIPANTS A total of 235 nurses from 14 nearby hospitals and nursing homes who experienced at least one episode of back pain during the previous 2 years were invited into the study . Of these , 183 nurses were enrolled and 169 ( 83 in the MP and 86 in the EP ) qualified for the intent-to-treat analysis . INTERVENTIONS The EP consisted of 11 group sessions , each lasting 1 hour . After introductory sessions , subsequent sessions included general physical strengthening and stretching exercises as well as instructions for a home-training program . The MP consisted of 17 group sessions of 1.75 hours and one individual session of 45 minutes . In addition to the full EP , the MP included 5 psychological units , 7 segmental stabilization exercises units , and 8 ergonomic and workplace-specific units . MAIN OUTCOME MEASUREMENTS The primary study end-point variable was pain interference , and the secondary study end-point variables were pain intensity and functioning as measured with the West Haven-Yale Multidimensional Pain Inventory and the Short Form-36 , respectively . These study end-point variables were defined a priori . RESULTS There was no statistically significant difference between the 2 groups . Small-to-moderate effects were observed in both intervention programs across all study end-point variables . For pain interference , the effect size at 12 months after intervention was 0.58 in the MP and 0.47 in the EP . CONCLUSIONS A multimodal program is not superior to a general exercise program in influencing the process leading to chronic LBP in a population of nurses with a history of pain . The most likely explanation is a common psychological mechanism leading to improved pain interference that is irrespective of the program used . Considering the lower re sources of the general exercise program , the expense for a multimodal program is not justified for the secondary prevention of LBP and disability High-velocity spinal manipulation is commonly adopted for treating chronic low-back pain ( CLBP ) and has been associated with changes in muscle activity , but the evidence is controversial . The aim of this study was to analyse the immediate effects of high-velocity spine manipulation on paraspinal activity during flexion-extension trunk movements . Forty nonspecific CLBP patients were r and omised into two groups , manipulation ( n = 20 ) and control ( n = 20 ) . While the manipulation group received high-velocity spine manipulation at the L4-L5 level , the control group remained lying in the same position . EMG-related variables , perceived pain intensity ( 100 mm VAS ) and finger-floor distance were collected before and after spinal manipulation at the L4-L5 level . EMG surface signals from the right and left paraspinal muscles ( L5-S1 level ) were acquired during trunk flexion-extension cycles . EMG activity during the static relaxation phase was significantly reduced following intervention for the manipulation group but not for the control group . The extension-phase EMG activity was also reduced after manipulation , but the flexion-phase EMG levels remained unchanged . Accordingly , the percent changes in FRR and ERR were significantly larger for the manipulation group compared to the control . The results suggest that a high-velocity spinal manipulation is able to acutely reduce abnormal EMG activity during the full-flexion static phase and activation during the extension phase Kell , RT , Risi , AD , and Barden , JM . The response of persons with chronic nonspecific low back pain to three different volumes of periodized musculoskeletal rehabilitation . J Strength Cond Res 25(4 ) : 1052 - 1064 , 2011-Chronic nonspecific low back pain ( CLBP ) is a common musculoskeletal health issue associated with pain and disability reduced quality of life ( QoL ) . Pain initiates a fear-avoidance cycle , which needs to be broken if rehabilitation is to work . To break this cycle , exercise must be gradual and focused on strengthening the weakened musculature . Recently , periodized resistance training was effectively used as a musculoskeletal rehabilitation for adults with CLBP . The purpose of this study was to determine if the volume of periodized musculoskeletal rehabilitation ( PMR ) influences strength , pain , disability , and QoL in untrained persons . Subjects ( n = 240 ) were age and sex matched , with attempts made to match on strength and pain , and r and omly assigned to groups after baseline testing : ( a ) 4 days per week ( 4D ; n = 60 ) , ( b ) 3 days per week ( 3D ; n = 60 ) ( c ) , 2 days per week ( 2D ; n = 60 ) training volume or control ( C ; n = 60 ) with no training . The PMR program progressively overloaded muscle groups , with mean training volumes of 4D ( 1,563 repetitions [ reps ] per week ) , 3D ( 1,344 reps per week ) , and 2D ( 564 reps per week ) . Three weeks of familiarization and 13 weeks of PMR were employed . The 4D training volume significantly ( p ≤ 0.05 ) outperformed all other training volumes by weeks 9 and 13 . However , all training volumes made significant ( p ≤ 0.05 ) improvements in strength , pain , disability , and QoL across time . The effect sizes ( ESs ) associated with the group means of the outcome measures ranged from moderate to strong , with the 4D training volume consistently demonstrating the largest ESs . The 4D training volume is most effective at treating CLBP . Periodization can not only be applied to athlete training but also to the rehabilitation setting This r and omized controlled clinical trial compares the effectiveness of a biopsychosocial treatment with a solely conventional biomedical therapy in patients with subacute low back pain using parameters for pain intensity , functional status , depressive dysfunction and work performance . Sixty-four patients with a first-time sick leave between 3 and 12 weeks due to low back pain were r and omly assigned to either a conventional biomedical therapy ( MT ; n=33 ) group , or a biopsychosocial therapy ( BT ; n=31 ) group including a psychotherapeutic module ; both in accordance with a st and ardized 3 weeks inpatient treatment . Pain intensity , functional back capacity , clinical parameters and depressive dysfunction revealed significant improvement in both treatment groups at end of 3 weeks therapy ( T1 ) . However , at 6 months ( T2 ) , analysis revealed significant better results for nearly all parameters in the BT group that showed further improvement from T1 to T2 , whereas the values in the MT group deteriorated from T1 back to the baseline values . During the 2-year period after therapy , 10 % in MT and 59 % in BT required no further sick leave due to low back pain . The results of the study indicate that a psychotherapeutic element in the treatment of low back pain appears to positively influence pain , functional status and work performance when conducted at an early stage of chronification and helps in the achievement of a better outcome ABSTRACT Background : Short-acting opioids are commonly used to treat breakthrough pain ( BTP ) and rapid-onset formulations are being developed to improve the effectiveness of this approach . Fentanyl buccal tablet ( FBT ) is a new formulation of fentanyl that enhances transbuccal drug delivery via an effervescent reaction and may provide relatively rapid-onset analgesia . FBT was evaluated for BTP in opioid-treated patients with chronic low back pain – the first such study in a population with chronic non-cancer pain . Design : R and omized , double-blind , placebo-controlled . Patients and setting : Patients with chronic low back pain receiving long-term opioid therapy at 16 pain treatment centers in the United States . Procedures : Following open-label titration to identify an effective FBT dose , patients were r and omly assigned to one of three double-blind dose sequences ( six doses of FBT , three placebo ) to treat nine BTP episodes . Pain intensity ( PI ) , measured on an 11-point scale ( 0 = no pain ; 10 = worst pain ) , and other outcomes were assessed for 2 h after dosing . Data analysis : The primary efficacy measure was the sum of pain intensity differences ( PIDs ) for the first 60 min ( SPID60 ) ; secondary efficacy measures included PIDs at other time points , pain relief ( PR ) , meaningful PR , time to meaningful PR , use of supplementary BTP medication , and self/investigator-reported adverse events . Results : Of the 124 patients screened , 105 patients were enrolled , 84 identified an effective FBT dose , and 77 entered the double-blind phase . SPID60 significantly favored FBT ( p < 0.0001 ) . All secondary measures also favored FBT , with PIDs and PR showing significant differences versus placebo as early as 10 and 15 min , respectively . An improvement in PI score of ≥ 33 % occurred in a significantly larger proportion of FBT-treated episodes versus placebo from 15 min ( 20 % vs. 11 % , p < 0.01 ) through 2 h ( 65 % vs. 28 % , p < 0.0001 ) . Patients were approximately four times more likely to require supplemental opioids for BTP episodes following administration of placebo compared with episodes treated with FBT . AEs were typical for opioids , and were mostly reported during dose titration . Limitations of this study may be related to its open-label dose-titration phase ( which has the potential to compromise blinding ) and the recruitment of patients from pain clinics , which could potentially yield a study population that is not representative of the general population with BTP . Conclusions : FBT was efficacious and well tolerated in the treatment of BTP in opioid-treated patients with chronic low back pain Study Design . A r and omized controlled trial . Objectives . To determine 1 ) whether , among patients with persistent disabling low back pain ( LBP ) , a group program of exercise and education using a cognitive behavioral therapy ( CBT ) approach , reduces pain and disability over a subsequent 12-month period ; 2 ) the cost-effectiveness of the intervention ; and 3 ) whether a priori preference for type of treatment influences outcome . Summary of Background Data . There is evidence that both exercise and CBT delivered in specialist setting s is effective in improving LBP . There is a lack of evidence on whether such interventions , delivered by trained individuals in primary care , result in improved outcomes . Methods . The study was conducted in nine family medical practice s in East Cheshire , UK . Patients 18 to 65 years of age , consulting with LBP , were recruited ; those still reporting LBP 3 months after the initial consultation were r and omized between the two trial arms . The intervention arm received a program of eight 2-hour group exercise session over 6 weeks comprising active exercise and education delivered by physiotherapists using a CBT approach . Both arms received an educational booklet and audio-cassette . The primary outcome measures were pain ( 0–100 Visual Analogue Scale ) and disability ( Rol and and Morris Disability Scale ; score 0–24 ) . Results . A total of 196 subjects ( 84 % ) completed follow-up 12 months after the completion of the intervention program . The intervention showed only a small and nonsignificant effect at reducing pain ( −3.6 mm ; 95 % confidence interval , −8.5 , 1.2 mm ) and disability ( −0.6 score ; 95 % confidence interval , −1.6 , 0.4 ) . The cost of the intervention was low with an incremental cost-effectiveness ratio of £ 5000 ( U.S. $ 8650 ) per quality adjusted life year . In addition , patients allocated to the intervention that had expressed a preference for it had clinical ly important reductions in pain and disability . Conclusions . This intervention program produces only modest effects in reducing LBP and disability over a 1-year period . The observation that patient preference for treatment influences outcome warrants further investigation BACKGROUND Kinesio Taping ( KT ) has proved to be effective in various musculoskeletal conditions . Although its precise working mechanism has yet to be fully understood , it is believed to interact with neuromuscular function through mechanoceptor activation . No studies design ed to assess the effects of KT in chronic low back pain ( CLBP ) patients have yet been conducted . AIM The aim of this study was to determine the effects of KT on pain , disability and lumbar muscle function in sufferers of CLBP , both immediately and at a one-month follow-up examination . DESIGN The study consisted of two phases : phase I was based on an intra-subject pre-test/post-test procedure ; phase II was based on a r and omized , single-blinded controlled trial . SETTING Outpatient facility . POPULATION Thirty-nine CLBP patients were enrolled . METHODS KT plus exercise , KT alone or exercise alone have been used for four weeks . Pain , disability and lumbar muscle function were evaluated before and after the treatment period . RESULTS The patients in all three groups displayed a significant reduction in pain after treatment , though only the exercise-alone group displayed reduced disability . A return to normal lumbar muscle function was observed in 28 % of patients , but was not related to a reduction in pain . CONCLUSION When applied to CLBP patients , KT leads to pain relief and lumbar muscle function normalization shortly after its application ; these effects persist over a short follow-up period . CLINICAL REHABILITATION IMPACT KT may represent an effective adjunct therapy in the physical rehabilitation program of CLBP patients for immediate and acute pain control Low back pain ( LBP ) , a high prevalent condition among middle aged population , is usually associated with ' muscle spasm ' that is responsible for giving rise to pain as well as its persistence . Muscle spasm is an involuntary , painful contraction of muscles that interferes with the function and cause of muscular disorder . Therefore central ly acting skeletal muscle relaxants , also called lissive drugs , are commonly used for its treatment . Sometimes these are combined with NSAIDs . The use of central ly acting skeletal muscle relaxants , though efficacious , is associated with frequent development of dose-related adverse drug reactions like sedation , impairment of voluntary motor functions and ataxia . So there is an urgent need for newer better drugs for treatment of conditions associated with muscle spasm . The objective of this study was to assess the efficacy and safety of oral thiocolchicoside ( TC ) , a natural glycoside as compared to an adrenergic alpha 2 agonist tizanidine ( TZ ) in the Indian patients with LBP accompanied by muscle spasm . In this r and omised , non-cross over clinical study , 60 adult Indians aged between 18 and 65 years with clinical diagnosis of muscle spasm associated with low back pain were enrolled . Patients satisfying the inclusion and exclusion criteria were either treated with TC and TZ for one week duration . Visual analogue scale ( VAS ) for pain at rest and VAS for tiredness , drowsiness , dizziness and alertness was used as the self-rated primary efficacy and safety variable . Pain was also assessed by mobility assessment ; muscle spasm assessment and analgesic consumption . Data obtained from 58 patients ( those who completed the study ) indicated that in this one week study both TC and TZ provided sustained symptoms relief compared with the baseline . There was statistically significant reduction in severity of symptoms from day 0 to day 7 in both the groups . Patients were followed up on 3rd and 7th day and severity score of various parameters was recorded . There was significant difference among the treatment groups in favour of TC than TZ in efficacy parameters thus showing TC is at slightly better effective than TZ and in case of safety , TC scores significantly better over TZ in the patients with accompanying muscle spasm . These findings confirm that TC is a preferred option for the LBP with muscle spasms Study Design . Multicentric , r and omized , and controlled study of clinical evaluation of medical device in subacute low back pain . Objective . To evaluate the effects of an elastic lumbar belt on functional capacity , pain intensity in low back pain treatment , and the benefice on medical cost . Summary of Background Data . There is limited evidence of efficiency of lumbar supports for treatment of low back pain . There is also a lack of the methodology in the studies reported on the efficiency of this device . Methods . This study is r and omized , multicentric , and controlled with 2 groups : a patient group treated with a lumbar belt ( BWG ) and a control group ( CG ) . The main criteria of clinical evaluation were the physical restoration assessed with the EIFEL scale , the pain assessed by a visual analogic scale , the main economical criteria was the overall cost of associated medical treatments . Results . One hundred ninety-seven patients have participated . The results show a higher decrease in EIFEL score in BWG than CG between days 0 and 90 ( 7.6 ± 4.4 vs. de 6.1 ± 4.7;P = 0.023 ) . Respectively significant reduction in visual analogic scale was also noticed ( 41.5 ± 21.4 vs. 32.0 ± 20 ; P = 0.002 ) . Pharmacologic consumption decreased at D90 ( the proportion of patients who did not take any medication in BWG is 60.8 % vs. 40 % in CG;P = 0.029 ) . Conclusion . Lumbar belt wearing is consequent in subacute low back pain to improve significantly the functional status , the pain level , and the pharmacologic consumption . This study may be useful to underline the interest of lumbar support as a complementary and nonpharmacologic treatment beside the classic medication use in low back pain treatment OBJECTIVE The aim of this study was to compare the effect of a short-term intensive residential yoga program with physical exercise ( control ) on pain and spinal flexibility in subjects with chronic low-back pain ( CLBP ) . DESIGN This was a wait-list , r and omized controlled study . SETTING The study was conducted at a residential integrative health center in Bangalore , South India . SUBJECTS Eighty ( 80 ) subjects ( females , n = 37 ) with CLBP , who consented were r and omly assigned to receive yoga or physical exercise if they satisfied the selection criteria . INTERVENTION The intervention consisted of a 1-week intensive residential yoga program comprised of asanas ( physical postures ) design ed for back pain , pranayamas ( breathing practice s ) , meditation , and didactic and interactive sessions on philosophical concepts of yoga . The control group practice d physical exercises under a trained physiatrist and also had didactic and interactive sessions on lifestyle change . Both of the groups were matched for time on intervention and attention . OUTCOME MEASURES Pain-related outcomes were assessed by the Oswestry Disability Index ( ODI ) and by spinal flexibility , which was assessed using goniometer at pre and post intervention . Data were analyzed using repeated measures analysis of variance ( RMANOVA ) . RESULTS Data conformed to a Gaussian distribution . There was a significant reduction in ODI scores in the yoga group compared to the control group ( p = 0.01 ; effect size 1.264 ) . Spinal flexibility measures improved significantly in both groups but the yoga group had greater improvement as compared to controls on spinal flexion ( p = 0.008 ; effect size 0.146 ) , spinal extension ( p = 0.002 ; effect size 0.251 ) , right lateral flexion ( p = 0.059 ; effect size 0.006 ) ; and left lateral flexion ( p = 0.006 ; effect size 0.171 ) . CONCLUSIONS Seven ( 7 ) days of a residential intensive yoga-based lifestyle program reduced pain-related disability and improved spinal flexibility in patients with CLBP better than a physical exercise regimen Dysfunction of spinal stability seems to be one of the causes of low back pain ( LBP ) . It is thought that a large number of muscles have a role in spinal stability including the pelvic floor muscle ( PFM ) . The purpose of this study was to investigate the effect of PFM exercise in the treatment of chronic LBP . After ethical approval , a r and omized controlled clinical trial was carried out on 20 women with chronic LBP . Patients were r and omly allocated into two groups : an experimental and a control group . The control group was given routine treatment including electrotherapy and general exercises ; and the experimental group received routine treatment and additional PFM exercise . Pain intensity , functional disability and PFM strength and endurance were measured before , immediately after intervention and at 3 months follow-up . In both groups pain and functional disability were significantly reduced following treatment ( p<0.01 ) , but no significant difference was found between the two groups ( p>0.05 ) . All measurements were improved in both groups ( p<0.01 ) although patients in the experimental group showed greater improvement in PFM strength and endurance ( p<0.01 ) . It seems that the PFM exercise combined with routine treatment was not superior to routine treatment alone in patients with chronic LBP BACKGROUND Currently , there is evidence demonstrating the efficacy of stabilisation exercises in the management of acute and chronic low back disorders . However , the main facilitation techniques behind the efficacy of this exercise still remain uncertain . OBJECTIVE The purpose of the study was to investigate the changes in the plasma levels of serotonin in response to spinal stabilisation exercises in participants with chronic low back pain . METHODS Twenty-two participants ( 11 males , 11 females ) with chronic low back pain volunteered to the take part in this study . The main outcome measures used in this study were plasma levels of serotonin measured with Enzyme linked immuno absorbent assay ( ELISA ) technique . Participants were r and omly allocated either to the stabilisation exercise groups , where they carried out stabilisation exercise training or the control ( no exercise ) group . RESULTS The results showed significant increase in plasma serotonin level by 17.8 % in the exercise groups immediately following active exercise , which was not noticed in the control group . CONCLUSION It could also be that an increase in plasma serotonin levels produced with the use of stabilisation exercise may have a role to play in the positive out come of stabilisation exercise in the management of chronic low back pain The aim of this trial is to investigate and compare the effects of electrical stimulation ( ES ) program and ultrasound ( US ) therapy on pain , disability , trunk muscle strength , walking performance , spinal mobility , quality of life ( QOL ) , and depression in the patients with chronic low back pain ( CLBP ) . A total of 59 patients with definite CLBP were enrolled in this study . These patients were r and omized into three groups . Group 1 ( n = 20 ) was given an ES program and exercises . Group 2 ( n = 19 ) was given an US treatment and exercises . Group 3 ( n = 20 ) was accepted as the control group and was given only exercises . All of the programs were performed 3 days a week , for 6 weeks . The patients were evaluated according to pain , disability , walking performance , endurance , mobility , QOL , depression . The trunk muscle strength was measured with a h and -held dynamometer . All of the groups showed stastically significant improvements in pain , disability , muscle strength , endurance , walking performance , mobility , sub-scores of SF 36 , and depression when compared with their initial status . The intergroup comparison showed significant difference in physical function , energy and social function sub-groups of SF-36 , VAS pain , extensor muscle strength , between three groups . This difference was statistically significant in the groups 1 and 2 compared to the control group . There was also no significant difference between the groups 1 and 2 . We observed that US treatment and ES treatment were effective in improving pain , isometric extensor muscle strength , and QOL in patients with CLBP UNLABELLED The aim of this study was to examine whether treatments based on different theories change pain catastrophizing and internal control of pain , and whether changes in these factors mediate treatment outcome . Participants were 211 patients with nonspecific chronic low back pain ( CLBP ) participating in a r and omized controlled trial , attending active physical treatment ( APT , n = 52 ) , cognitive-behavioral treatment ( CBT , n = 55 ) , treatment combining the APT and CBT ( CT , n = 55 ) , or waiting list ( WL , n = 49 ) . Pain catastrophizing decreased in all 3 active treatment groups and not in the WL . There was no difference in the change in internal control across all 4 groups . In all the active treatment groups , patients improved regarding perceived disability , main complaints , and current pain at post-treatment , and no changes were observed in the WL group . Depression only changed significantly in the APT group . Change in pain catastrophizing mediated the reduction of disability , main complaints , and pain intensity . In the APT condition , pain catastrophizing also mediated the reduction of depression . Not only cognitive-behavioral treatments but also a physical treatment produced changes in pain catastrophizing that seemed to mediate the outcome of the treatment significantly . The implication s and limitations of these results are discussed . PERSPECTIVE This article shows that treatment elements that do not deliberately target cognitive factors can reduce pain catastrophizing . Reduction in pain catastrophizing seemed to mediate the improvement of functioning in patients with chronic low back pain . The results might contribute to the development of more effective interventions Context : In two of the earlier R and omized Control Trials on yoga for chronic lower back pain ( CLBP ) , 12 to 16 weeks of intervention were found effective in reducing pain and disability . Aim : To study the efficacy of a residential short term intensive yoga program on quality of life in CLBP . Material s and Methods : About 80 patients with CLBP ( females 37 ) registered for a week long treatment at SVYASA Holistic Health Centre in Bengaluru , India . They were r and omized into two groups ( 40 each ) . The yoga group practice d a specific module for CLBP comprising of asanas ( physical postures ) , pranayama ( breathing practice s ) , meditation and lectures on yoga philosophy . The control group practice d physical therapy exercises for back pain . Perceived stress scale ( PSS ) was used to measure baseline stress levels . Outcome measures were WHOQOL Bref for quality of life and straight leg raising test ( SLR ) using a Goniometer . Results : There were significant negative correlations ( Pearson ’s , P<0.005 , r>0.30 ) between baseline PSS with all four domains and the total score of WHOQOLBref . All the four domains ’ WHOQOLBref improved in the yoga group ( repeated measures ANOVA P=0.001 ) with significant group*time interaction ( P<0.05 ) and differences between groups ( P<0.01 ) . SLR increased in both groups ( P=0.001 ) with higher increase in yoga ( 31.1 % right , 28.4 % left ) than control ( 18.7 % right , 21.5 % left ) group with significant group*time interaction ( SLR right leg P=0.044 ) . Conclusion : In CLBP , a negative correlation exists between stress and quality of life . Yoga increases quality of life and spinal flexibility better than physical therapy exercises Abstract Objectives : To assess the influence of vitamins B1 , B6 and B12 on the analgesia success achieved by diclofenac in subjects with acute lumbago . Research design and methods : A r and omised , double blind controlled clinical study in parallel groups , in which subjects received twice-daily oral administration of either the combination therapy , Group DB ( 50 mg diclofenac plus 50 mg thiamine , 50 mg pyridoxine and 1 mg cyanocobalamin ) or diclofenac monotherapy , Group D ( 50 mg diclofenac ) . The study period lasted a maximum of 7 days . If sufficient pain reduction was achieved ( defined as Visual Analogue Scale < 20 mm and patient 's satisfaction ) , subjects could withdraw from the treatment after 3 or 5 days . All subjects gave written informed consent to participate in the study . Main outcome measures : The primary confirmatory study objective was to determine the number of patients with sufficient pain reduction after 3 days of treatment . Results : Three hundred and seventy-two subjects were allocated at r and om to either treatment group : Group DB – 187 subjects and Group D – 185 subjects . After 3 days of treatment , a statistically significant higher proportion of subjects in Group DB ( n = 87 ; 46.5 % ) than in Group D ( n = 55 ; 29 % ) terminated the study due to treatment success ( χ2 : 12.06 ; p = 0.0005 ) . Furthermore , the combination therapy yielded superior results in pain reduction , improvement of mobility and functionality . Drug safety monitoring profile throughout the trial was within the expected safety profile of diclofenac . Conclusions : The combination of diclofenac with B vitamins was superior to diclofenac monotherapy in lumbago relief after 3 days of treatment . As a study drawback , daily VAS measurements were only recorded until subject withdrawal from treatment , whether after 3 , 5 , or 7 days . There were no differences in safety profile between the two study groups Objective : To determine whether treatment with spinal manipulative therapy ( SMT ) administered in addition to st and ard care is associated with clinical ly relevant early reductions in pain and analgesic consumption . Methods : 104 patients with acute low back pain were r and omly assigned to SMT in addition to st and ard care ( n = 52 ) or st and ard care alone ( n = 52 ) . St and ard care consisted of general advice and paracetamol , diclofenac or dihydrocodeine as required . Other analgesic drugs or non-pharmacological treatments were not allowed . Primary outcomes were pain intensity assessed on the 11-point box scale ( BS-11 ) and analgesic use based on diclofenac equivalence doses during days 1–14 . An extended follow-up was performed at 6 months . Results : Pain reductions were similar in experimental and control groups , with the lower limit of the 95 % CI excluding a relevant benefit of SMT ( difference 0.5 on the BS-11 , 95 % CI −0.2 to 1.2 , p = 0.13 ) . Analgesic consumptions were also similar ( difference −18 mg diclofenac equivalents , 95 % CI −43 mg to 7 mg , p = 0.17 ) , with small initial differences diminishing over time . There were no differences between groups in any of the secondary outcomes and stratified analyses provided no evidence for potential benefits of SMT in specific patient groups . The extended follow-up showed similar patterns . Conclusions : SMT is unlikely to result in relevant early pain reduction in patients with acute low back pain The aim of this study was to evaluate the effect of a transfer technique education programme ( TT ) alone or in combination with physical fitness training ( TTPT ) compared with a control group , who followed their usual routine . Eleven clinical hospital wards were cluster r and omised to either intervention ( six wards ) or to control ( five wards ) . The intervention cluster was individually r and omised to TT ( 55 nurses ) and TTPT ( 50 nurses ) , control ( 76 nurses ) . The transfer technique programme was a 4-d course of train-the-trainers to teach transfer technique to their colleagues . The physical training consisted of supervised physical fitness training 1 h twice per week for 8 weeks . Implementing transfer technique alone or in combination with physical fitness training among a hospital nursing staff did not , when compared to a control group , show any statistical differences according to self-reported low back pain ( LBP ) , pain level , disability and sick leave at a 12-month follow-up . However , the individual r and omised intervention subgroup ( transfer technique/physical training ) significantly improved the LBP-disability ( p = 0.001 ) . Although weakened by a high withdrawal rate , teaching transfer technique to nurses in a hospital setting needs to be thoroughly considered . Other priorities such as physical training may be taken into consideration . The current study supports the findings of other studies that introducing transfer technique alone has no effect in targeting LBP . However , physical training seems to have an influence in minimising the LBP consequences and may be important in the discussion of how to prevent LBP or the recurrence of LBP among nursing personnel Aims : To investigate if a st and ardised physical exercise programme given in addition to a brief intervention at a spine clinic had an effect on return to work . Methods : A total of 246 patients sick-listed 8—12 weeks for non-specific low back pain were offered a brief intervention programme at the spine clinic with examination , information , reassurance , and encouragement to engage in physical activity as normal as possible , before they were r and omised into an intervention group ( n = 124 ) and a control group ( n = 122 ) . Patients in the intervention group participated in a physical exercise programme at the spine clinic . Results : During the 2-year follow-up , there were no significant differences between the groups on sick leave , pain , use of analgesics , psychological distress , coping strategies , fear-avoidance beliefs , self-reported disability , or walking distances . However , both groups increased return to work , reported less pain and better function , and reduced fear-avoidance beliefs for physical activity during the follow-up period . Fear-avoidance beliefs for work were not changed . Conclusions : A physical exercise programme for low back pain patients given after a brief intervention at a spine clinic did not have any additional effect on sick leave or fear-avoidance beliefs . Both groups reported less pain , better physical function , and increased return to work during follow-up . The treatment at the spine clinic did not contain a vocational rehabilitation programme directed towards individual work-related problems , which might explain no change in fear-avoidance beliefs for work OBJECTIVES To evaluate the effects of a behavioral medicine intervention , relative to an attention control , in preventing chronic pain and disability in patients with first-onset , subacute low back pain ( LBP ) with limitations in work-role function . DESIGN A 2-group , experimental design with r and omization to behavioral medicine or attention control groups . SETTING Orthopedic clinic at a Naval Medical Center . PARTICIPANTS Sixty-seven participants with first-onset LBP of 6 to 10 weeks of duration and impairment in work function , of whom 50 completed all 4 therapy sessions and follow-up 6 months after pain onset . INTERVENTION Four 1-hour individual treatment sessions of either behavioral medicine , focused on back function and pain education , self-management training , grade d activity increases , fear reduction , and pain belief change ; or attention control condition , focused on empathy , support , and reassurance . MAIN OUTCOME MEASURES The primary outcome was proportion of participants classified as recovered , according to pre-established clinical cutoffs on st and ardized measures , signifying absence of chronic pain and disability at 6 months after pain onset . Secondary analyses were conducted on pain , disability , health status , and functional work category . Intervention credibility and pain belief manipulation checks were also evaluated . RESULTS Chi square analyses comparing proportions recovered at 6 months after pain onset for behavioral medicine and attention control participants found relative rates of 52 % versus 31 % in the modified intent-to-treat sample ( P=.09 ) and 54 % versus 23 % for those completing all 4 sessions and 6-month follow-up ( P=.02 ) . At 12 months , 79 % of recovered and 68 % of chronic pain participants still met criteria for their respective groups ( P<.0001 ) . Recovered participants also had higher rates of functional work status recovery at 12 months ( recovered : 96 % full duty and 4 % light duty ; chronic pain : 61 % full duty , 18 % light duty , and 21 % medical discharge , respectively ; P=.03 ) . CONCLUSIONS Early intervention using a behavioral medicine rehabilitation approach may enhance recovery and reduce chronic pain and disability in patients with first-onset , subacute LBP . Effects are stronger for participants attending all 4 sessions and the follow-up assessment BACKGROUND Low back pain is a worldwide health problem , affecting up to 80 % of adult population . Psychological factors are involved in its development and maintenance . Many clinical trials have evaluated the efficacy of different interventions for chronic non-specific low back pain . In this field , Back School program has been demonstrated effective for people with chronic non-specific low back . AIM To evaluate the relationship between the effects of the Back School treatment and psychological features measured by MMPI-II of patients with chronic non-specific low back pain . DESIGN A r and omised controlled trial with three and six-month follow-up . SETTING Ambulatory rehabilitative university centre . POPULATION Fifty patients with chronic non-specific low back pain out of 77 screened patients . METHODS Patients were r and omly placed in a 3:2 form and were allocated into two groups ( Treatment versus Control ) . The Treatment Group participated to an intensive multidisciplinary Back School program ( BSG , N.=29 ) , while the Control Group received medical assistance ( CG , N.=21 ) . Medication was the same in both groups . Then , patients were subgrouped in those with at least an elevation in one scale of MMPI-II , and those without it . The Short Form 36 Health Status Survey for the assessment of quality of life ( primary outcome measure ) , pain Visual Analogue Scale , Waddel Index and Oswestry Disability Index were collected at baseline , at the end of treatment , and at the three and six-month follow-up . RESULTS Only the two treated subgroups showed a significant improvements in terms of quality of life , disability and pain . Among treated subjects , only those with at least one scale elevation in MMPI-II showed also a significant improvement in terms of Short Form 36 mental composite score and relevant subscores . CONCLUSION These results suggest that Back School program has positive effects , even in terms of mental components of quality of life in patients with scale elevations of MMPI-II . Probably these findings are due to its educational and cognitive-behavioural characteristics . CLINICAL REHABILITATION IMPACT Because of its educational purpose s , the Back School treatment can have positive effects also on the mental status of patients with low back pain when it affects their psychological features QUESTION Is low level laser therapy an effective adjuvant intervention for chronic low back pain ? DESIGN R and omised trial with concealed allocation , blinded assessors and intention-to-treat analysis . PARTICIPANTS Sixty-one patients who had low back pain for at least 12 weeks . INTERVENTION One group received laser therapy alone , one received laser therapy and exercise , and the third group received placebo laser therapy and exercise . Laser therapy was performed twice a week for 6 weeks . OUTCOME MEASURES Outcomes were pain severity measured using a 10-cm visual analogue scale , lumbar range of motion measured by the Schober Test and maximum active flexion , extension and lateral flexion , and disability measured with the Oswestry Disability Index on admission to the study , after 6 weeks of intervention , and after another 6 weeks of no intervention . RESULTS There was no greater effect of laser therapy compared with exercise for any outcome , at either 6 or 12 weeks . There was also no greater effect of laser therapy plus exercise compared with exercise for any outcome at 6 weeks . However , in the laser therapy plus exercise group pain had reduced by 1.8 cm ( 95 % CI 0.1 to 3.3 , p = 0.03 ) , lumbar range of movement increased by 0.9 cm ( 95 % CI 0.2 to 1.8 , p < 0.01 ) on the Schober Test and by 15 deg ( 95 % CI 5 to 25 , p < 0.01 ) of active flexion , and disability reduced by 9.4 points ( 95 % CI 2.7 to 16.0 , p = 0.03 ) more than in the exercise group at 12 weeks . CONCLUSION In chronic low back pain low level laser therapy combined with exercise is more beneficial than exercise alone in the long term OBJECTIVE To compare the short-term outcomes of active individual therapy ( AIT ) with those of a functional restoration program ( FRP ) . DESIGN Prospect i ve r and omized controlled study . SETTING Two rehabilitation centers and private ambulatory physiotherapy facilities . PARTICIPANTS One hundred thirty-two adults with chronic low back pain . Fifty-one percent of patients on sick leave or out of work ( mean duration , 180d in the 2y before treatment ) . INTERVENTIONS For 5 weeks , FRP ( at 25h/wk ) or AIT ( at 3h/wk ) . MAIN OUTCOME MEASURES Trunk flexibility , back flexor , and extensor endurance ( Ito and Sorensen tests ) , general endurance , pain intensity , Dallas Pain Question naire ( DPQ ) scores , daily activities , anxiety depression , social interest , and work and leisure activities , and self-reported improvement ( work ability , resumption of sport and leisure activities ) . RESULTS All outcome measures improved after treatment except endurance in AIT . There was no between-group difference for pain intensity or DPQ daily activities or work and leisure activities scores . Better results were observed in FRP for all other outcome measures . There was a significant effect of treatment and the initial value for the gain of the Sorensen score with a treatment or initial value interaction ; a significant effect of treatment and initial value on the gains of Ito , endurance , and DPQ social interest and anxiety depression scores , with no treatment or initial value interaction ; and a significant effect of initial value but not treatment for the gains of DPQ daily activities and work and leisure activities scores . CONCLUSIONS Low-cost ambulatory AIT is effective . The main advantage of FRP is improved endurance . We speculate that this may be linked to better self-reported work ability and more frequent resumption of sports and leisure activities Objective In controlled trials of analgesics , the primary outcome variable is most often a measure of global pain intensity . However , because pain is associated with a variety of pain sensations , the effects of analgesic treatments on different sensations could go undetected if specific pain qualities are not assessed . This study sought to evaluate the utility of assessing the multiple components of non-neuropathic pain in an analgesic clinical trial . Methods A secondary analysis was performed using data from a clinical trial involving 140 individuals with low back pain who were converted from pre study opioids to an equianalgesic dose of an extended release ( ER ) formulation of oxymorphone ( OPANA ER ) , which was then titrated to a stable dose [ defined as visual analog scale ≤40 mm ( 0 to 100 mm ) on 3 of 5 consecutive days and requiring ≤2 doses rescue medication ] . Stabilized participants were then r and omly assigned to continue with either oxymorphone ER or placebo for 12 weeks . A multidimensional measure of pain quality , the Pain Quality Assessment Scale ( PQAS ) , was administered before titration , after titration , and after treatment with oxymorphone ER or placebo . Results Significant pretitration to posttitration decreases were observed in 17 of the 20 PQAS pain descriptor items and all 3 PQAS scales . The largest effects of oxymorphone ER were found on the PQAS intense , unpleasant , deep , aching , and sharp items and the PQAS Paroxysmal and Deep scales . Discussion The results indicate that oxymorphone ER has different effects on different pain qualities of low back pain . The responsivity of the PQAS items and scales to the results of treatment with an effective and generally well-tolerated dose of an analgesic , and the ability of the PQAS items and scales to discriminate between an active analgesic and placebo , support their validity as outcome measures . The findings support the utility of using pain descriptor measures for ( 1 ) identifying the effects of pain treatments on different pain qualities and ( 2 ) targeting pain treatments to those patients who experience certain types of pain Kell , RT , and Asmundson , GJG . A comparison of two forms of periodized exercise rehabilitation programs in the management of chronic nonspecific low-back pain . J Strength Cond Res 23(2 ) : 513 - 523 , 2009-The purpose of this study was to determine the influence of 2 different periodized exercise rehabilitation programs ( resistance training [ RT ] and aerobic training [ AT ] ) on musculoskeletal health , body composition , pain , disability , and quality of life ( QOL ) in chronic ( ≥3 months ; ≥3 d·wk−1 ) nonspecific low-back pain ( CLBP ) persons . Twenty-seven CLBP subjects were r and omly assigned to 1 of 3 groups , 1 ) RT ( n = 9 ) , 2 ) AT ( n = 9 ) , or 3 ) control ( C ; n = 9 ) . Subjects were tested at baseline and at weeks 8 and 16 of training . Intensity and volume were periodized in the training groups . Significance was set at p ≤ 0.05 . No significant differences were noted among the groups at baseline . The RT group significantly decreased body fat percent from baseline to week 8 and from baseline to week 16 , whereas the AT group significantly decreased body fat percent and body mass from baseline to week 16 . The RT group significantly improved most musculoskeletal fitness , pain , disability , and QOL outcomes from baseline to week 8 , baseline to week 16 , and weeks 8 to 16 . However , the AT group showed significant improvements in flexibility from baseline to week 8 and in cardiorespiratory and peak leg power from baseline to week 8 and baseline to week 16 . The AT groups showed no significant improvements in pain , disability , or QOL . The primary finding was that periodized RT was successful at improving many fitness , pain , disability , and QOL outcome measures , whereas AT was not . This study indicates that whole-body periodized RT can be used by training and conditioning personnel in the rehabilitation of those clients suffering with CLBP OBJECTIVE To evaluate a specific workplace intervention for the management of chronic lower back pain among employees working in assembly positions in the automotive industry . DESIGN R and omized controlled trial . SETTING On site at the workplace of a French automotive manufacturer . PARTICIPANTS Subjects ( N=75 volunteers ) were recruited on site and r and omly assigned to either an experimental group ( n=37 ) or a control group ( n=38 ) . INTERVENTION The experimental group followed a supervised 60-minute session , 3 times per week , of muscle strengthening , flexibility , and endurance training during 2 months . The control group received no direct intervention . Evaluation took place at baseline , 2 months , and 6 months . MAIN OUTCOME MEASURES Pain related parameters were evaluated using vali date d question naires and scales translated into French ( Quebec Back Pain Disability Scale , Rolan Morris Disability Question naire , Dallas Pain Question naire , and the Tampa Scale for Kinesiophobia ) . Perceived pain intensity was evaluated using the numerical rating scale , and physical outcome measures were evaluated using specific indicators ( flexibility , Biering-Sorensen Test , Shirado test ) . The multivariate analysis of variance , t test , and Wilcoxon signed-rank test were used for statistical analysis . RESULTS We observed a significant beneficial effect ( P<.025 ) for the experimental group at 2 and 6 months in pain parameters , specific flexibility , and in back functions , and a significant improvement at 6 months in the control group for the perceived pain intensity , anterior flexion , flexibility of quadriceps , and Dallas Pain Question naire 's work recreational score . An increase in the practice of physical activity outside the workplace was noted in both groups at 2 months but persisted at 6 months for the experimental group . CONCLUSIONS This study reinforces the multiple health benefits of physical activity and physical therapy modalities in the workplace by assisting individuals at risk who have chronic LBP Objectives A back school is a m and atory part of the multimodal rehabilitation program for patients with chronic low back pain in Germany . However , no st and ardized and evaluated back school program has been available for routine use . In this study , we report the evaluation of a new back school that was developed based on theories of health behavior , treatment evidence , practice guidelines , and quality criteria for patient education . Methods R and omized controlled trial of patients with low back pain ( n=360 ) in inpatient orthopedic rehabilitation clinic in Germany . Intervention patients received the new back school , whereas control patients a traditional back school ( usual care ) . Illness knowledge ( primary outcome ) and secondary behavioral and health outcomes were assessed at admission , discharge , and 6 and 12 months follow-up . Results Results showed a significant medium between-group treatment effect in patients ' knowledge about back pain at discharge ( & eegr;2=0.081 ) , after 6 ( & eegr;2=0.056 ) , and 12 months ( & eegr;2=0.026 ) . Furthermore , small-to-medium effects were observed among the secondary self-management behaviors , such as physical activity , back exercises , back posture habits , and coping with pain , after 6 and 12 months . Discussion The superior effectiveness of the back school based on a biopsychosocial approach was demonstrated with regard to illness knowledge and self-management behaviors up to 1 year . Thus , the program may be recommended for dissemination within medical rehabilitation In the present study , we examined whether experimentally-manipulated attentional strategies moderated relations between pain catastrophizing and symptom-specific physiological responses to a cold-pressor task among sixty-eight chronic low back patients . Patients completed measures of pain catastrophizing and depression , and were r and omly assigned to sensory focus , distraction or suppression conditions during a cold pressor . Lumbar paraspinal and trapezius EMG , and cardiovascular responses to the cold pressor were assessed . Attentional strategies moderated the relation between pain catastrophizing and lumbar paraspinal muscle , but not trapezius muscle or cardiovascular responses . Only for participants in the suppression condition was catastrophizing related significantly to lumbar paraspinal muscle responses . Depressed affect did not account for this relation . These findings indicate that ‘ symptom-specific ’ responses among pain catastrophizers with chronic low back depend on how they attend to pain-related information . Specifically , it appears that efforts to suppress awareness of pain exaggerate muscular responses near the site of injury BACKGROUND CONTEXT Cognitive behavioral therapy has been used successfully in acute low back pain ( LBP ) treatment , but the use of a cognitive behavioral videotape as an adjunct to treatment has not been studied . PURPOSE To determine outcomes for patients with acute LBP receiving a videotape design ed to change beliefs and behaviors compared with a st and ard instructional videotape . STUDY DESIGN / SETTING R and omized controlled trial ; multidisciplinary clinic in an academic setting . PATIENT SAMPLE Consecutive subjects with less than 3 months of LBP . Of 224 eligible subjects , 138 participated and completed the initial question naires . OUTCOME MEASURES Oswestry Disability Index , Pain and Impairment Relationship Scale , Fear-Avoidance Beliefs Question naire ; medical costs related to LBP and total medical costs incurred by participants during 1 year of follow-up . METHODS Subjects were r and omly assigned to receive a behavioral videotape or a control videotape . Other than the videotape , usual care was provided to each patient . RESULTS No significant differences in any outcome measures or medical costs between the two groups at 12 months . However , baseline Vermont Disability Prediction Question naire was significantly lower in those who completed the entire study compared with those who did not complete the study . CONCLUSIONS Compared with a st and ard instructional videotape , a behavioral videotape did not change beliefs , outcomes , or costs over 1 year . Cost-effective behavioral interventions with high patient retention rates are needed , especially for those at greatest risk of high utilization of re sources Study Design . R and omized clinical trial . Objective . Compare outcomes of patients with low back pain receiving treatments matched or unmatched to their subgrouping based on initial clinical presentation . Summary of Background Data . Patients with “ nonspecific ” low back pain are often viewed as a homogeneous group , equally likely to respond to any particular intervention . Others have proposed methods for subgrouping patients as a means for determining the treatment most likely to benefit patients with particular characteristics . Methods . Patients with low back pain of less than 90 days ’ duration referred to physical therapy were examined before treatment and classified into one of three subgroups based on the type of treatment believed most likely to benefit the patient ( manipulation , stabilization exercise , or specific exercise ) . Patients were r and omly assigned to receive manipulation , stabilization exercises , or specific exercise treatment during a 4-week treatment period . Disability was assessed in the short-term ( 4 weeks ) and long-term ( 1 year ) using the Oswestry . Comparisons were made between patients receiving treatment matched to their subgroup , versus those receiving unmatched treatment . Results . A total of 123 patients participated ( mean age , 37.7 ± 10.7 years ; 45 % female ) . Patients receiving matched treatments experienced greater short- and long-term reductions in disability than those receiving unmatched treatments . After 4 weeks , the difference favoring the matched treatment group was 6.6 Oswestry points ( 95 % CI , 0.70–12.5 ) , and at long-term follow-up the difference was 8.3 points ( 95 % CI , 2.5–14.1 ) . Compliers-only analysis of long-term outcomes yielded a similar result . Conclusions . Nonspecific low back pain should not be viewed as a homogenous condition . Outcomes can be improved when subgrouping is used to guide treatment decision-making Study Design . A r and omized controlled trial . Objective . To examine the effects of the back school program on quality of life in women with chronic low back pain . Summary of Background Data . There is a controversial debate whether back school program might improve quality of life in back pain patients . This study aim ed to address this issue . Methods . One hundred and two eligible women were r and omly allocated into 2 groups . The 2 groups including back school group who received the back school program plus medication ( n = 50 ) and clinic group who received just medication ( n = 52 ) were compared at 4 points in time . Data were collected at baseline and at 3 , 6 , and 12 months follow-up using the SF-36 question naire . Repeated measures analysis was performed to compare quality of life scores in 2 groups . Results . Quality of life scores were significantly different between 2 groups throughout the study ( P < 0.0001 ) indicating a better quality of life among intervention group . Conclusion . The back school program might improve the quality of life score in women with chronic low back pain Eperisone hydrochloride ( 4'-ethyl-2-methyl-3-piperidinopropiophenone hydrochloride ) is an antispastic agent used for treatment of diseases characterized by muscle stiffness and pain . The aim of this research was to investigate the efficacy of eperisone in patients with acute low back pain and spasticity of spinal muscles . The study design was a r and omized , double-blind ( double-dummy ) study in 160 patients with low back pain and no Rx finding of major spinal diseases , r and omly assigned to a treatment with oral eperisone 100 mg three times daily ( t.i.d . ) or thiocolchicoside 8 mg twice daily ( b.i.d . ) for 12 consecutive days . Analgesic activity was evaluated by scoring " spontaneous pain " ( VAS ) and pain on movement and pression ( 4-digit scale ) , while muscle relaxant activity of the medication was evaluated by means of the " h and -to-floor " distance and the Lasegue 's manoeuvre . All the measures were done at the inclusion day and after 3 , 7 and 12 days of treatment . The two medications had comparable analgesic and muscle relaxant efficacy . Sponta-neous pain and pain on movement/pressure were significantly reduced by both treatments . Moreover , both eperisone- and thiocolchicoside-treated patients showed a clinical ly evident muscle relaxation as proved by a progressive reduction in the " h and -to-floor " distance and increase in the articular excursion ( Lasegue 's manoeuvre ) . Only 5 % of eperisone-treated patients showed minor gastrointestinal side effects , while the incidence of side effects in the thiocolchicoside group was 21.25 % . Moreover , in the thiocolchicoside-treated patients also diarrhoea was present , which reached a moderate intensity in some cases . In conclusions , eperisone represents a valuable and safer alternative to other muscle relaxant agents for treatment of low back pain BACKGROUND CONTEXT It is generally recognized that long periods of sitting can either cause or aggravate lumbar pain . A new , ergonomically design ed chair has a fixed backrest and a motor-driven seat with a horizontal rotary movement in alternating left-right cycles . PURPOSE The objective of this study is to prove superiority of the new technique of passive rotary dynamic sitting for subjects working in a sedentary occupation and suffering from lumbar pain . STUDY DESIGN / SETTING A r and omized , double-blind , multicenter , two-armed study was performed using a parallel group design . PATIENT SAMPLE 280 persons suffering from lumbar pain were matched pairwise and r and omized en bloc . OUTCOME MEASURES The first and second primary endpoints target criteria were the vali date d German version of the Oswestry Disability Index ( ODI ) and the number of days of absence from work ( DA ) attributable to lumbar pain , each based on a blinded 2-year follow-up observation after r and omization of the subjects . METHODS After inclusion in the study anonymization , the prob and s were r and omized to receive either an office chair with a motor-driven seat performing a horizontal rotary movement or a chair of the same design without the rotary seat movement . Before delivery of the chairs , 23 prob and s ( 8.2 % ) withdrew their consent to inclusion in the study without stating reasons . From 12 of the remaining matching partners , 23 new pairs were created at r and om , and the study commenced with 124 pairs . RESULTS A further 27 prob and s ( 9.6 % ) were lost to follow-up during the period up to the final consultation . This made it possible to observe the primary endpoint in 82.5 % of the prob and s. The median ODI in both groups was 53 ( 95 % confidence interval for median difference:-1.5 to 0.5 ; p=.59 ) . Median DA in both groups was 0 ( 95 % confidence interval for median difference:-infinity-+infinity ; p=1.00 ) . CONCLUSIONS Under the test conditions used in this study , passive rotary dynamic sitting was not superior to sitting in a high- quality , ergonomically design ed chair not equipped with a micro-rotation function in patients suffering from lumbar pain QUESTION Does the addition of telephone coaching to usual physiotherapy care improve activity for people with non-chronic low back pain and low to moderate recovery expectations ? DESIGN R and omised trial with concealed allocation and intention-to-treat analysis . PARTICIPANTS People attending the physiotherapy department of a public hospital for treatment within eight weeks of onset of non-specific low back pain . Eligible participants had low to moderate recovery expectations , defined as a response of 7 or less to the question ' How certain are you that you will return to all of your usual activities one month from today ? ' on a scale from 0 ( not certain at all ) to 10 ( completely certain ) . INTERVENTION Five sessions of telephone coaching by a physiotherapist trained in health coaching techniques in addition to usual physiotherapy compared to usual physiotherapy alone . OUTCOME MEASURES The Patient Specific Functional Scale , Oswestry Disability Index , Pain Self Efficacy Question naire , and recovery expectation were measured at baseline , 4 , and 12 weeks . RESULTS 30 participants were recruited , with 26 completing all measures at 12 weeks . There were no significant differences between groups at 4 weeks . After 12 weeks the coaching group improved significantly more than the control group on two 10-point scales : the Patient Specific Functional Scale ( mean difference 3.0 points , 95 % CI 0.7 to 5.4 ) and recovery expectation ( mean difference 3.4 points , 95 % CI 1.1 to 5.7 ) . Estimates of effect sizes were moderate to large in favour of the intervention . CONCLUSION The addition of telephone health coaching to usual physiotherapy care for people with non-chronic non-specific low back pain led to clinical ly important improvements in activity and recovery expectation . TRIAL REGISTRATION ACTRN12607000458437 Background and Purpose : The purpose of this multicenter r and omized clinical trial was to examine the effectiveness of an extension-oriented treatment approach ( EOTA ) in a subgroup of subjects with low back pain ( LBP ) who were hypothesized to benefit from the treatment compared with similar subjects who received a lumbar spine strengthening exercise program . Methods : Subjects with LBP and symptoms distal to the buttocks that central ized with extension movements were included . Forty-eight subjects were r and omly assigned to groups that received an EOTA ( n=26 ) or a strengthening exercise program ( n=22 ) . Subjects attended 8 physical therapy sessions and completed a home exercise program . Follow-up data were obtained at 1 week , 4 weeks , and 6 months after r and omization . Primary outcome measures were disability ( modified Oswestry Low Back Pain Disability Question naire ) and pain ( Numeric Pain Rating Scale ) . Results : Subjects in the EOTA group experienced greater improvements in disability compared with subjects who received trunk strengthening exercises at 1 week ( mean difference between groups from baseline=8.9 , 95 % confidence interval [CI]=2.0 , 15.9 ) , 4 weeks , ( mean difference=14.4 , 95 % CI=4.8 , 23.9 ) , and 6 months ( mean difference=14.6 , 95 % CI=4.6 , 24.6 ) . The EOTA group demonstrated greater change in pain at the 1-week follow-up only . Discussion and Conclusion : An EOTA was more effective than trunk strengthening exercise in a subgroup of subjects hypothesized to benefit from this treatment approach . Additional research is needed to explore whether an EOTA may benefit other subgroups of patients Context Exercise and advice are common treatments for patients with subacute low back pain , but their effectiveness is unclear . Contribution In this trial , 259 adults with subacute low back pain received 12 real or sham physiotherapist-directed exercise sessions and 3 real or sham advice sessions over 6 weeks . Compared with sham exercise and sham advice , patients who received real exercise and real advice had the most benefit at 6 weeks . However , only a small benefit on patient-reported function persisted at 12 months . Implication Compared with no exercise or advice , a combination of physiotherapist-directed exercise and advice seems to improve pain and function in the short term for patients with subacute low back pain . The Editors Back pain is 1 of the most frequent reasons for consultation with a general practitioner ( 1 , 2 ) . Most treatment guidelines provide advice for patients on managing acute or recent-onset low back pain but not chronic pain ( 3 ) . This reflects the view that acute low back pain is typically self-limited and that only a small proportion of persons develop chronic pain . However , a recent systematic review of the prognosis of acute low back pain ( 4 ) showed that this view is inaccurate : Pain and disability are typically ongoing , and recurrences are common . Thus , effective treatments for patients whose pain and disability persist beyond the acute phase are needed . We are interested in the subacute phase , which is the transition period from acute ( duration < 6 weeks ) to chronic ( duration > 3 months ) low back pain . All treatment guidelines ( 3 ) endorse advice as a treatment for subacute low back pain , and advice is the most frequently administered treatment in general practice ( 1 ) . Exercise is the most common treatment for low back pain ( 2 , 5 , 6 ) , and some guidelines recommend it for subacute low back pain ( 3 ) . However , a systematic review of treatment for subacute low back pain ( 7 ) concluded that no high- quality evidence exists for the efficacy of any intervention . To address this knowledge gap , we conducted a factorial r and omized , placebo-controlled trial of the effect of exercise , advice , or both on pain , function , and global perceived effect . Methods Setting The trial was conducted at 7 physiotherapy clinics in Australia and New Zeal and , of which 6 were in university teaching hospitals and 1 was in a primary care clinic . There were 16 physiotherapists . Each clinic had 1 to 5 therapists providing treatment . We enrolled participants from January 2001 to June 2003 . The study protocol was approved by the institutional review boards of the University of Sydney , Sydney , Australia , and of each clinic . Participants We sought persons between 18 and 80 years of age with nonspecific low back pain lasting for at least 6 weeks but no longer than 12 weeks . Participants were recruited by direct referral to the trial by a health care professional ( n= 1 ) , invitations to patients on hospital waiting lists for physiotherapy treatment of low back pain ( n= 73 ) , and advertisements in newspapers ( n= 185 ) . Exclusion criteria were spinal surgery in the past 12 months , pregnancy , nerve root compromise , confirmed or suspected serious spinal abnormality ( for example , infection , fracture , or the cauda equina syndrome ) , contraindications to exercise , and poor comprehension of the English language . We did not exclude participants who were receiving low back pain treatment other than spinal surgery . Potential participants who reported osteoarthritis ; spondylitis ; spondylolysis ; spondylolisthesis ; disc protrusion , herniation , or prolapse ; or spinal stenosis were eligible . We asked participants not to take other treatments for low back pain during the 6-week treatment phase . Written informed consent was obtained from all participants before they enrolled in the trial . R and omization and Interventions After completing the baseline assessment , we r and omly allocated participants to 1 of 4 intervention groups : exercise and advice , exercise and sham advice , sham exercise and advice , or sham exercise and sham advice . The allocation schedule was generated by using the r and om-number function in Microsoft Excel ( Microsoft , Inc. , Redmond , Washington ) , and the allocation codes were placed in sequentially numbered , sealed , opaque envelopes . At each site , the trial coordinator or the physiotherapist allocated participants to groups by opening the next numbered envelope . This process ensured that allocation was concealed from participants , referring medical practitioners , trial staff who determined eligibility , and the assessor of outcomes . The 12 exercise or sham exercise sessions were delivered over 6 weeks : 3 sessions per week in weeks 1 and 2 , 2 sessions per week in weeks 3 and 4 , and 1 session per week in weeks 5 and 6 . In weeks 1 , 2 , and 4 , participants also received advice or sham advice . Sham treatments were design ed to provide similar contact time with the treating clinician . The clinicians who provided the sham treatments were the same ones who provided the real treatments . Registered physiotherapists who received training from an experienced clinical psychologist delivered treatment . Treatment consistency was promoted at the initial staff meeting and at regular trial treatment meetings , and by providing a treatment manual to all treatment providers . To assess treatment validity , an investigator recorded and assessed sample treatment sessions . In addition , 1 investigator regularly visited each treatment site to monitor delivery of treatment . The comprehensive treatment manual is in the Appendix . Appendix . Treatment Manual Exercise The exercise program was based on the program described by Lindstrm and colleagues ( 8) . It included an individualized , progressive , submaximal program design ed to improve the abilities of participants to complete functional activities that they specified as being difficult to perform because of low back pain . Each participant undertook aerobic exercise ( for example , a walking or cycling program ) ; stretches ; functional activities ; activities to build speed , endurance , and coordination ; and trunk- and limb-strengthening exercises . Physiotherapists used principles of cognitive-behavioral therapy , including setting goals of progressively increasing difficulty , encouraging self-monitoring of progress , and promoting self-reinforcement ( 9 ) . Physiotherapists provided individualized home exercise programs , which they regularly review ed , and they encouraged continuation of the home program after the intervention finished . Sham Exercise The control for the exercise intervention consisted of sham pulsed ultrasonography ( 5 minutes ) and sham pulsed short-wave diathermy ( 20 minutes ) . The sham units were identical to active units ( for example , the on and off lights illuminated and the output dial moved ) except that they did not provide output . To optimize treatment credibility , physiotherapists followed the usual clinical routine for delivering these treatments . The active forms of these treatments delivered in pulsed mode do not produce heat ; thus , previous experience with the treatments would not unblind participants . Participants allocated to exercise did not receive the active forms of these treatments . Advice Advice sessions were based on the program by Indahl and colleagues ( 10 ) and aim ed to encourage a grade d return to normal activities . The physiotherapist explained the benign nature of low back pain , addressed any unhelpful beliefs about back pain , and emphasized that being overly careful and avoiding light activity would delay recovery . Sham Advice During sham advice sessions , participants were given the opportunity to talk about their low back pain and any other problems . The physiotherapist responded in a warm and empathic manner , displaying genuine interest in the participant , but did not give advice about the low back pain ( 11 ) . Participants were told that the trial included active and placebo physiotherapy treatments and that they would receive 2 treatments , but they were not told whether the interventions they received were active or sham . Outcomes and Measurements We determined participants ' perceptions of the effectiveness of treatment at the beginning of the trial and at 12 months . We assessed treatment adherence by the number of appointments attended , session duration , and amount of time the physiotherapist spent with each participant . Participants were asked not to seek other treatments during the 6-week treatment period . Participants who discontinued treatment were encouraged to return for follow-up . Immediately before r and omization , we obtained baseline measurements . We collected additional data on work status , medication use , side effects , adverse events , and number and type of co- interventions at 6 weeks , 3 months , and 12 months after r and omization . We chose primary and secondary outcomes a priori . The primary outcomes were pain , global perceived effect , and functional ability at 6 weeks and 12 months . Secondary outcomes were pain , global perceived effect , and functional ability at 3 months ; number of health care contacts during the past 6 weeks ( determined at 12 months ) ; and disability and depression at 6 weeks , 3 months , and 12 months . We rated pain as average pain over the past week on a scale of 0 ( no pain ) to 10 ( worst pain possible ) ( 12 ) . We measured functional ability by using the Patient-Specific Functional Scale ( score range , 0 [ can not perform activity ] to 10 [ can perform activity at preinjury level ] ) ( 13 ) . We measured global perceived effect of treatment on an 11-point scale , ranging from 5 ( vastly worse ) to 5 ( completely recovered ) , with 0 being no change . We measured disability with the Rol and Morris Disability Question naire ( score range , 0 to 24 ) ( 14 ) . We measured depression , anxiety , and stress by using the 21-item Depression Anxiety Stress Scales ( DASS-21 ) ( score range for each subscale , 0 to 42 ) ( 15 ) . These measures have acceptable psychometric properties and are widely used in Objectives . The development of multicontact electrodes and programmable , implanted pulse generators has increased the therapeutic success of spinal cord stimulation ( SCS ) by enhancing the ability to capture and maintain pain/paresthesia overlap . This study sought to determine if interleaved stimulation and /or frequency doubling improves pain/paresthesia overlap in patients with failed back surgery syndrome . Methods . Using a patient-interactive computer system that quantifies SCS performance and presents stimulation setting s in r and omized , double-blind fashion , we compared the effect on pain/paresthesia overlap of interleaved stimulation ( rapidly interleaved pulse trains using two different contact combinations ) vs. st and ard treatment with a single contact combination , controlling for frequency doubling . Stimulation amplitude ( charge per phase , as determined by varying pulse voltage or width ) was adjusted to a subjectively comfortable intensity ( usage amplitude ) , which was maintained for all trials in each patient . The number of percutaneous spinal electrodes used ( one or two ) and the phase angle between interleaved pulses were additional study variables . Results . Multivariate analysis of 266 test results from 15 patients revealed a statistically significant ( p ≤ 0.05 ) association between increased computer-calculated pain/paresthesia overlap and 1 ) high- and low-frequency interleaved stimulation using two combinations of contacts and 2 ) frequency doubling using one combination . We found no significant effect for electrode configuration ( single or dual ) , pulse width matching , or phase angle . Conclusions . The statistically significant advantages we observed for SCS with interleaved stimulation are explained , at least in part , by the effects of frequency doubling . These findings have important implication s for the design and adjustment of pulse generators OBJECTIVE This study compared the dynamic surface electromyographic ( EMG ) activities of back muscles and pain before and after traditional bone setting and physical therapy . METHODS This study was a prospect i ve clinical trial that compared surface EMG dynamic activities after traditional bone setting and physical therapy . Sixty-one patients ( mean age , 41 years ) with nonspecific low back pain were r and omized into two subgroups by treatment . The patients underwent a dynamic EMG evaluation for which they were asked to st and and then bend forward as far as possible , stay fully flexed , and return to st and ing . A flexion-relaxation ratio was calculated by comparing maximal EMG activity while flexing with the average EMG activity in full flexion . Concentric ( maximal EMG activity during extension ) and eccentric ( maximal EMG activity during flexion ) ratios were also used in the analyses . RESULTS Disability , depression , and visual analog scale scores decreased significantly after both treatments . The concentric ratio increased statistically in both groups after the treatments . The study failed to show a significant association between experienced back pain and EMG parameters . CONCLUSIONS Both treatments seem to have a positive influence on back muscle function by improving muscle symmetry ; however , the treatments had no effect on the flexion-relaxation phenomenon after 1 month . Active back exercise at home together with rehabilitation treatments might be effective and improve function for patients with chronic low back pain The objective of the study was to examine the effectiveness of auriculotherapy using magnetic pellets for the elderly suffering from low back pain ( LBP ) . Sixty participants who were 60-years old or above and had been suffering from LBP were recruited . Participants were r and omly allocated to receive auriculotherapy on a 3-week basis using either Semen Vaccariae ( control group=30 ) or magnetic pellets ( experimental group=30 ) . Seven auricular acupoints that are believed to have an effect on LBP were selected . Treatment effects were evaluated using the Chinese Pain Intensity Verbal Rating scale ( VRS ) . The experimental group had indeed experienced a significant improvement in pain relief when compared with the control group ; and the therapeutic effects were sustained at 2 and 4-week follow-up periods after the therapy . Findings of this study demonstrated that auriculotherapy using magnetic pellets significantly reduce the pain intensity level of the elderly suffering from non-specific LBP BACKGROUND Few studies have evaluated the effectiveness of massage for chronic low back pain . OBJECTIVE To compare the effectiveness of 2 types of massage and usual care for chronic back pain . DESIGN Parallel-group r and omized , controlled trial . R and omization was computer-generated , with central ized allocation concealment . Participants were blinded to massage type but not to assignment to massage versus usual care . Massage therapists were unblinded . The study personnel who assessed outcomes were blinded to treatment assignment . ( Clinical Trials.gov registration number : NCT00371384 ) SETTING An integrated health care delivery system in the Seattle area . PATIENTS 401 persons 20 to 65 years of age with nonspecific chronic low back pain . INTERVENTION Structural massage ( n = 132 ) , relaxation massage ( n = 136 ) , or usual care ( n = 133 ) . MEASUREMENTS Rol and Disability Question naire ( RDQ ) and symptom bothersomeness scores at 10 weeks ( primary outcome ) and at 26 and 52 weeks ( secondary outcomes ) . Mean group differences of at least 2 points on the RDQ and at least 1.5 points on the symptom bothersomeness scale were considered clinical ly meaningful . RESULTS The massage groups had similar functional outcomes at 10 weeks . The adjusted mean RDQ score was 2.9 points ( 95 % CI , 1.8 to 4.0 points ) lower in the relaxation group and 2.5 points ( CI , 1.4 to 3.5 points ) lower in the structural massage group than in the usual care group , and adjusted mean symptom bothersomeness scores were 1.7 points ( CI , 1.2 to 2.2 points ) lower with relaxation massage and 1.4 points ( CI , 0.8 to 1.9 points ) lower with structural massage . The beneficial effects of relaxation massage on function ( but not on symptom reduction ) persisted at 52 weeks but were small . LIMITATION Participants were not blinded to treatment . CONCLUSION Massage therapy may be effective for treatment of chronic back pain , with benefits lasting at least 6 months . No clinical ly meaningful difference between relaxation and structural massage was observed in terms of relieving disability or symptoms . PRIMARY FUNDING SOURCE National Center for Complementary and Alternative Medicine BACKGROUND In recent years , disability due to chronic low back pain ( LBP ) has steadily increased in all industrialized countries . In the treatment of chronic LBP , the objectives are to reduce pain , to improve function and minimize avoiding behavior . Exercise therapy is a management strategy that is widely used as a treatment for LBP . AIM The aim of this study was to investigate the effects of high- intensity aerobic exercise on pain , disability , anxiety or depression in people with chronic LBP . DESIGN This was a r and omized controlled trial SETTING Institute of Occupational Medicine , Department of Physical Medicine and Rehabilitation - Outpatient Ward POPULATION Kosovo power plant workers . METHODS Participants with chronic low back pain , excluding those with " red flag " criteria were assigned r and omly to one of the two treatment groups : an aerobic exercise group ( N.=50 ) , and an passive modalities group ( N.=51 ) . Data on low back pain intensity ( visual analogue scale ) , disability ( Oswestry Low Back Pain Disability Question naire ) , fingertip-to-floor distance , and psychosocial factors ( Hospital Anxiety and Depression Scale ) were collected at baseline and after 12-weeks follow-up points . RESULTS At 12-week follow-up , significant improvements in pain intensity and disability had occurred in the exercise group . We have verified significant improvements in comparison with basic values in pain intensity ( 6 ± 2.6 vs. 2 ± 1.7 , diff . of mean=3.9 , P < 0.001 ) , disability ( 31 ± 17.4 vs. 15.8 ± 12.7 , diff . of mean=15.2 , P<0.001 ) , anxiety and depression ( 21.1 ± 8.2 vs. 14 ± 6.7 , diff . of mean=7.1 , P < 0.001 ) , and fingertip- to-floor distance ( 27.8 ± -9.1 vs. 14.2 ± -5.7 , P<0.001 ) . Whereas , differences in average pain , disability , anxiety and depression and fingertip-to-floor distance are not significant in the control group . CONCLUSION High intensity aerobic exercise reduces pain , disability and psychological strain in patients with chronic low back pain . CLINICAL REHABILITATION IMPACT This research is important for the fact that High Intensity Aerobic Exercise Programs are not so exploited in the current available literature for the treatment of LBP . Therefore , this is another modest contribution which can reinforce the need for more frequent use of High Intensity Aerobic Exercise Programs in the treatment of LBP Objective : The objectives of this study were to assess the effect of unstable s and als on ( 1 ) low back pain ( LBP ) in golfers with undiagnosed moderate LBP , ( 2 ) static and dynamic balance , and ( 3 ) golf performance . Design : This was a 6-week prospect i ve study where subjects were r and omized to a control group and an intervention group . Setting : Baseline measurements were recorded in the Human Performance Laboratory . Participants : Forty male golfers with nonspecific moderate LBP . Intervention : The intervention group wore unstable shoes for 6 weeks , and the control group wore their regular golf shoes . Main Outcome Measures : Low back pain , timed balance , and golf performance were assessed at baseline and at 6 weeks . Changes were compared through independent sample s t tests . Results : ( 1 ) There was a significant difference between groups in the change of perceived LBP scores in the laboratory ( test group : −17.5/100 mm , control : −3.6/100 mm ) and in the comparison of the first week entries to the last week entries recorded in logbooks ( test group : −10.7/100 mm , control group : + 2.6/100 mm ) . ( 2 ) There was no significant change in the static or dynamic balance times . ( 3 ) There was no significant change in golf performance between the intervention and control groups . Conclusion : The results indicate that unstable s and als can be used to reduce moderate lower back pain in this population of golfers without negatively affecting performance Background : Escitalopram has never been demonstrated to be useful in the treatment of chronic low back pain ( CLBP ) , while duloxetine has demonstrated analgesic effect in chronic pain states . The aim of this trial was to examine the efficacy of escitalopram for the treatment of CLBP compared with duloxetine . Methods : A total of 85 adult patients with non-radicular CLBP entered a 13-week r and omized study comparing escitalopram 20 mg with duloxetine 60 mg once daily . The primary measure was comparison of the two drugs on reduction in weekly mean 24-h average pain . Secondary measures included Clinical Global Impressions of Severity ( CGI-S ) and the 36-item Short-Form Health Survey ( SF-36 ) . Results : Eighty patients ( n = 39 escitalopram , n = 41 duloxetine ) completed the study . No significant differences existed between escitalopram and duloxetine on reduction in weekly mean 24-h average pain at end point . Both escitalopram and duloxetine demonstrated significant improvement on CGI-S and SF-36 . Conclusions : Escitalopram and duloxetine demonstrated efficacy and safety in the management of CLBP , with no significant differences . Results of this study should be replicated in a larger sample of patients Question Is transcutaneous nerve stimulation ( TENS ) effective in the management of chronic low back pain ? Data sources Trials were located by search es of Medline , Embase , Cochrane Central Register of Controlled Trials , and PEDro , review of the reference list of relevant articles , and by contact with experts in the field . Study selection and assessment R and omised controlled trials with more than 5 participants per arm were eligible for inclusion . Trials were additionally restricted to those enrolling patients with non-specific LBP with or without sciatica with duration of symptoms greater than 12 weeks in an outpatient setting . All st and ard modes of TENS were eligible . Acupuncture TENS and neuromuscular stimulation were excluded . Outcomes Eligible outcomes included pain , disability , well being , work loss , and side effects of treatment . Results were expressed as weighted mean differences ( WMD ) for continuous data . Main results The literature search revealed 39 potentially eligible studies but only two , Cheing 1999 and Deyo 1990 , fulfilled all eligibility criteria . Both trials compared active TENS to placebo , however only the Deyo study excluded subjects with previous experience of TENS to assist treatment blinding . The Cheing study reported greater reduction in pain ( expressed as % of baseline ) one hour following a single one hour treatment with active TENS : WMD=–33.6 % ( –53.27 % to –13.97 % ) ; but did not measure beyond this time point or measure other outcomes . The Deyo study reported that a one month course of active TENS was no more effective than placebo at one month follow-up for pain intensity , pain frequency , pain improvement , functional status , and self-rated activity level . For pain intensity ( measured on a 0–100 mm VAS ) the WMD was –2.3 mm ( –9.5 to 5 ) ; for pain improvement ( 1 = entirely gone , 6=much worse ) WMD=0.0 ( –0.4 to 0.4 ) and for functional status ( range 0–100 with higher scores indicating worse function ) WMD=–0.5 ( –2.3 to 1.3 ) . Conclusions Because of conflicting results the efficacy of TENS in the treatment of chronic low back pain is unclear CONTEXT Individuals with low back pain ( LBP ) are thought to benefit from interventions that improve motor control of the lumbopelvic region . It is unknown if therapeutic exercise can acutely facilitate activation of lateral abdominal musculature . OBJECTIVE To investigate the ability of 2 types of bridging-exercise progressions to facilitate lateral abdominal muscles during an abdominal drawing-in maneuver ( ADIM ) in individuals with LBP . DESIGN R and omized control trial . SETTING University research laboratory . PARTICIPANTS 51 adults ( mean ± SD age 23.1 ± 6.0 y , height 173.6 ± 10.5 cm , mass 74.7 ± 14.5 kg , and 64.7 % female ) with LBP . All participants met 3 of 4 criteria for stabilization-classification LBP or at least 6 best-fit criteria for stabilization classification . INTERVENTIONS Participants were r and omly assigned to either traditional-bridge progression or suspension-exercise-bridge progression , each with 4 levels of progressive difficulty . They performed 5 repetitions at each level and were progressed based on specific criteria . MAIN OUTCOME MEASURES Muscle thickness of the external oblique ( EO ) , internal oblique ( IO ) , and transversus abdominis ( TrA ) was measured during an ADIM using ultrasound imaging preintervention and postintervention . A contraction ratio ( contracted thickness : resting thickness ) of the EO , IO , and TrA was used to quantify changes in muscle thickness . RESULTS There was not a significant increase in EO ( F1,47 = 0.44 , P = .51 ) or IO ( F1,47 = .30 , P = .59 ) contraction ratios after the exercise progression . There was a significant ( F1,47 = 4.05 , P = .05 ) group-by-time interaction wherein the traditional-bridge progression ( pre = 1.55 ± 0.22 ; post = 1.65 ± 0.21 ) result ed in greater ( P = .03 ) TrA contraction ratio after exercise than the suspension-exercise-bridge progression ( pre = 1.61 ± 0.31 ; post = 1.58 ± 0.28 ) . CONCLUSION A single exercise progression did not acutely improve muscle thickness of the EO and IO . The magnitude of change in TrA muscle thickness after the traditional-bridging progression was less than the minimal detectable change , thus not clinical ly significant QUESTION What is the effect of early physiotherapy intervention on pain and patient satisfaction in acute low back pain ? DESIGN R and omised trial with concealed allocation , assessor blinding , and intention-to-treat analysis . PARTICIPANTS 110 patients attending the Accident and Emergency Department of a local acute hospital . INTERVENTION The experimental group received early physiotherapy intervention which consisted of education , reassurance , pain management , mobility training , interferential therapy , walking training , and walking aids as indicated . The control group received only walking training and walking aids as indicated . All participants received conventional medical intervention and outpatient physiotherapy intervention . OUTCOME MEASURES Pain was measured using the Numeric Pain Rating Scale and satisfaction was measured using the Numeric Global Rating of Change Scale at baseline , discharge from the Accident and Emergency Department , admission to the Physiotherapy Outpatient Department , 1 month , 3 months , and 6 months . RESULTS Participants in the experimental group had 1.6 out of 10 points ( 97.5 % CI 0.8 to 2.3 ) less pain than the control group on discharge from the Accident and Emergency Department and still had 0.9 points ( 97.5 % CI 0.1 to 1.6 ) less pain on admission to the Physiotherapy Outpatient Department . Participants in the experimental group were 2.1 out of 20 points ( 97.5 % CI 1.2 to 2.9 ) more satisfied than the control group on discharge from the Accident and Emergency Department . CONCLUSION Early physiotherapy intervention was effective in reducing pain and increasing satisfaction for patients with acute low back pain in an Accident and Emergency Department but the effect tailed off Study Design . A stratified r and omized single-blinded clinical trial . Objective . To compare the efficacies of 2 active therapies for chronic low back pain ( CLBP ) . Summary of Background Data . Both a multidisciplinary biopsychosocial rehabilitation program and an intensive individual therapist-assisted back muscle strengthening exercise program used in Denmark have been reported to be effective for the treatment of CLBP . Methods . A total of 286 patients with CLBP were r and omized to either a group-based 12-week program comprising 73 hours of therapist exposure ( approximately 12 h/patient ) : 35 hours of hard physical exercise , 22 hours of light exercise/occupational therapy , and 16 hours of education ( group A ) or a 12-week program comprising 1 hour of personal training twice a week , i.e. , therapist exposure 24 h/patient ( group B ) . At baseline and at 3 , 6 , 12 , and 24 months , patients filled out question naires on pain ( visual analogue scale [VAS]-pain average , which was the primary outcome measure ) , Rol and -Morris disability question naire , global perceived outcome , and 36-Item Short-Form General Health Survey . Data were analyzed using the intention-to-treat principle . Results . Of the 286 patients , 14 patients did not start treatment . Of the remaining patients , 25 ( 9 % ) dropped out of therapy . The 2 groups were comparable regarding baseline characteristic . After treatment , significant improvements were observed with regard to pain , disability , and most of the quality of life dimensions . These effects were sustained over the 24-month follow-up period . There were some statistically significant differences between the 2 groups relating to secondary end points , Rol and -Morris disability question naire , and in the MOS 36-Item Short-Form Health Survey the “ physical functioning ” dimension and the “ physical component summary . ” Conclusion . Both groups showed long-term improvements in pain and disability scores , with only minor statistically significant differences between the 2 groups . The minor outcome difference in favor of the group-based multidisciplinary rehabilitation program is hardly of clinical interest for individual patients Background The purpose of this study was to examine the immediate effect of single acupuncture stimulation to the most painful point in patients with low back pain . Method A r and omised , evaluator-blinded , sham controlled clinical trial was conducted in which 31 patients with low back pain were r and omly allocated to either an acupuncture group ( n=15 ) or a sham acupuncture group ( n=16 ) . Both acupuncture and sham acupuncture were performed at the most painful point on the lower back of the subjects . For the acupuncture group , a stainless steel needle was inserted to a depth of 20 mm and manually stimulated ( sparrow pecking method ) for 20 seconds , while for the sham treatment a guide tube without a needle was placed at the point and tapped on the skin . Changes in low back pain were evaluated with a visual analogue scale ( VAS ) and the Schober test . Participants were also asked if they felt the needling sensation or not . The therapy and the evaluation were independently performed by two different acupuncturists . Results VAS score and the Schober test score showed significant improvement after treatment as compared with the sham group ( P=0.02 , 0.001 , respectively ) . There were no significant differences in the needling sensation between the acupuncture and sham group . Conclusion These results suggest that acupuncture at the most painful point gives immediate relief of low back pain Kumar , S , Sharma , VP , and Negi , MPS . Efficacy of dynamic muscular stabilization techniques ( DMST ) over conventional techniques in rehabilitation of chronic low back pain . J Strength Cond Res 23(9 ) : 2651 - 2659 , 2009-Low back pain ( LBP ) is a common health problems . Although it is multifactorial , its treatment varies considerably , including medication , physical therapy modalities , and exercise therapy , and each have several interventions . Despite their effectiveness , their head-to-head comparisons are limited . This study was aim ed at 1 such comparison . A total of 30 hockey players , 18 to 28 years of age , with subacute or chronic LBP were r and omly assigned equally in 2 groups . One group was treated with conventional treatment-a combination of 2 electrotherapies ( ultrasound and short-wave diathermy ) and 1 exercise therapy ( lumbar strengthening exercises)- and the other group was treated with dynamic muscular stabilization techniques ( DMST ) , an active approach of stabilizing training . The results showed that both the treatments are effective in the management of LBP , but DMST was found to be more effective than conventional treatment . The walking , st and ups , climbing , and pain improved 4.7 , 2.0 , 1.4 , and 2.1 times , respectively , more with DMST than with conventional treatment . With time ( days ) , walking , st and ups , climbing , and pain improved ( correlation ) significantly ( p < 0.01 ) higher in DMST ( r = 0.83 to 0.92 ) than in conventional treatment ( r = 0.40 to 0.75 ) , and their rate of improvement ( regression β coefficients ) were also significantly ( p < 0.01 ) higher in DMST ( β = −0.16 to 0.73 ) than in conventional treatment ( β = −0.07 to 0.15 ) . Subjects matching were perfect ( p < 0.01 ) and test-retest reliability of all dependent variables was significantly ( p < 0.01 ) high ( intraclass correlation coefficient ≈ 1 ) . No major adverse effects were recorded in any of the patients in either group . This study concluded that for early recovery , DMST is more suitable than conventional treatment OBJECTIVE Chiropractic care is used by many older patients for low back pain ( LBP ) , but there are no published results of r and omized trials examining spinal manipulation ( SM ) for older adults . The purpose of this study was to compare the effects of 2 biomechanically distinct forms of SM and minimal conservative medical care ( MCMC ) for participants at least 55 years old with subacute or chronic nonradicular LBP . METHODS R and omized controlled trial . The primary outcome variable was low back-related disability assessed with the 24-item Rol and Morris Disability question naire at 3 , 6 , 12 , and 24 weeks . Participants were r and omly allocated to 6 weeks of care including 12 visits of either high-velocity , low-amplitude (HVLA)-SM , low-velocity , variable-amplitude (LVVA)-SM , or 3 visits of MCMC . RESULTS Two hundred forty participants ( 105 women and 135 men ) ages 63.1 + /- 6.7 years without significant comorbidities . Adjusted mean Rol and Morris Disability change scores ( 95 % confidence intervals ) from baseline to the end of active care were 2.9 ( 2.2 , 3.6 ) and 2.7 ( 2.0 , 3.3 ) in the LVVA-SM and HVLA-SM groups , respectively , and 1.6 ( 0.5 , 2.8 ) in the MCMC group . There were no significant differences between LVVA-SM and HVLA-SM at any of the end points . The LVVA-SM group had significant improvements in mean functional status ranging from 1.3 to 2.2 points over the MCMC group . There were no serious adverse events associated with any of the interventions . CONCLUSIONS Biomechanically distinct forms of SM did not lead to different outcomes in older LBP patients and both SM procedures were associated with small yet clinical ly important changes in functional status by the end of treatment for this relatively healthy older population . Participants who received either form of SM had improvements on average in functional status ranging from 1 to 2.2 over those who received MCMC . From an evidence -based care perspective , patient preference and clinical experience should drive how clinicians and patients make the SM procedure decision for this patient population OBJECTIVE Previous work suggests that elevated trait anger-out exacerbates pain responses in part through endogenous opioid dysfunction . The authors examined whether this opioid dysfunction affects not only perceived pain intensity , but also emotional responses to being hurt . DESIGN 79 chronic low back pain ( LBP ) patients and 46 healthy controls received opioid blockade ( 8 mg naloxone i.v . ) and placebo in r and omized , counterbalanced order in separate sessions . During each session , participants sequentially experienced finger pressure pain and ischemic forearm pain tasks , with emotional state assessed at baseline and postpain . MAIN OUTCOME MEASURES Blockade effects indexing opioid modulation of emotional reactivity were derived by subtracting placebo from blockade condition emotional reactivity . RESULTS Significant Participant Type x Anger-Out interactions on blockade effects indicated that in LBP participants but not in controls , greater anger-out was associated with deficient opioid modulation of anxiety , anger , and fear reactivity to noxious stimulation . Across participant types , greater anger-in was associated with impaired opioid modulation of anxiety and fear reactivity . Anger-in opioid effects were partially due to overlap with general negative affect . CONCLUSIONS Opioid dysfunction associated with trait anger-out may affect not only perceived pain intensity , but also pain-related suffering in individuals with chronic pain conditions . Implication s for underst and ing the health effects of anger management styles are discussed Many treatment options for chronic low back pain are available , including varied forms of electric stimulation . But little is known about the electricity effect between electro-acupuncture and pulsed radiofrequency . The objective of this study is to assess the difference in effectiveness of pain relief between pulsed radiofrequency and electro-acupuncture . Visual analog score ( VAS ) pain score , the Oswestry disability index ( ODI ) to measure a patient 's permanent functional disability , and Short form 36 ( SF-36 ) which is a survey used in health assessment to determine the cost-effectiveness of a health treatment , were used as rating systems to measure the pain relief and functional improvement effect of pulsed radiofrequency and electro-acupuncture , based on the method ological quality of the r and omized controlled trials , the relevance between the study groups , and the consistency of the outcome evaluation . First , the baseline status before therapy shows no age and gender influence in the SF-36 and VAS score but it is significant in the ODI question naire . From ANOVA analyses , it is apparent that radiofrequency therapy is a significant improvement over electro-acupuncture therapy after one month . But electro-acupuncture also showed functional improvement in the lumbar spine from the ODI . This study provides sufficient evidence of the superiority of pulsed radiofrequency ( PRF ) therapy for low back pain relief compared with both electro-acupuncture ( EA ) therapy and the control group . But the functional improvement of the lumbar spine was proved under EA therapy only . Both therapies are related to electricity effects Previous studies reported that respiratory feedback ( RFB ) aids in alleviating chronic pain . However , to date , this adjunct treatment has not been rigorously tested against non-contingent ( placebo ) feedback . Forty-two patients with chronic low back pain were r and omized to either RFB or non-contingent RFB . Both groups performed a daily 30-min home training for 15 consecutive days . A respiratory associated relaxation index ( RI ) was measured . Pain levels and a somatosensory profile were assessed before and after intervention . Additionally , pain levels were assessed 3 months after the end of intervention . Secondary outcome parameters included daily functioning , psychopathology , and suggestibility . T-tests showed higher and significant pain reductions for RFB , compared to non-contingent RFB . Between-group comparisons reached no significance . However , changes were more pronounced in the RFB condition , which was also true for the course of the RI and the psychopathological scores . This is the first study using a non-contingent respiratory placebo feedback in a r and omized , controlled design . Within this design previous positive findings of symptom reductions in patients treated with RFB could partially replicated . Nonetheless , tendencies suggest that contingent feedback patients compared to placebo patients profit more from RFB in the long run regarding reduction of chronic pain and psychological distress STUDY OBJECTIVES To compare the efficacy of continuous radiofrequency ( CRF ) thermocoagulation with pulsed radiofrequency ( PRF ) in the treatment of lumbar facet syndrome . DESIGN Prospect i ve , r and omized , double-blinded study . SETTING Ambulatory pain clinic at a level-I trauma center and teaching institution . PATIENTS 50 ASA physical status I , II , and III patients , at least 18 years of age , scheduled to undergo CRF or PRF for lumbar back pain . INTERVENTIONS Target facet joints were identified with oblique radiographic views . Continuous radiofrequency thermocoagulation was delivered at 80 degrees C for 75 seconds , while PRF was delivered at 42 degrees C with a pulse duration of 20 ms and pulse rate of two Hz for 120 seconds . MEASUREMENTS Visual analog scale ( VAS ) pain assessment and Oswestry Low Back Pain and Disability Question naire ( OSW ) were administered at baseline and then at three months . Comparisons between groups and within groups were made of the relative percentage improvement in VAS and OSW scores . MAIN RESULTS No significant differences in the relative percentage improvement were noted between groups in either VAS ( P = 0.46 ) or OSW scores ( P = 0.35 ) . Within the PRF group , comparisons of the relative change over time for both VAS ( P = 0.21 ) and OSW scores ( P = 0.61 ) were not significant . However , within the CRF group , VAS ( P = 0.02 ) and OSW scores ( P = 0.03 ) showed significant improvement . CONCLUSIONS Although there was no significant difference between CRF and PRF therapy in long-term outcome in the treatment of lumbar facet syndrome , there was a greater improvement over time noted within the CRF group PURPOSE The objective of this placebo-controlled trial was to determine the efficacy and safety of carisoprodol ( Soma , MedPointe Pharmaceuticals , Somerset , NJ , USA ) , a central ly acting skeletal muscle relaxant used to treat acute , painful musculoskeletal conditions , at a dosage of 250 mg three times daily and at bedtime in patients with acute , painful muscle spasm of the lower back . METHODS This was a 7-day , multicenter , r and omized , double-blind , placebo-controlled , parallel-group study . Qualified patients were r and omly assigned to treatment with carisoprodol 250-mg tablets ( n = 277 ) or matching placebo tablets ( n = 285 ) . The co primary efficacy endpoints were patient-rated global impression of change and patient-rated relief from starting backache scored on a 5-point rating scale . The primary analysis was on study Day 3 . Four secondary endpoints were also assessed : ( 1 ) the Rol and -Morris Disability Question naire ( RMDQ ) , ( 2 ) time to symptom improvement , ( 3 ) patient-rated medication helpfulness , and ( 4 ) physician assessment of range of motion . RESULTS Carisoprodol was significantly more effective than placebo for patient-rated global impression of change ( 2.24 vs. 1.70 ; p < 0.0001 ) and patient-rated relief from starting backache ( 1.83 vs. 1.12 ; p < 0.0001 ) . Patients experienced clinical improvement with or without sedation . Onset of moderate or marked improvement was 3 days with carisoprodol compared to 6 days with placebo ( p < 0.0001 ) . No patient discontinued treatment with carisoprodol because of drowsiness , and there were no serious adverse events or clinical ly significant effects on laboratory values or vital signs . CONCLUSIONS In this study , patients with acute muscle spasm of the lower back had significantly greater and more rapid relief from starting backache , and had improved functional status , as measured by the RMDQ , during treatment with carisoprodol 250-mg tablets compared to placebo . Patients experienced clinical improvement with or without sedation Background : Low back pain is a common medical and social problem associated with disability and absence from work . Knowledge on effective return to work ( RTW ) interventions is scarce . Objective : To determine the effectiveness of grade d activity as part of a multistage RTW programme . Design : R and omised controlled trial . Setting : Occupational healthcare . Subjects : 112 workers absent from work for more than eight weeks due to low back pain were r and omised to either grade d activity ( n = 55 ) or usual care ( n = 57 ) . Intervention : Grade d activity , a physical exercise programme aim ed at RTW based on operant-conditioning behavioural principles . Main outcome measures : The number of days off work until first RTW for more then 28 days , total number of days on sick leave during follow up , functional status , and severity of pain . Follow up was 26 weeks . Results : Grade d activity prolonged RTW . Median time until RTW was equal to the total number of days on sick leave and was 139 ( IQR = 69 ) days in the grade d activity group and 111 ( IQR = 76 ) days in the usual care group ( hazard ratio = 0.52 , 95 % CI 0.32 to 0.86 ) . An interaction between a prior workplace intervention and grade d activity , together with a delay in the start of the grade d activity intervention , explained most of the delay in RTW ( hazard ratio = 0.86 , 95 % CI 0.40 to 1.84 without prior intervention and 0.39 , 95 % CI 0.19 to 0.81 with prior intervention ) . Grade d activity did not improve pain or functional status clinical ly significantly . Conclusions : Grade d activity was not effective for any of the outcome measures . Different interventions combined can lead to a delay in RTW . Delay in referral to grade d activity delays RTW . In implementing grade d activity special attention should be paid to the structure and process of care Objective The primary aim was to determine if laser acupuncture ( LA ) is more effective than sham laser in reducing pain and disability in adults with chronic non-specific low back pain . Methods The design was a double blind , two-group parallel r and omised controlled trial . The active intervention was an 830 nm ( infrared ) , 10 mW , Ga-Al-As laser diode laser for acupuncture and a sham control . The primary outcome measures were changes in pain ( visual analogue scale ) and disability ( Oswestry Disability Index ) at the end of 5–10 treatment sessions . Secondary outcomes were patient global assessment , psychological distress ( Depression Anxiety Stress Scale ) and subjective wellbeing ( Personal Wellbeing Index ) . Follow up was performed at 6 weeks and 6 months after completion of treatment . Results 100 participants were enrolled and treated in a general practice setting . Per protocol analysis of the primary outcome measures using ANOVA suggested that although there was a significant overall improvement in pain and disability after the course of treatments ( p<0.01 ) , there was no significant difference between the intervention and control group in both the primary and most secondary outcome measures . Conclusion This study did not show a specific effect for LA using infrared laser at 0.2 Joules per point for chronic low back pain . The overall intervention appeared effective because of placebo and other factors . As there was some concern about baseline ine quality between the groups further research using tighter inclusion criteria should attempt to replicate the result and examine if a dose response may exist OBJECTIVE To assess the cost-utility of an exercise programme vs usual care after functional multidisciplinary rehabilitation in patients with chronic low back pain . DESIGN Cost-utility analysis alongside a r and omized controlled trial . SUBJECTS/ PATIENTS A total of 105 patients with chronic low back pain . METHODS Chronic low back pain patients completing a 3-week functional multidisciplinary rehabilitation were r and omized to either a 3-month exercise programme ( n = 56 ) or usual care ( n = 49 ) . The exercise programme consisted of 24 training sessions during 12 weeks . At the end of functional multidisciplinary rehabilitation and at 1-year follow-up quality of life was measured with the SF-36 question naire , converted into utilities and transformed into quality --adjusted life years . Direct and indirect monthly costs were measured using cost diaries . The incremental cost-effectiveness ratio was calculated as the incremental cost of the exercise programme divided by the difference in quality -adjusted life years between both groups . RESULTS Quality of life improved significantly at 1-year follow-up in both groups . Similarly , both groups significantly reduced total monthly costs over time . No significant difference was observed between groups . The incremental cost-effectiveness ratio was 79,270 euros . CONCLUSION Adding an exercise programme after functional multidisciplinary rehabilitation compared with usual care does not offer significant long-term benefits in quality of life and direct and indirect costs Study Design . A cluster r and omized controlled trial and economic evaluation with a 12-month follow-up and with work department as the unit of r and omization . Objective . To evaluate the effectiveness of a prevention program for low back pain ( LBP ) in an occupational setting with an economic evaluation . Summary of Background Data . LBP accounts for high economic costs in Western societies . Little is known on the effectiveness and related costs and savings of prevention programs for LBP . Methods . The study population consisted of workers in physically dem and ing jobs from 9 large companies located throughout The Netherl and s. In each company , 2 comparable work units were r and omly allocated , result ing in 18 clusters with 258 workers assigned to the intervention group and 231 workers to the control group . Results . Results in our study did not show significant differences in effects or costs savings of the program . Indirect costs related to work absence and productivity losses accounted for the majority ( 84 % ) of total costs due to LBP . Conclusions . This study provides no evidence for the adoption of this worksite prevention program for LBP STUDY DESIGN A three and six months follow-up in a r and omized controlled trial . BACKGROUND Back School has become a widespread exercise program for low back pain ( LBP ) , since its introduction in 1969 . Back School could improve quality of life ( QoL ) , but there are controversial data regarding its effectiveness . AIM To evaluate the effects of the Back School program on quality of life ( primary outcome ) , disability and pain perceptions ( secondary outcomes ) in patients with chronic and non-specific low back pain . SETTING Rehabilitative specialized centre . POPULATION Seventy four patients with chronic non-specific LBP . METHODS Patients were r and omly placed in a 3:2 form and were allocated into 2 groups ( treated-control ) . Treatment group participated in a intensive multidisciplinary Back School program including brief education and active back exercises ( BSG , N.=41 ) , while the control group received medical assistance ( CG , N.=29 ) . Medication was the same in both groups . The Short Form 36 Health Status Survey , Waddel Index , Oswestry Disability Index and Visual Analogue Scale were collected at baseline , at the end of treatment , and at the three and six month follow-up . RESULTS Quality of life significantly improved along time more in BSG , both in Physical and Mental Composite Score ( repeated measure Anova : interaction time per group : P<0.001 and P=0.002 , respectively ) . We also observed a significant improvement in disability scores along time ( P<0.001 ) in BSG with significant differences between groups at three and at six months for Waddell Index ( P=0.006 and P=0.009 respectively ) and for Oswestry Disability Index ( P=0.018 and 0.011 respectively ) . Moreover , pain perception score VAS showed a reduction in both groups , but it was significantly lower in BSG at end of treatment and both follow-ups ( P<0.001 ) . CONCLUSION Our Back School program can be considered an effective treatment in people with chronıc non-specıfıc LBP Study Design . The study was a r and omized controlled trial . Treatment was for 8 weeks , with follow-up posttreatment and at 6- , 12- , and 36- months . Objective . The purpose was to evaluate the effect of a grade d exercise intervention emphasizing stabilizing exercises in patients with nonspecific , recurrent low back pain ( LBP ) . Summary of Background Data . Exercise therapy is recommended and widely used as treatment for LBP . Although stabilizing exercises are reportedly effective in the management of certain subgroups of LBP , such intervention protocol s have not yet been evaluated in relation to a more general exercise regimen in patients with recurrent LBP , all at work . Methods . Seventy-one patients recruited consecutively ( 36 men , 35 women ) with recurrent nonspecific LBP seeking care at an outpatient physiotherapy clinic were r and omized into 2 treatment groups ; grade d exercise intervention or daily walks . The primary outcome was perceived disability and pain at 12-month follow-up . Secondary outcomes included physical health , fear-avoidance , and self-efficacy beliefs . Results . Of the participants , 83 % provided data at the 12-month follow-up and 79 % at 36 months . At 12 months , between-group comparison showed a reduction in perceived disability in favor of the exercise group , whereas such an effect for pain emerged only immediately postintervention . Ratings of physical health and self-efficacy beliefs also improved in the exercise group over the long term , though no changes were observed for fear-avoidance beliefs . Conclusion . A grade d exercise intervention , emphasizing stabilizing exercises , for patients with recurrent LBP still at work seems more effective in improving disability and health parameters than daily walks do . However , no such positive results emerged for improvement regarding pain over a longer term , or for fear-avoidance beliefs Study Design . A r and omized controlled study investigated the effects of therapeutic climbing in patients with chronic low back pain . Before and after 4 weeks of training , physical and mental well-being were measured by two question naires ( 36-Item Short Form Health Survey [ SF-36 ] ; Hannover Functional Ability Question naire for measuring back pain – related disability [ FFbH-R ] ) . Objective . Therapeutic climbing has been suggested to increase muscular strength and perceived physical and mental well-being . This study focused on the psychological effects of therapeutic climbing and compared it with st and ard exercise therapy . Summary of Background Data . Therapeutic climbing has become increasingly popular in rehabilitation and its effects on muscular strengthening have been shown . Therapeutic climbing has also been suggested to yield psychological effects such as changes in attentional focus from pain to physical capabilities . To date , no controlled clinical trial has investigated these psychological effects and it is unclear whether therapeutic climbing is comparable or superior to other forms of exercise . Methods . Twenty-eight patients with chronic low back pain conducted either a therapeutic climbing or a st and ard exercise regime . Each program took 4 weeks , including four guided training sessions per week . Before and after the program , patients answered two question naires assessing their physical and mental well-being . Results . For the Hannover Functional Ability Question naire for measuring back pain – related disability , there was no difference before versus after or between the treatments . For the SF-36 , both treatments showed significant improvements in 3/8 subscales of the SF-36 . In 2/8 subscales , only the participants of the therapeutic climbing improved and in 1/8 subscales the converse was true . Comparing both groups , significantly larger improvements were found after therapeutic climbing in two subscales of the SF-36 : physical functioning and general health perception . Conclusion . The benefits of therapeutic climbing were comparable with those of a st and ard exercise regime . In two subscales of the SF-36 , the benefits of therapeutic climbing exceeded those of st and ard exercise therapy , primarily in perceived health and physical functioning of the patients . This finding demonstrates that therapeutic climbing is equivalent and partly superior to st and ard exercise therapy for patients with chronic low back pain Study Design . Prospect i ve , r and omized , controlled trial . Objective . To investigate the effectiveness of home-based exercise on pain , dysfunction , and quality of life ( QOL ) in Japanese individuals with chronic low back pain ( CLBP ) . Summary of Background Data . Exercise therapy is a widely used treatment for CLBP in many countries . The studies on its effectiveness have been performed only in Western industrialized countries . The existence of cross-cultural differences and heterogeneity of patients in each country may influence the outcome of interventions for CLBP . Data that would enable research ers to compare the effectiveness of interventions between widely different societies is lacking . Methods . A total of 201 patients with nonspecific CLBP were r and omly assigned to either the control or exercise therapy group : 89 men and 112 women with a mean age of 42.2 years . The control group was treated with nonsteroidal anti-inflammatory drugs ( NSAIDs ) , and the exercise group performed trunk muscle strengthening and stretching exercises . The primary outcome measures were pain intensity ( visual analogue scale ) and dysfunction level ( Japan Low back pain Evaluation Question naire [ JLEQ ] and Rol and -Morris Disability Question naire [ RDQ ] ) over 12 months . The secondary outcome measure was FFD ( Finger-floor distance ) . Statistical analysis was performed using Wilcoxon signed-ranks and Mann-Whitney U tests , and estimation of the median with 95 % CI was calculated . Results . In both groups , significant improvement was found at all points of follow-up assessment . However , JLEQ and RDQ were significantly more improved in the exercise group compared to the control group ( P = 0.021 in JLEQ , P = 0.023 in RDQ ) . The 95 % CI for the difference of medians of the change ratio between exercise and NSAID groups , [ Exercise ] − [ NSAID ] , was −0.25 to −0.02 in JLEQ , −0.33 to 0.00 in RDQ , and −0.20 to 0.06 in visual analogue scale . Conclusion . The home-based exercise prescribed and monitored by board-certified orthopedic surgeons was more effective than NSAIDs for Japanese patients with CLBP Objective : To compare spinal manipulation , back school and individual physiotherapy in the treatment of chronic low back pain . Design : R and omized trial , 12-month follow-up . Setting : Outpatient rehabilitation department . Participants : 210 patients with chronic , non-specific low back pain , 140/210 women , age 59 ± 14 years . Interventions : Back school and individual physiotherapy scheduled 15 1-hour-sessions for 3 weeks . Back school included : group exercise , education/ ergonomics ; individual physiotherapy : exercise , passive mobilization and soft-tissue treatment . Spinal manipulation , given according to Manual Medicine , scheduled 4 to 6 20’-sessions once-a-week . Outcome : Rol and Morris Disability Question naire ( scoring 0 - 24 ) and Pain Rating Scale ( scoring 0 - 6 ) were assessed at baseline , discharge 3 , 6 , and 12 months . Results : 205 patients completed the study . At discharge , disability score decreased by 3.7 ± 4.1 for back school , 4.4 ± 3.7 for individual physiotherapy , 6.7 ± 3.9 for manipulation ; pain score reduction was 0.9 ± 1.1 , 1.1 ± 1.0 , 1.0 ± 1.1 , respectively . At 12 months , disability score reduction was 4.2 ± 4.8 for back school , 4.0 ± 5.1 for individual physiotherapy , 5.9 ± 4.6 for manipulation ; pain score reduction was 0.7 ± 1.2 , 0.4 ± 1.3 , and 1.5 ± 1.1 , respectively . Spinal manipulation was associated with higher functional improvement and long-term pain relief than back school or individual physiotherapy , but received more further treatment at follow-ups ( P<0.001 ) ; pain recurrences and drug intake were also reduced compared to back school ( P < 0.05 ) or individual physiotherapy ( P < 0.001 ) . Conclusions : Spinal manipulation provided better short and long-term functional improvement , and more pain relief in the follow-up than either back school or individual physiotherapy OBJECTIVES This study explored how the effectiveness of prescription exercises for a home program for patients with non-specific low back pain by using the method with specified describing style in accordance with ATLAS ( The Assessing the Learning Strategies of Adults ) and traditional method that we often use in clinic . PATIENTS AND METHODS Twenty-six patients with non-specific low-back pain were referred to the physical therapy department for exercise therapy . Subjects were r and omly assigned to control group , and experimental group . The stability exercise procedures were considered for each group . For patients in control group , exercises procedures were demonstrated with wording that we often use in clinic . For patients in experimental group , it was done by using the method with specified describing style in accordance with ATLAS ( The Assessing the Learning Strategies of Adults ) . An Exercise Assessment Scale was also developed to measure exercise performance for this study . RESULTS All demographic parameters , functionality scores , and distribution of learning strategies were homogeneous in two groups . The correlation tests showed no significant relationship between personal factors and properly perception of the home exercise program in control and experimental group . Exercise Assessment Scale scores were compared in both groups which showed a significantly superiority in experimental group compared to the control group . CONCLUSIONS The wording that we often use in clinic to describe home exercise program in patients with non-specific low back pain is not sufficient . While the method of specified describing style in accordance with ATLAS is more effective in underst and ing of exercises Study Design . R and omized Clinical Trial . Objective . To identify a subgroup of patients with low back pain who are likely to respond favorably to an intervention including mechanical traction . Summary of Background Data . Previous research has failed to find evidence supporting traction for patients with low back pain . Previous studies have used heterogeneous sample s , although clinical experts tend to recommend traction for a more limited subgroup of patients with low back pain . Methods . Sixty-four subjects ( mean age 41.1 year , 56.3 % female ) with low back and leg pain and signs of nerve root compression were r and omized to receive a 6-week extension-oriented intervention with or without mechanical traction during the first 2 weeks . Between-group comparisons were conducted for changes in pain , disability , and fear-avoidance beliefs . Baseline variables were explored for potential as subgrouping criteria defining a subgroup of subjects likely to benefit from traction . Results . The group receiving traction showed greater improvements in disability ( adjusted mean difference in Oswestry change 7.2 points ) and fear-avoidance beliefs ( adjusted mean difference in FABQPA change 2.6 points ) after 2 weeks . There were no between-group differences after 6 weeks . Two baseline variables were associated with greater improvements with traction treatment ; peripheralization with extension movements and a crossed straight leg raise . Conclusion . A subgroup of patients likely to benefit from mechanical traction may exist . The results of this study suggest this subgroup is characterized by the presence of leg symptoms , signs of nerve root compression , and either peripheralization with extension movements or a crossed straight leg raise . Further research is needed to vali date this finding OBJECTIVE This study assessed the potential effects of age , sex , and prior opioid use on the response to oxymorphone extended release ( ER ) in patients with moderate to severe chronic low back pain . METHODS Combined data from 2 placebo-controlled clinical trials with an enriched-enrollment , r and omized-withdrawal design were analyzed . In patients aged > or = 18 years with chronic low back pain , the dose of oxymorphone ER was titrated to a stable , tolerable , effective dose . Patients who completed titration were r and omly assigned to a 12-week double-blind study period with oxymorphone ER or placebo . Oxymorphone immediate release 5 mg was permitted q4 - 6h , as needed for rescue medication or withdrawal symptoms , for 4 days after r and omization and restricted to 10 mg/d thereafter . Pain intensity ( 100-mm visual analog scale [ VAS ] ; 0 = no pain to 100 = worst pain imaginable ) and time to study discontinuation due to lack of efficacy were compared with stratification by age ( < 65 vs > or = 65 years ) , sex , and prior opioid use . Adverse events were categorized by severity and relation to study medication . RESULTS Of 575 patients , 348 completed titration and 347 entered the double-blind study phase . There were no significant between-group differences in demographic variables , except that the mean age in the oxymorphone ER group was significantly higher ( P = 0.04 ) , and the proportion of men was significantly lower ( P = 0.01 ) . There was no significant age difference between the oxymorphone ER and placebo groups stratified by age ( < 65 vs > or = 65 years ) . Fewer patients aged > or = 65 years versus < 65 years completed titration ( 45.0 % [ 36/80 ] vs 63.0 % [ 312/495 ] ; P = 0.002 ) . The least-squares mean ( SEM ) differences in VAS pain scores between the oxymorphone ER ( n = 174 ) and placebo ( n = 169 ) groups were significant at each postbaseline assessment ( P < 0.001 ) and at study completion ( 12.3 [ 2.8 ] mm ; P < 0.001 ) and was not significantly affected by age , sex , or prior opioid use . Age and sex had no significant influence on adverse events or discontinuations due to lack of efficacy . More discontinuations due to lack of efficacy occurred among patients in the placebo group ( hazard ratio , 5.01 ; P < 0.001 ) and among opioid-experienced patients . The latter effect was limited to opioid-experienced patients who received placebo . The rates of discontinuation due to lack of efficacy were similar between oxymorphone ER-treated opioid-naive and opioid-experienced patients ( 11.4 % vs 11.6 % ) . The proportion of patients who experienced opioid-related adverse events was significantly greater in the oxymorphone ER group compared with the placebo group ( 25.7 % vs 16.3 % ; P = 0.03 ) . The most frequent treatment-emergent adverse events in the oxymorphone ER group were nausea ( 8.0 % ) , constipation ( 6.3 % ) , vomiting ( 4.6 % ) , and diarrhea ( 4.0 % ) ; in the placebo group were nausea ( 5.8 % ) , diarrhea ( 4.7 % ) , and increased sweating ( 2.3 % ) . CONCLUSION In the enriched population of patients who successfully titrated to oxymorphone ER , oxymorphone ER was effective and generally well tolerated , independent of patients ' age , sex , or previous opioid use Study Design . Economic evaluation alongside a pragmatic multicenter r and omized controlled trial from the National Health Service ( NHS ) and societal perspective . Objective . To perform a cost-utility analysis of routine physiotherapy treatment compared with an assessment session and advice from a physiotherapist for patients with subacute and chronic low back pain . Summary of Background Data . Lack of evidence for some types of physiotherapy intervention and a paucity of cost-effectiveness data for treatment of low back pain has led to controversy and uncertainty within the medical and allied professions . Patients and Methods . A total of 286 patients with low back pain of more than a 6-week duration were r and omized to physiotherapy treatment or advice on remaining active from a physiotherapist . Data were collected on back pain-related NHS and patients ’ costs over a 12-month post r and omization period . The primary outcome measure was the Oswestry Disability Index at 12 months , with additional Oswestry Disability Index measures at 2 and 6 months . The EuroQol EQ-5D was used to calculate quality adjusted life years . Cost-effectiveness was expressed as the incremental cost per quality adjusted life year gained . Uncertainty was h and led using confidence ellipses for the ratio and cost-effectiveness acceptability curves . Results . The total NHS costs were not significantly different at £ 179 ( £ 221 ) for physiotherapy and £ 159 ( £ 260 ) for the advice group . However , patients in the physiotherapy group had significantly higher out-of-pocket health care expenditure ( £ 40 , 95 % confidence interval £ 9 to £ 71 ) . Utility levels improved in both groups from baseline to 12 months , with no significant differences between groups . Conclusions . The results indicate no significant differences in either NHS costs or effects . However , the significantly higher out-of-pocket expenses incurred by patients receiving routine physiotherapy suggests that advice given by a physiotherapist should be considered as the first-line treatment for patients with this level of back pain disability Objectives Owing to a lack of a suitable needle procedure , it has been impossible to evaluate the efficacy of acupuncture in clinical studies using double-blind testing . We evaluated the applicability of a new kind of press needle ( Pyonex ) to a double-blind trial by comparing the press needle with a placebo ( lacking the needle element ) . Methods The purpose of the study consisted of 2 phases . In the phase 1 , to evaluate the applicability and efficacy of the press needles , 90 participants who had never been treated using acupuncture were r and omly assigned to receive either the press needle ( n=45 ) or a placebo ( n=45 ) . The applicability was measured using a question naire regarding the perception of penetration , and efficacy was measured using a visual analog scale of low back pain ( LBP ) . When the applicability and efficacy of the press needles were confirmed in phase 1 , the mechanism of LBP relief by the press needles was examined in phase 2 . Results In phase 1 , intergroup comparisons showed no significant differences concerning the perception of penetration . In addition , for patients with LBP , the press needles reduced the subjective evaluation of LBP compared with the placebo ( P<0.05 ) . In phase 2 , visual analog scale results indicated that LBP was reduced significantly more in the press needle group than in the local anesthesia group ( P<0.05 ) . Discussion The participants could not distinguish between the press needle and a placebo , and the data from the press needle group suggested a specific influence on patients with LBP . These findings imply that the press needle and a placebo provide an effective means of realizing a double-blind setting for clinical studies of acupuncture OBJECTIVE To determine whether military health care beneficiaries with low back pain ( LBP ) who are likely to respond successfully to spinal manipulation experience a difference in short-term clinical outcomes based on the manipulation technique that is used . METHODS Sixty patients with LBP identified as likely responders to manipulation underwent a st and ardized clinical examination and were r and omized to receive a lumbopelvic ( LP ) or lumbar neutral gap ( NG ) manipulation technique . Outcome measures were a numeric pain rating scale and the modified Oswestry Disability Question naire . RESULTS Both the LP and NG groups experienced statistically significant reductions in pain and disability at 48 hours postmanipulation . The improvements seen in each group were small because of the short follow-up . There were no statistically significant or clinical ly meaningful differences in pain or disability between the two groups . CONCLUSION The two manipulation techniques used in this study were equally effective at reducing pain and disability when compared at 48 hours posttreatment . Clinicians may employ either technique for the treatment of LBP and can expect similar outcomes in those who satisfy the clinical prediction rule ( CPR ) . Further research is required to determine whether differences exist at longer-term follow-up periods , after multiple treatment sessions , or in different clinical population OBJECTIVE To assess the efficacy and treatment compliance of a home-based rehabilitation programme for chronic low back pain ( CLBP ) . POPULATION CLBP out patients treated in a Physical Medicine Rehabilitation or Rheumatology unit within a university hospital . METHODS We performed a prospect i ve , comparative study . The participants were r and omly assigned to either a home-based rehabilitation programme ( Gp A ) or a st and ard physical therapy ( Gp B ) . The programme included four weekly sessions . In each group , we measured pain intensity ( on a visual analogue scale , VAS ) , flexibility and muscle endurance ( the Schöber MacRae test , finger-to-floor distance , thigh-leg angle , the Shirado and Sorensen test ) , functional and psychological repercussions ( the Quebec functional index and the Hospital Anxiety and Depression scale ) and h and icap ( on a VAS ) . Follow-up examinations took place at baseline and four weeks and three , six and 12 months later . RESULTS One hundred and seven patients ( 82 women ) with a mean+/-st and ard deviation ( S.D. ) age of 35.7+/-0.8 years were included ( with 54 patients in Gp A ) . At four weeks , a significant improvement ( relative to baseline ) was observed for all parameters in both study groups but with a significantly greater difference in Gp A , which was maintained at one year ( despite an observed regression of the improvement at six months ) . At one year , compliance with the home-based rehabilitation programme was good ( 68.1 % ) and 59.5 % of the patients regarded the programme as useful . CONCLUSION Our results suggest that a home-based rehabilitation programme is as effective as st and ard physical therapy . However , this type of programme requires patient motivation and regular follow-up OBJECTIVE This study evaluated the effects of spinal manipulation on spatiotemporal flexion-relaxation phenomenon parameters in individuals with chronic low back pain . METHODS Twenty-seven adults with chronic low back pain participated in this study and first performed a block of 5 complete trunk flexion-extensions . The experimental group ( n = 13 ) was then su bmi tted to lumbar spine manipulation , whereas the control group ( n = 14 ) was placed in a side-lying control position for 10 seconds . All study participants performed thereafter a second block of 5 trunk flexion-extensions . Trunk and pelvis angles and surface EMG of erector spinae at L2 and L5 were recorded during the flexion-extension tasks . Flexion angles corresponding to the onset and cessation of myoelectric silence , normalized EMG , and the extension-relaxation ratio were compared across experimental conditions . RESULTS A significant reduction of EMG activity at full trunk flexion at the L2 erector spinae level was observed in the experimental group compared to the control group . No significant effect was seen at L5 in both groups . The experimental group presented a significantly increased postmanipulation FRR at L2 , whereas the control group ratio did not vary after the " side-lying control position . " No significant difference was seen at L5 in both groups . Flexion-relaxation phenomenon onset and cessation angle did not differ across groups or conditions . CONCLUSIONS This study shows that lumbar spine manipulation can , at least for a brief period , modulate stabilizing neuromuscular responses of the lumbar spine in a group of patients with low back pain BACKGROUND Low back pain ( LBP ) is a common musculoskeletal disorder that is highly prevalent in the general population . Management of this pathology includes numerous interventions depending on pain severity : analgesic , nonsteroidal anti-inflammatory drugs , steroid injections . However , the effect size and duration of symptom relief are limited . Physical therapy ( ultrasound [ US ] , laser therapy , manual therapy , interferential current therapy , Back School , aerobic work , therapeutic aquatic exercise acupuncture ) have been reported often with mixed results . AIM To evaluate the short-term effectiveness of high-intensity laser therapy ( HILT ) versus ultrasound ( US ) therapy in the treatment of LBP . DESIGN R and omized clinical trial . SETTING University hospital . POPULATION Thirty patients with LBP were r and omly assigned to a HILT group or a US therapy group . METHODS Study participants received fifteen treatment sessions of HILT or US therapy over a period of three consecutive weeks ( five days/week ) . RESULTS For the 30 study participants there were no between-group differences at baseline in Visual Analogic Scale ( VAS ) and Oswestry Low Back Pain Disability Question naire ( OLBPDQ ) scores . At the end of the 3-week intervention , participants in the HILT group showed a significantly greater decrease in pain ( measured by the VAS ) and an improvement of related disability ( measured by the OLBPDQ ) compared with the group treated with US therapy . CONCLUSION Our findings obtained after 15 treatment sessions with the experimental protocol suggested greater effectiveness of HILT than of US therapy in the treatment of LBP , proposing HILT as a promising new therapeutic option into the rehabilitation of LBP Objective : To investigate the effects of high-intensity aerobic exercise on adrenocortical responsiveness and on st and ard outcome measures in patients with chronic low back pain . Design : Controlled clinical trial . Setting : Physical therapy department of a university general hospital . Subjects : Sixty-four patients with chronic low back pain were r and omly allocated into positive and negative suppression test groups and assigned to exercise protocol . Interventions : Subjects in the positive and negative dexamethasone suppression test groups received a 12-week high-intensity aerobic exercise programme . Main outcome measures : Dexamethasone suppression test as an index of adrenocortical responsiveness , pain measured with the McGill Pain Question naire , functional status measured with the Rol and Morris Disability Question naire , and psychological strain measured with the Hospital Anxiety and Depression Scale . Results : Data analysis in the positive group identified a significant reduction of pain by 30 % ( t 30 = 11.2 , P<0.001 ) , a recovery of the lost functioning by 34 % ( t 30 = 19.7 , P<0.001 ) , a reduction of anxiety/depression by 25 % ( t 30 = 10.2 , P<0.001 ) , and a change in adrenocortical responsiveness by 40 % ( t30 = 14.1 , P<0.001 ) . In the dexamethasone suppression test negative group , data analysis identified a significant reduction of pain by 8 % ( t31 = 4.2 , P<0.001 ) , a recovery of lost functioning by 10 % ( t31 = 4.8 , P<0.001 ) , a reduction of anxiety/depression by 11 % ( t31 = 5.0 , P<0.001 ) , and no change in adrenocortical responsiveness ( t31 = 1.2 , P=0.22 ) . In univariate analysis between-subject differences were significant for dexamethasone suppression test ( F61 = 163 , P<0.001 ) , and for anxiety/depression ( F61 = 21.3 , P<0.001 ) . Conclusion : Exercise alleviated pain , functional disability and anxiety/depression , also improved adrenocortical responsiveness in patients with chronic low back pain with dexamethasone suppression test positive values Objective This r and omized clinical trial examined the efficacies of a group-based multidisciplinary rehabilitation program and oral drug treatment versus oral drug treatment alone in Iran . Methods A total of 197 patients with chronic low back pain were r and omized to either intervention group ( n=97 ) receiving a group-based , 5-session multidisciplinary rehabilitation program plus oral medication or to control group ( n=100 ) receiving just oral medication . At baseline and at 3 and 6-month follow-ups , patients filled out question naires on health-related quality of life ( 36-item Short-form General Health Survey ) and disability Question naires ( Quebec Disability Scale and Ronald-Morris Disability ) . Repeated measure analysis of variance was used to compare 2 groups during time . Results The 2 groups were comparable regarding all baseline characteristics ( P>0.05 ) . There were significant differences within each group by time in terms of all subscales of 36-item Short-form ( P<0.01 ) except for mental health ( P=0.7 ) . Furthermore , there were significant deferences between groups in terms of all domains of SF-36 scale except for general health ( P=0.06 ) , social function ( P=0.08 ) and role emotional ( P=0.7 ) . Furthermore , according to the scores of Ronald-Morris Disability Question naire and Quebec Disability Scale , the disability of patients in the intervention group was improved over time significantly ( P=0.01 and P<0.0001 , respectively ) . Discussion The findings revealed that the group-based multidisciplinary program could improve most domains of quality of life in chronic low back pain patients in the 6-month period . However , there were no significant differences between two groups in sub scales such as general health , social function and role emotional Introduction In an earlier study , Gatchel et al. ( J Occup Rehabil 13:1–9 , 2003 ) demonstrated that participants at high risk for developing chronic low back pain disability ( CLBPD ) , who received a biopsychosocial early intervention treatment program , displayed significantly more symptom improvement , as well as cost savings , relative to participants receiving st and ard care . The purpose of the present study was to exp and on these results by examining whether the addition of a work-transition component would further strengthen the effectiveness of this early intervention treatment . Methods Using an existing algorithm , participants were identified as being high-risk ( HR ) or low-risk ( LR ) for developing CLBPD . HR participants were then r and omly assigned to one of three groups : early intervention ( EI ) ; early intervention with work transition ( EI/WT ) ; or st and ard care ( SC ) . Participants provided information regarding pain , disability , work status , and psychosocial functioning at baseline , periodically during treatment , and again 1 year following completion of treatment . Results At 1-year follow-up , no significant differences were found between the EI and EI/WT groups in terms of occupational status , self-reports of pain and disability , coping ability or psychosocial functioning . However , significant differences in all these outcomes were found comparing these groups to st and ard care . Conclusion The addition of a work transition component to an early intervention program for the treatment of ALBP did not significantly contribute to improved work outcomes . However , results further support the effectiveness of early intervention for high-risk ALBP patients Study Design . Cluster r and omized controlled trial . Objective . To improve quality of care for patients with low back pain ( LBP ) a multifaceted general practitioner education alone and in combination with motivational counseling by practice nurses has been implemented in German general practice s. We studied effects on functional capacity ( main outcome ) , days in pain , physical activity , quality of life , or days of sick leave ( secondary outcomes ) compared with no intervention . Summary of Background Data . International research has lead to the development of the German LBP guideline for general practitioners . However , there is still doubt about the most effective implementation strategy . Although effects on process of care have been observed frequently , changes in patient outcomes are rarely seen . Methods . We recruited 1378 patients with LBP in 118 general practice s , which were r and omized to 1 of 3 study arms : a multifaceted guideline implementation ( GI ) , GI plus training of practice nurses in motivational counseling ( MC ) , and the postal dissemination of the guideline ( controls , C ) . Data were collected ( question naires and patient interviews ) at baseline and after 6 and 12 months . Multilevel mixed effects modeling was used to adjust for clustering of data and potential confounders . Results . After 6 months , functional capacity was higher in the intervention groups with a cluster adjusted mean difference of 3.650 between the MC group and controls ( 95 % CI = 0.320–6.979 , P = 0.032 ) and 2.652 between the GI group and controls ( 95 % CI = −0.704 to 6.007 , P = 0.120 ) . Intervention effects were more pronounced regarding days in pain per year with an average reduction of 16 ( GI ) to 17 days ( MC ) after 6 months ( 12 and 9 days after 12 months ) compared with controls . Conclusion . Active implementation of the German LBP guideline results in slightly better outcomes during 6 months follow-up than its postal dissemination . Results are more distinct when practice nurses are trained in motivational counseling Objective : To evaluate the cost-effectiveness and cost-utility of a return to work ( RTW ) program for workers on sick-leave due to low back pain ( LBP ) , comparing a workplace intervention implemented between 2 to 8 weeks of sick-leave with usual care , and a clinical intervention after 8 weeks of sick-leave with usual care . Design : Economic evaluation alongside a r and omised controlled trial ( RCT ) . Study population : Workers sick-listed for a period of 2 to 6 weeks due to LBP . Interventions : 1 . workplace assessment , work modifications and case management ) . 2 . physiotherapy based on operant behavioural principles . 3 . usual care : provided by an occupational physician . Outcomes : The primary outcome was return to work ( RTW ) . Other outcomes were pain intensity , functional status , quality of life and general health . The economic evaluation was conducted from a societal perspective . Outcomes were assessed at baseline ( after 2–6 weeks on sick-leave ) , and 12 weeks , 26 weeks , and 52 weeks after the first day of sick-leave . Results : The workplace intervention group returned to work 30.0 days ( 95 % CI=[3.1 , 51.3 ] ) earlier on average than the usual care group at slightly higher direct costs ( ratio of 1 day : € 19 ) . Workers in the clinical intervention group that had received usual care in the first 8 weeks returned to work 21.3 days ( 95 % CI= [ −74.1 , 29.2 ] ) later on average . The group that had received the workplace intervention in the first 8 weeks and the clinical intervention after 8 weeks returned to work 50.9 days ( 95 % CI=[−89.4 , −2.7 ] ) later on average . A workplace intervention was more effective than usual care in RTW at slightly higher costs and was equally effective as usual care at equal costs on other outcomes . A clinical intervention was less effective than usual care and associated with higher costs . Conclusion : The workplace intervention results in a safe and faster RTW than usual care at reasonable costs for workers on sick-leave for two to six weeks due to LBP OBJECTIVE To evaluate the effectiveness of a topical local anesthetic cream ( 5 % liposomal lidocaine ) in reducing needle-induced pain in patients investigated for suspected zygapophysial ( z-joint ) or sacroiliac ( SI ) joint pain . DESIGN Triple-blinded r and omized controlled trial . Setting . Interventional fluoroscopy suite . STUDY POPULATION Eighteen patients presenting with chronic mechanical low back pain . INTERVENTIONS Thirty minutes prior to diagnostic z- or SI joint blocks , equivalent amounts of topical 5 % liposomal lidocaine cream was applied to one side of the low back and a placebo cream to the other . The treatment side and injection order were r and omized and the patient , injectionist , and data recorder were blinded . OUTCOME MEASURES The subjects provided numerical rating scores of pain intensity immediately following each phase of the injection ( skin penetration , deep , overall ) . Scores were analyzed with dependent t-tests . RESULTS The injection associated pain was significantly less during the skin penetration phase on the side of the local anesthetic vs the placebo cream ( 3.0/10 vs 4.2/10 ; P = 0.002 ) . No significant differences were found during the deep phase or for the injection procedure overall . CONCLUSIONS Five percent liposomal lidocaine cream significantly reduces the pain associated with the skin penetration phase of lumbosacral diagnostic blocks but does not change the pain associated with the deep phase or the injection procedure overall . Its usefulness for this application is question able ABSTRACT Objective : Determine the efficacy and tolerability of oxymorphone extended release ( OPANA ER† ) in opioid-naive patients with moderate to severe chronic low back pain ( CLBP ) . Design and methods : Patients ≥ 18 years of age were titrated with oxymorphone ER ( 5- to 10‑mg increments every 12 h , every 3–7 days ) to a well-tolerated , stabilized dose . Patients were then r and omized to continue their oxymorphone ER dose or receive placebo every 12 h for 12 weeks . Oxymorphone immediate release was available every 4–6 h , as needed , for the first 4 days and twice daily thereafter . Results : Sixty-three percent of patients ( 205/325 ) were titrated to a stabilized dose of oxymorphone ER , most ( 203/205 ) within 1 month . During titration , 18 % discontinued from adverse events ( AEs ) and 1 % from lack of efficacy . For patients completing titration , average pain intensity decreased from 69.4 mm at screening to 22.7 mm ( p < 0.0001 ) . After r and omization , 68 % of oxymorphone ER and 47 % of placebo patients completed 12 weeks of double-blind treatment . Approximately 8 % of patients in each group discontinued because of AEs . Placebo patients discontinued significantly sooner from lack of efficacy than those receiving oxymorphone ER ( p < 0.0001 ) . Pain intensity increased significantly more in the placebo group ( least squares [ LS ] mean change 26.9 ± 2.4 [ median 28.0 ] ) than in the oxymorphone ER group ( LS mean change 10.0 ± 2.4 [ median 2.0 ] ; p < 0.0001 ) . Oxymorphone ER was generally well tolerated without unexpected AEs . Although limitations of a r and omized withdrawal study include the potential for unblinding and opioid withdrawal in placebo patients , opioid withdrawal was limited to two patients in the placebo group and one in the oxymorphone ER group . Conclusions : Stabilized doses of oxymorphone ER were generally safe and effective over a 12‑week double-blind treatment period in opioid-naive patients with CLBP The objectives of this study were to compare the effects of three different Pilates regimes on chronic , mild low back pain symptoms and to determine whether the efficiency of load transfer through the pelvis is improved by those exercises . A between subjects equivalent group experimental design was used . The independent variable was the type of exercise training ( three groups ) and the two-dependent variables were low back pain symptoms and load transfer through the pelvis . The outcome measures of the first-dependent variable were a comparison between modified Oswestry Disability Question naires ( one of the st and ard pain instruments ) completed pre- and post-program and frequency , intensity and duration of low back pain . The outcome measure of the second-dependent variable , efficiency of load transfer through the pelvis was the Stork test ( one-legged st and ing test ) in weight bearing . Although all groups experienced statistically significant reductions in frequency , intensity and duration of low back pain across the weeks of exercising , there were no significant differences between the groups relative to each other OBJECTIVE The aim of this study was to evaluate the effectiveness of thermal mineral water , compared with tap water in the treatment of low back pain . METHODS This r and omized , double-blind , controlled , follow-up study included 71 patients who underwent 20-minute daily treatment sessions with medicinal water or with tap water , both at a temperature of 34 degrees C , on 21 occasions . Both groups underwent additional adjunctive electrotherapy . Outcome measures were visual analogue scale scores , Schober 's sign , Domján 's signs , Oswestry disability and Short Form-36 question naire . The study parameters were administered at baseline , immediately after treatment , and after 15 weeks . RESULTS After treatment , there was a significant improvement in all parameters in the thermal water group . This improvement was still evident after 15 weeks . The improvement in the control group was less substantial compared with baseline values . Comparison of the 2 treatments revealed a statistically significant difference in 3 outcome parameters ( visual analogue scale scores III , IV and Schober 's index ) . In the subset of patients who completed the study according to the protocol , the greater efficacy of treatment with thermal water was also confirmed by the other study parameters . CONCLUSION In the group treated with thermal water , improvement occurred earlier , lasted longer and was statistically significant A prospect i ve experimental study on 97 patients of chronic low back pain was conducted to find out the effects of shortwave diathermy . They were divided r and omly into two groups and treated with nonsteroidal anti-inflammatory drugs , exercises , activities of daily living instructions and with or without shortwave diathermy . After six weeks of treatment , improvements were observed in both the groups . But significant difference in improvement was found in shortwave diathermy group than in placebo group . The present study suggests that shortwave diathermy is effective for the treatment of patients with chronic low back pain Abstract A large number of prognostic factors have been associated with recovery from an episode of back pain , and much emphasis has been placed on psychosocial prognostic factors . The large number of prognostic factors and the lack of comparative analysis of different factors make use of these difficult in clinical practice . The aim of this study was to evaluate the comparative usefulness of a range of factors to predict outcome using data from a r and omized controlled trial ( RCT ) in which 312 patients with sub-acute to chronic back pain received a mechanical evaluation and were sub-grouped based on the presence or absence of directional preference ( DP ) . Patients were then r and omized to treatment that was matched or unmatched to that DP . Patients with a minimal reduction of 30 % in Rol and -Morris Disability Question naire ( RMDQ ) score were defined as the good outcome group . Seventeen baseline variables were entered into a step-wise logistic regression analysis for the ability to predict a good outcome . Of the patients , 84 met the good outcome criteria and had a mean RMDQ decrease of 58.2 % ( 9.8 points ) in 4 visits . Leg pain , work status , depression , pain location , chronicity , and treatment assignment were significant predictors of outcome in univariate analysis . Only leg bothersomeness rating and treatment assignment survived multivariate analysis . Subjects with DP/ central ization who received matched treatment had a 7.8 times greater likelihood of a good outcome . Matching patients to their DP is a stronger predictor of outcome than a range of other biopsychosocial factors AIM Progressive resistance exercises ( PRE ) are prescribed to reverse the deconditioning associated with chronic back pain . The spine rehabilitation program has utilized 2 sets of progressive resistance exercises during each session , with increased resistance between sets , and with successive sessions . Exercise literature has challenged the need for multiple sets of resistance exercises , with a single set producing similar functional benefits . The authors studied whether completing 1 versus 2 sets of resistance exercises would affect strength , pain and disability outcomes in subjects with chronic low back pain ( CLBP ) . METHODS The study r and omly assigned subjects with CLBP to perform either 1 set or 2 sets of progressive resistance exercises during otherwise identical spine rehabilitation programs . The patient sample included 100 subjects ( 36 male patients , 64 female patients , mean age 46 years ) with chronic back pain referred to spine rehabilitation . Primary outcomes were back strength and progressive isoinertial lifting evaluation ( PILE ) at discharge . Secondary outcomes were Oswestry disability ( 0 - 100 ) and pain scores ( 0 - 10 ) . Exercises consisted of Cybex back extension , rotary torso , pull downs , and multi-hip ; lifting of crates from floor-to-waist ( lumbar ) and waist-to-shoulder ( cervical ) heights . The maximum levels of exercises were determined using a four repetition to maximum protocol , and the PILE . RESULTS At discharge , there was no significant difference in strength , disability or pain measures between subjects completing 1 versus 2 sets of resistance exercises . CONCLUSION These findings suggest that there were no added benefits for completing a second set of resistance exercises during therapy sessions for patients with CLBP UNLABELLED This r and omized , double-blind , placebo-controlled study assessed efficacy and safety of duloxetine in patients with chronic low back pain ( CLBP ) . Adults ( n = 401 ) with a nonneuropathic CLBP and average pain intensity of ≥ 4 on an 11-point numerical scale ( Brief Pain Inventory [ BPI ] ) were treated with either duloxetine 60 mg once daily or placebo for 12 weeks . The primary measure was BPI average pain . Secondary endpoints included Patient 's Global Impressions of Improvement ( PGI-I ) , Rol and Morris Disability Question naire ( RMDQ-24 ) , BPI-Severity ( BPI-S ) , BPI-Interference ( BPI-I ) , and response rates ( either ≥ 30 % or ≥ 50 % BPI average pain reduction at endpoint ) . Health outcomes included Short Form-36 , European Quality of Life-5 Dimensions , and the Work Productivity and Activity Impairment question naire . Safety and tolerability were assessed . Compared with placebo-treated patients , duloxetine-treated patients reported a significantly greater reduction in BPI average pain ( P ≤ .001 ) . Similarly , duloxetine-treated patients reported significantly greater improvements in PGI-I , BPI-S , BPI-I , 50 % response rates , and some health outcomes . The RMDQ and 30 % response rate showed numerical improvements with duloxetine treatment . Significantly more patients in the duloxetine group ( 15.2 % ) than patients in the placebo group ( 5.4 % ) discontinued because of adverse events ( P = .002 ) . Nausea and dry mouth were the most common treatment-emergent adverse events with rates significantly higher in duloxetine-treated patients . PERSPECTIVE This study provides clinical evidence of the efficacy and safety of duloxetine at a fixed dose of 60 mg once daily in the treatment of chronic low back pain ( CLBP ) . As of December 2009 , duloxetine has not received regulatory approval for the treatment of CLBP Study Design . Sixteen-week intervention for chronic patients with low back pain ( LBP ) with 9-month follow-up . Primary r and omization at 4 weeks into either supervised Swiss ball exercise or an exercise advice group . Objective . To evaluate changes in disability and pain in individuals with chronic LBP after combined treatment and exercise interventions , and to evaluate whether changes in self-report or physical measures would best explain improvements in disability Summary of Background Data . There is a need to underst and what the effectiveness of a clinical ly applicable treatment intervention is for an individual ’s perception of their back pain . There is insufficient evidence about the different combinations of manual treatment that commonly precede involvement in exercise programs . Methods . Sixty individuals with chronic nonspecific LBP ( at least 3-month duration ) were r and omly assigned ( after 4 weeks of manipulative or nonmanipulative treatment ) to either a supervised Swiss ball exercise group , or an advice group . The exercise intervention was for 12 weeks with a long-term follow-up of 9 months . Self-report measures and physical measures ( endurance times and myoelectric fatigue ) were collected throughout the study . Results . Self-rated disability improved more after the treatment period for individuals who received supervised exercise compared with advice alone . There was no difference found between individuals who received manipulative or nonmanipulative treatment . Multiple regression analysis found that self-report measures best explained improvements in disability throughout the study . Long-term findings showed no group differences . Conclusion . Supervised exercise is a more successful subsequent to manual treatment compared with exercise advice . The improvements associated with this type of program were primarily manifested in the psychologic self-report measures rather than physical measurements Introduction Patients ' initial beliefs about the success of a given pain treatment are shown to affect final treatment outcome . The Credibility/Expectancy Question naire ( CEQ ) has recently been developed as measure of treatment credibility and expectancy . Objective The objectives of this study were ( 1 ) to investigate the factor structure of the CEQ in a sample of chronic low back pain ( CLBP ) patients by means of a confirmatory factor analysis , ( 2 ) to examine the association between treatment credibility and expectancy and patient characteristics , and ( 3 ) to assess whether treatment expectancy and credibility are associated with the outcome of rehabilitation treatment . Methods CLBP patients ( n=167 ) were r and omized to either active physical therapy ( n=51 ) , cognitive-behavioral therapy ( n=57 ) , or a combination therapy ( n=59 ) , and completed the CEQ after a careful explanation of the treatment rationale . Results Confirmatory factor analysis supported the 2-factor structure ( credibility/expectancy ) of the CEQ . Lower credibility was associated with higher pain-related fear and lower internal control of pain , and lower expectancy with higher levels of pain-related fear and no radiating pain . Multiple linear regression analyses revealed that after controlling for age , sex , treatment center , pain-intensity at baseline , duration of disability , and irrespective of the treatment offered , expectancy was significantly associated with disability and satisfaction . Credibility was significantly associated with patient-specific symptoms and satisfaction . For global perceived effect , treatment expectancy was predictive in active physical therapy only , and treatment credibility was a significant predictor in combination therapy only . Discussion Although the associations found were low to modest , these results underscore the importance of expectancy and credibility for the outcome of different active interventions for CLBP and might contribute to the development of more effective treatments Objectives To evaluate the effects of early access ( EA ) to physical therapy treatment for patients with subacute low back pain compared to access with a 4-week waiting list . Design A prospect i ve , r and omized clinical trial . Setting Primary health care . Patients Sixty consecutive patients with subacute low back pain . Interventions Patients were r and omized either to EA within 2 days for physical examination and individualized physical therapy treatment ( n=32 ) or a control group with a 4-week waiting list ( n=28 ) . Outcome Measures Self-administrated question naires were used for assessment at inclusion , at discharge , and at 6 months . Primary outcome measure was pain intensity assessed by Borg category scale for ratings of perceived pain . Secondary outcomes included the Örebro musculoskeletal pain screening question naire , the Rol and and Morris disability question naire , sick-leave , visits to health care , and physical therapy . Results The results showed no significant differences in pain between the groups at discharge . At 6 months , the reduction of pain was significantly greater in the EA group compared to the control group ( P=0.025 ) . Changes in secondary outcome measures were not significantly different between groups . Conclusions This study indicated that EA to physical therapy result ed in greater improvement in perceived pain at 6 months compared to later access . In this study , EA to physical therapy could be introduced by reorganization without additional re sources BACKGROUND We aim ed to investigate whether the addition of non-steroidal anti-inflammatory drugs or spinal manipulative therapy , or both , would result in faster recovery for patients with acute low back pain receiving recommended first-line care . METHODS 240 patients with acute low back pain who had seen their general practitioner and had been given advice and paracetamol were r and omly allocated to one of four groups in our community-based study : diclofenac 50 mg twice daily and placebo manipulative therapy ( n=60 ) ; spinal manipulative therapy and placebo drug ( n=60 ) ; diclofenac 50 mg twice daily and spinal manipulative therapy ( n=60 ) ; or double placebo ( n=60 ) . The primary outcome was days to recovery from pain assessed by survival curves ( log-rank test ) in an intention-to-treat analysis . This trial was registered with the Australian Clinical Trials Registry , ACTRN012605000036617 . FINDINGS Neither diclofenac nor spinal manipulative therapy appreciably reduced the number of days until recovery compared with placebo drug or placebo manipulative therapy ( diclofenac hazard ratio 1.09 , 95 % CI 0.84 - 1.42 , p=0.516 ; spinal manipulative therapy hazard ratio 1.01 , 95 % CI 0.77 - 1.31 , p=0.955 ) . 237 patients ( 99 % ) either recovered or were censored 12 weeks after r and omisation . 22 patients had possible adverse reactions including gastrointestinal disturbances , dizziness , and heart palpitations . Half of these patients were in the active diclofenac group , the other half were taking placebo . One patient taking active diclofenac had a suspected hypersensitivity reaction and ceased treatment . INTERPRETATION Patients with acute low back pain receiving recommended first-line care do not recover more quickly with the addition of diclofenac or spinal manipulative therapy OBJECTIVES Both exercises and manipulation are recommended as basic therapy in back diseases , while a possible synergistic effect of these treatments have not been clarified . This study was conducted to test a possible further effect of manipulation as adjunct to extension exercises for unspecific LBP . METHODS 72 patients with chronic LBP ( mean 12 months ) were examined by a specialist in manual medicine , who detected localized binding between the lumbar segments . All patients were instructed in extension exercises , while r and omized to either pretreatment with specific manipulation or control . The patients were blinded to the manipulation , which was performed at the end of the manual examination , and repeated after two and four weeks . The manipulator only knew the group of the particular patient just before manipulation by the end of the examination . The primary end point was pain , measured by a visual analogue scale . RESULTS Pain in both back and leg decreased without differences between groups . Segmental binding of the low-back was associated with persisting clinical symptoms at four weeks . CONCLUSION No additional effect was demonstrated of manipulation , when extension exercises were used as basic therapy BACKGROUND Chronic low back pain is a common problem lacking highly effective treatment options . Small trials suggest that yoga may have benefits for this condition . This trial was design ed to determine whether yoga is more effective than conventional stretching exercises or a self-care book for primary care patients with chronic low back pain . METHODS A total of 228 adults with chronic low back pain were r and omized to 12 weekly classes of yoga ( 92 patients ) or conventional stretching exercises ( 91 patients ) or a self-care book ( 45 patients ) . Back-related functional status ( modified Rol and Disability Question naire , a 23-point scale ) and bothersomeness of pain ( an 11-point numerical scale ) at 12 weeks were the primary outcomes . Outcomes were assessed at baseline , 6 , 12 , and 26 weeks by interviewers unaware of treatment group . RESULTS After adjustment for baseline values , 12-week outcomes for the yoga group were superior to those for the self-care group ( mean difference for function , -2.5 [ 95 % CI , -3.7 to -1.3 ] ; P < .001 ; mean difference for symptoms , -1.1 [ 95 % CI , -1.7 to -0.4 ] ; P < .001 ) . At 26 weeks , function for the yoga group remained superior ( mean difference , -1.8 [ 95 % CI , -3.1 to -0.5 ] ; P < .001 ) . Yoga was not superior to conventional stretching exercises at any time point . CONCLUSION Yoga classes were more effective than a self-care book , but not more effective than stretching classes , in improving function and reducing symptoms due to chronic low back pain , with benefits lasting at least several months . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00447668 Study Design . Original study . Objective . Prospect i ve comparison of clinical outcomes after a st and ard posterior lumbar interbody fusion ( ST-PLIF ) and after a limited exposure PLIF incorporating total facetectomy ( LI-PLIF ) . Summary of Background Data . Most groups have reported significantly improved clinical outcomes after ST-PLIF . To our knowledge , however , a comparison of outcomes between ST-PLIF and the LI-PLIF that we herein describe has not been reported before . Methods . Patients were included who had suffered chronic low back pain for a minimum of 2 years that was unresponsive to conservative treatment . N = 114 consecutive patients underwent ST-PLIF , whereas n = 209 underwent LI-PLIF . All patients underwent pre- and postoperative evaluations for Oswestry Disability Index ( ODI ) , short-form 36 ( SF-36 ) , and visual analogue scores ( VAS ) . The minimum follow-up for either group was 2 years . Results . There was a significant improvement in the ODI ( 22.5 ± 1.0 , P < 0.001 ) , VAS for back pain ( 3.8 ± 0.1 , P = 0.003 ) , VAS for leg pain ( 4.0 ± 0.2 , P = 0.002 ) , and SF-36 for bodily pain ( 14.7 ± 0.9 , P = 0.012 ) after ST-PLIF . However , there was a significantly greater improvement in all scores after LI-PLIF : ODI ( 28.8 ± 1.4 vs. 22.5 ± 1.0 , P < 0.001 ) , VAS for back pain ( 5.4 ± 0.2 vs. 3.8 ± 0.1 , P = 0.001 ) , VAS for leg pain ( 5.1 ± 0.2 vs. 4.0 ± 0.2 , P < 0.001 ) , and SF-36 for bodily pain ( 18.5 ± 0.8 vs. 14.7 ± 0.9 , P = 0.003 ) . There was a significantly shorter duration of hospital stay after LI-PLIF ( 2.24 ± 0.057 days ) than after ST-PLIF ( 4.04 ± 0.13 days ) ( P = 0.005 ) . Operative complications occurred in 19.3 % of ST-PLIF and in 6.7 % of LI-PLIF . Conclusion . Clinical outcomes were significantly improved after both ST-PLIF and LI-PLIF . However , outcomes were significantly better after LI-PLIF than after ST-PLIF . Significantly shortened hospital stay with LI-PLIF probably reflected the “ less invasive ” technique per se . Significantly better clinical outcomes with fewer complications after LI-PLIF , however , potentially reflected maneuvers singular to LI-PLIF : ( 1 ) preservation of posterior elements , ( 2 ) avoidance of far lateral dissection over the transverse processes , ( 3 ) bilateral total facetectomy , ( 4 ) fewer neurologic complications , and ( 5 ) avoidance of iliac crest autograft . LI-PLIF is therefore recommended over ST-PLIF BACKGROUND AND PURPOSE Improving functional performance in patients with chronic low back pain is of primary importance . The purpose of this study was to examine the effects of 2 proprioceptive neuromuscular facilitation ( PNF ) programs on trunk muscle endurance , flexibility , and functional performance in subjects with chronic low back pain ( CLBP ) . SUBJECTS Eighty-six women ( 40.2+/-11.9 [ mean+/-SD ] years of age ) who had complaints of CLBP were r and omly assigned to 3 groups : rhythmic stabilization training , combination of isotonic exercises , and control . METHODS Subjects trained with each program for 4 weeks with the aim of improving trunk stability and strength . Static and dynamic trunk muscle endurance and lumbar mobility were measured before , at the end of , and 4 and 8 weeks after training . Disability and back pain intensity also were measured with the Oswestry Index . RESULTS Multivariate analysis of variance indicated that both training groups demonstrated significant improvements in lumbar mobility ( 8.6%-24.1 % ) , static and dynamic muscle endurance ( 23.6%-81 % ) , and Oswestry Index ( 29.3%-31.8 % ) measurements . DISCUSSION AND CONCLUSION Static and dynamic PNF programs may be appropriate for improving short-term trunk muscle endurance and trunk mobility in people with CLBP Low back pain ( LBP ) poses a significant problem to society . Although initial conservative therapy may be beneficial , persisting chronic LBP still frequently leads to expensive invasive intervention . A novel non-invasive therapy that focuses on discogenic LBP is Intervertebral Differential Dynamics Therapy ® ( IDD Therapy , North American Medical Corp. Reg U.S. ) . IDD Therapy consists of intermittent traction sessions in the Accu-SPINA device ( Steadfast Corporation Ltd , Essex , UK ) , an FDA approved , class II medical device . The intervertebral disc and facet joints are unloaded through axial distraction , positioning and relaxation cycles . The purpose of this study is to investigate the effect of IDD Therapy when added to a st and ard grade d activity program for chronic LBP patients . In a single blind , single centre , r and omized controlled trial ; 60 consecutive patients were assigned to either the SHAM or the IDD Therapy . All subjects received the st and ard conservative therapeutic care ( grade d activity ) and 20 sessions in the Accu-SPINA device . The traction weight in the IDD Therapy was systematic ally increased until 50 % of a person ’s body weight plus 4.45 kg ( 10 lb ) was reached . The SHAM group received a non-therapeutic traction weight of 4.45 kg in all sessions . The main outcome was assessed using a 100-mm visual analogue scale ( VAS ) for LBP . Secondary outcomes were VAS scores for leg pain , Oswestry Disability Index ( ODI ) , Short-Form 36 ( SF-36 ) . All parameters were measured before and 2 , 6 and 14 weeks after start of the treatment . Fear of (re)injury due to movement or activities ( Tampa Scale for Kinesiophobia ) , coping strategies ( Utrecht Coping List ) and use of pain medication were recorded before and at 14 weeks . A repeated measures analysis was performed . The two groups were comparable at baseline in terms of demographic , clinical and psychological characteristics , indicating that the r and om allocation had succeeded . VAS low back pain improved significantly from 61 ( ±25 ) to 32 ( ±27 ) with the IDD protocol and 53 ( ±26 ) to 36 ( ±27 ) in the SHAM protocol . Moreover , leg pain , ODI and SF-36 scores improved significantly but in both groups . The use of pain medication decreased significantly , whereas scores for kinesiophobia and coping remained at the same non-pathological level . None of the parameters showed a difference between both protocol s. Both treatment regimes had a significant beneficial effect on LBP , leg pain , functional status and quality of life after 14 weeks . The added axial , intermittent , mechanical traction of IDD Therapy to a st and ard grade d activity program has been shown not to be effective UNLABELLED In this enriched design study , 1,160 opioid-experienced patients with chronic , moderate to severe low back pain entered an open-label run-in period ; 660 demonstrated analgesic benefit from and tolerability to buprenorphine transdermal system 20 mcg/hour ( BTDS 20 ) treatment and were r and omized to receive either BTDS 20 , BTDS 5 mcg/hour ( BTDS 5 ) , or the active control ( immediate release oxycodone 40-mg/day ) during an 84-day double-blind phase . The primary endpoint , " average pain in the last 24 hours " during double-blind weeks 4 , 8 , and 12 , was significantly lower for patients receiving BTDS 20 compared with patients receiving BTDS 5 ( P < .001 , treatment difference of -.67 ) . A treatment difference of -.75 in favor of oxycodone 40 mg/day versus BTDS 5 ( P < .001 ) indicated the assay sensitivity of the study . Four sensitivity analyses , secondary , and exploratory analyses supported the results of the primary analysis . Incidences of treatment-emergent adverse events were 56 % during the open-label period , and 59 , 77 , and 73 % for the BTDS 5 , BTDS 20 , and oxycodone 40 mg/day treatment groups , respectively , during the double-blind phase . One death considered unrelated to study treatment occurred in a patient receiving BTDS 10 during the run-in period . BTDS 20 treatment was demonstrated to be efficacious and generally well tolerated . PERSPECTIVE This article presents results of a pivotal Phase 3 study that assesses a new treatment for the management of chronic low back pain : a transdermal patch containing the opioid buprenorphine ( BTDS ) . In this active controlled , superiority study with an enriched design , BTDS 20 was found to be efficacious and generally well tolerated STUDY DESIGN AND OBJECTIVE The ACTION trial , an open-label , r and omized , multicenter , two-part study , compared the efficacy and safety of two sustained-release opioids ( SROs ) , A VINZA ( A-MQD ) , morphine sulfate extended-release capsules given once a day , and OxyContin ( O-ER ) , oxycodone modified-release tablets given twice a day , in subjects with chronic , moderate to severe low back pain . The first part of the study , the evaluation phase , was followed by an optional four-month extension phase aim ed at evaluating the long-term stability of pain control , SRO dose , and quality of sleep . RESULTS Three hundred and ninety-two subjects were enrolled in the study ; 220 completed the evaluation phase , and 174 entered the extensionphase . During the latterphase , subjects in the A-MQD group ( n=79 ) continued to report lower pain scores , better quality of sleep , lower daily morphine-equivalent doses ( means of 86 mg versus 119 mg ) , and a comparable usage of ibuprofen compared to subjects in the O-ER group ( n=95 ) . The incidence and severity of elicited opioid side effects were similar between the two groups . CONCLUSIONS Both study drugs result ed in significant pain relief and improved sleep in SRO-naive patients with chronic low back pain , and this outcome was attained with a stable daily SRO dose . In patients who completed opioid dose titration , A VINZA performed significantly better than OxyContin in reducing pain scores and improving sleep-with a lower morphine-equivalent daily dose-during both the evaluation and extension phases CONTEXT This article presents the results of a pivotal Phase 3 study that assesses a new treatment for the management of chronic low back pain : a transdermal patch containing the opioid buprenorphine . In this r and omized , placebo-controlled study with an enriched enrollment design , the buprenorphine transdermal system ( BTDS ) was found to be efficacious and generally well tolerated . OBJECTIVES This enriched , multicenter , r and omized , double-blind study evaluated the efficacy , tolerability , and safety of BTDS in opioid-naïve patients who had moderate to severe chronic low back pain . METHODS Patients who tolerated and responded to BTDS ( 10 or 20 mcg/hour ) during an open-label run-in period were r and omized to continue BTDS 10 or 20 mcg/hour or receive matching placebo . The primary outcome was " average pain over the last 24 hours " at the end of the 12-week double-blind phase , collected on an 11-point scale ( 0=no pain , 10=pain as bad as you can imagine ) . Sleep disturbance ( Medical Outcomes Study subscale ) and total number of supplemental analgesic tablets used were secondary efficacy variables . RESULTS Fifty-three percent of patients receiving open-label BTDS ( 541 of 1024 ) were r and omized to receive BTDS ( n=257 ) or placebo ( n=284 ) . Patients receiving BTDS reported statistically significantly lower pain scores at Week 12 compared with placebo ( least square mean treatment difference : -0.58 , P=0.010 ) . Sensitivity analyses of the primary efficacy variable and results of the analysis of secondary efficacy variables supported the efficacy of BTDS relative to placebo . During the double-blind phase , the incidence of treatment-emergent adverse events was 55 % for the BTDS treatment group and 52 % for the placebo treatment group . Laboratory , vital sign , and electrocardiogram evaluations did not reveal unanticipated safety findings . CONCLUSION BTDS was efficacious in the treatment of opioid-naïve patients with moderate to severe chronic low back pain . Most treatment-emergent adverse events observed were consistent with those associated with the use of opioid agonists and transdermal patches BACKGROUND Low-back pain is a common and costly problem . We estimated the effectiveness of a group cognitive behavioural intervention in addition to best practice advice in people with low-back pain in primary care . METHODS In this pragmatic , multicentre , r and omised controlled trial with parallel cost-effectiveness analysis undertaken in Engl and , 701 adults with troublesome subacute or chronic low-back pain were recruited from 56 general practice s and received an active management advisory consultation . Participants were r and omly assigned by computer-generated block r and omisation to receive an additional assessment and up to six sessions of a group cognitive behavioural intervention ( n=468 ) or no further intervention ( control ; n=233 ) . Primary outcomes were the change from baseline in Rol and Morris disability question naire and modified Von Korff scores at 12 months . Assessment of outcomes was blinded and followed the intention-to-treat principle , including all r and omised participants who provided follow-up data . This study is registered , number IS RCT N54717854 . FINDINGS 399 ( 85 % ) participants in the cognitive behavioural intervention group and 199 ( 85 % ) participants in the control group were included in the primary analysis at 12 months . The most frequent reason for participant withdrawal was unwillingness to complete question naires . At 12 months , mean change from baseline in the Rol and Morris question naire score was 1.1 points ( 95 % CI 0.39 - 1.72 ) in the control group and 2.4 points ( 1.89 - 2.84 ) in the cognitive behavioural intervention group ( difference between groups 1.3 points , 0.56 - 2.06 ; p=0.0008 ) . The modified Von Korff disability score changed by 5.4 % ( 1.99 - 8.90 ) and 13.8 % ( 11.39 - 16.28 ) , respectively ( difference between groups 8.4 % , 4.47 - 12.32 ; p<0.0001 ) . The modified Von Korff pain score changed by 6.4 % ( 3.14 - 9.66 ) and 13.4 % ( 10.77 - 15.96 ) , respectively ( difference between groups 7.0 % , 3.12 - 10.81 ; p<0.0001 ) . The additional quality -adjusted life-year ( QALY ) gained from cognitive behavioural intervention was 0.099 ; the incremental cost per QALY was 1786 pound sterling , and the probability of cost-effectiveness was greater than 90 % at a threshold of 3000 pound sterling per QALY . There were no serious adverse events attributable to either treatment . INTERPRETATION Over 1 year , the cognitive behavioural intervention had a sustained effect on troublesome subacute and chronic low-back pain at a low cost to the health-care provider . FUNDING National Institute for Health Research Health Technology Assessment Programme Study Design . R and omized controlled trial with 1-year follow-up . Objective . To analyze the effects of an exercise program or routine follow-up on patients with chronic low back pain who have completed functional multidisciplinary rehabilitation . The short- and long-term outcome in terms of symptoms and physical and social functioning was compared . Summary of Background Data . Systematic review s have shown that functional multidisciplinary rehabilitation improves physical function and reduces pain in patients with chronic low back pain . However , long-term maintenance of these improvements is inconsistent and the role of exercise in achieving this goal is unclear . Methods . One hundred five chronic patients with low back pain who had completed a 3-week functional multidisciplinary rehabilitation program were r and omized to either a 3-month exercise program ( n = 56 ) or routine follow-up ( n = 49 ) . The exercise program consisted of 24 training sessions during 12 weeks . Patients underwent evaluations of trunk muscle endurance , cardiovascular endurance , lumbar spine mobility ( flexion and extension range-of-motion , fingertip-to-floor distance ) , pain and perceived functional ability at the beginning and the end of functional multidisciplinary rehabilitation , at the end of the exercise program ( 3 months ) and at 1-year follow-up . Disability was also assessed at the same time points except at the beginning of functional multidisciplinary rehabilitation . Results . At the end of the functional multidisciplinary rehabilitation , both groups improved significantly in all physical parameters except flexion and extension range-of-motion . At the 3 month and 1 year follow-up , both groups maintained improvements in all parameters except for cardiovascular endurance . Only the exercise program group improved in disability score and trunk muscle endurance . No differences between groups were found . Conclusion . A favorable long-term outcome was observed after functional multidisciplinary rehabilitation in both patient groups . Patients who participated in an exercise program obtained some additional benefits . The relevance of these benefits to overall health status need to be further investigated OBJECTIVE This study determines the efficacy of two such multimodal treatments in the management of lumbar pain syndrome in males and females . METHOD Total subjects of 141 male or female were r and omized to treat either with conventional treatment or by DMST ( dynamic muscular stabilization techniques ) . After stratification on the basis of gender ( 51 male and 21 female ) were found in DMST group whereas ( 40 male and 29 female ) were found in conventional group . The primary outcome measures were pain severity , physical strength ( BPC and APC ) , functional ability ( Walking , Stairs climbing and St and -ups ) and QOL . All patients were assessed at baseline ( day 0 ) , 10 days , 20 days , 90 days and at the end treatment or follow up ( day 180 ) . RESULT In this study the improvement of pain , BPC , APC , Walking , Stair climbing and st and -ups in females and males were 22.5 % and 29.0 % , 60.9 % and 53.7 % , 42.0 % and 51.9 % , 49.8 % and 49.3 % , 54.2 % and 48.7 % , 52.3 % and 39.7 % , higher respectively in DMST as compared to CONV whereas QOL in females of DMST improved by 53.6 % more than the females of CONV while males of DMST improved by 57.9 % more than the males of CONV . CONCLUSION DMST as well as CONV treatments are more effective in males than the females . Study also concluded that subgroup " female " may need more clinical attention during the management of LBP The aim of this study was to assess changes in deep abdominal muscle function after 8 weeks of exercise in chronic low back pain patients . Patients ( n = 109 ) were r and omized to specific ultrasound guided , sling or general exercises . Contraction thickness ratio in transversus abdominis ( TrA ) , obliquus internus ( OI ) and externus ( OE ) , and TrA lateral slide were assessed during the abdominal drawing-in maneuver by b-mode ultrasound . Changes in abdominal muscle function were also regressed on changes in pain . Only modest effects in deep abdominal muscle function were observed , mainly due to reduced activation of OI ( contraction thickness ratio : 1.42 - 1.22 , p = 0.01 ) and reduced TrA lateral slide ( 1.26 - 1.01 cm , p = 0.02 ) in the ultrasound group on the left side . Reduced pain was associated with increased TrA and reduced OI contraction ratio ( R(2 ) = 0.18 ) . It is concluded that 6 - 8 treatments with specific or general exercises for chronic low back patients attained only marginal changes in contraction thickness and slide in deep abdominal muscles , and could only to a limited extent account for reductions in pain Objectives : The aim of this study on persons with nonspecific chronic low back pain was to evaluate the effect of a multimodal physical therapy program with or without the addition of deep-water running on pain , physical disability , and general health . Design : A r and omized controlled trial involving 46 subjects with nonspecific chronic low back pain were treated three times a week for 15 wks . Each group received 60 mins of multimodal physical therapy program ( an individualized exercise program ; manual therapy ; and back care , pain education , and information on an active lifestyle ) , whereas one group performed additional 20-min sessions of deep-water running at an individual workload of the aerobic threshold . Results : Both interventions result ed in significant improvements in pain , disability , and physical health . The mean change in pain , disability , and physical health state were −36.1 ± 25.1 mm on the visual analog scale , −3.0 ± 4.8 points for the Rol and Morris Question naire , and 10.6 ± 12.9 points for the Short Form-12 for the physical therapy plus deep-water running group and −34.1 ± 26.0 mm on the visual analog scale , −1.6 ± 1.5 points for the Rol and Morris Question naire , and 8.9 ± 13.0 points for the Short Form-12 for the physical therapy alone group . Conclusions : Pain , disability , health status , muscle strength and endurance , and lumbar range of motion significantly improved in both groups . The addition of a deep-water running program at an individual workload of the aerobic threshold to the multimodal physical therapy program produced a significant improvement in pain in patients with nonspecific chronic low back pain , but this was not significantly different when compared with multimodal physical therapy program alone . Disability , health status , muscle strength and endurance , and lumbar range of motion significantly improved to a similar level in both intervention groups OBJECTIVES To estimate the clinical effectiveness of active management ( AM ) in general practice versus AM plus a group-based , professionally led cognitive behavioural approach ( CBA ) for subacute and chronic low back pain ( LBP ) and to measure the cost of each strategy over a period of 12 months and estimate cost-effectiveness . DESIGN Pragmatic multicentred r and omised controlled trial with investigator-blinded assessment of outcomes . SETTING Fifty-six general practice s from seven English regions . PARTICIPANTS People with subacute and chronic LBP who were experiencing symptoms that were at least moderately troublesome . INTERVENTIONS Participants were r and omised ( in a ratio of 2:1 ) to receive either AM+CBA or AM alone . MAIN OUTCOME MEASURES Primary outcomes were the Rol and Morris Disability Question naire ( RMQ ) and the Modified Von Korff Scale ( MVK ) , which measure LBP and disability . Secondary outcomes included mental and physical health-related quality of life ( Short Form 12-item health survey ) , health status , fear avoidance beliefs and pain self-efficacy . Cost-utility of CBA was considered from both the UK NHS perspective and a broader health-care perspective , including both NHS costs and costs of privately purchased goods and services related to LBP . Quality -adjusted life-years ( QALYs ) were calculated from the five-item EuroQoL. RESULTS Between April 2005 and April 2007 , 701 participants were r and omised : 233 to AM and 468 to AM+CBA . Of these , 420 were female . The mean age of participants was 54 years and mean baseline RMQ was 8.7 . Outcome data were obtained for 85 % of participants at 12 months . Benefits were seen across a range of outcome measures in favour of CBA with no evidence of group or therapist effects . CBA result ed in at least twice as much improvement as AM . Mean additional improvement in the CBA arm was 1.1 [ 95 % confidence interval ( CI ) 0.4 to 1.7 ] , 1.4 ( 95 % CI 0.7 to 2.1 ) and 1.3 ( 95 % CI 0.6 to 2.1 ) change points in the RMQ at 3 , 6 and 12 months respectively . Additional improvement in MVK pain was 6.8 ( 95 % CI 3.5 to 10.2 ) , 8.0 ( 95 % CI 4.3 to 11.7 ) and 7.0 ( 95 % CI 3.2 to 10.7 ) points , and in MVK disability was 4.3 ( 95 % CI 0.4 to 8.2 ) , 8.1 ( 95 % CI 4.1 to 12.0 ) and 8.4 ( 95 % CI 4.4 to 12.4 ) points at 3 , 6 and 12 months respectively . At 12 months , 60 % of the AM+CBA arm and 31 % of the AM arm reported some or complete recovery . Mean cost of attending a CBA course was 187 pounds per participant with an additional benefit in QALYs of 0.099 and an additional cost of 178.06 pounds . Incremental cost-effectiveness ratio was 1786.00 pounds . Probability of CBA being cost-effective reached 90 % at about 3000 pounds and remained at that level or above ; at a cost-effectiveness threshold of 20,000 pounds the CBA group had an almost 100 % probability of being considered cost-effective . User perspectives on the acceptability of group treatments were sought through semi-structured interviews . Most were familiar with key messages of AM ; most who had attended any group sessions had retained key messages from the sessions and two-thirds talked about a reduction in fear avoidance and changes in their behaviour . Group sessions appeared to provide reassurance , lessen isolation and enable participants to learn strategies from each other . CONCLUSIONS Long-term effectiveness and cost-effectiveness of CBA in treating subacute and chronic LBP was shown , making this intervention attractive to patients , clinicians and purchasers . Short-term ( 3-month ) clinical effects were similar to those found in high- quality studies of other therapies and benefits were maintained and increased over the long term ( 12 months ) . Cost per QALY was about half that of competing interventions for LBP and because the intervention can be delivered by existing NHS staff following brief training , the back skills training programme could be implemented within the NHS with relative ease . TRIAL REGISTRATION Current Controlled Trials IS RCT N37807450 . FUNDING The National Institute for Health Research Health Technology Assessment programme AIMS The present study examines the outcome of counselling in physiotherapy based on the Transtheoretical Model ( TTM ) in a sample of elderly individuals with chronic low back pain . METHODS In a prospect i ve r and omised trial with concealed assignment , elderly individuals with chronic low back pain were allocated to two treatment conditions . Both contained 10 sessions of physiotherapy , each of 20min duration . In addition , the experimental group ( EG ) received 10min counselling prior to every session based on the TTM , also provided by the physiotherapist , and the control group ( CG ) underwent a placebo ultrasound treatment with an inactivated device to control for the additional attention given to the EG . Assessment s took place prior to the treatment ( t1 ) , immediately after termination of the treatment ( t2 ) , and at a 6-months follow-up . Outcome measures were physical activity calculated from one-week activity diaries , self-reported functional capacity , and range of motion measured by ultrasound topometry . RESULTS A total of 170 individuals ( 64 % female ) with a mean age of 70.3 years ( SD=4.4 , range 65 - 84 ) participated in the study . The retention rate was 90 % . At t3 , both EG and CG showed increased physical activity and functional capacity , but no change in range of motion . Effect sizes were large . Contrary to our hypothesis , however , motivational training did not result in a better outcome compared with placebo treatment . CONCLUSION The study does not provide evidence that a short TTM-based motivation programme is superior to placebo treatment regarding adherence to activity recommendations BACKGROUND Tapentadol , a novel , central ly acting analgesic with 2 mechanisms of action ( mu-opioid receptor agonism and norepinephrine reuptake inhibition ) , has been developed in an immediate-release ( IR ) and an extended-release ( ER ) formulation . Determination of the safety and equianalgesic ratios for conversion between formulations is important for physicians with patients taking tapentadol IR who may want to switch to tapentadol ER , or vice versa , for any reason . OBJECTIVES To test whether the total daily dose ( TDD ) of tapentadol IR may be directly converted into a comparable TDD of tapentadol ER , and vice versa , with equivalent efficacy and comparable safety . STUDY DESIGN R and omized , double-blind , 2-period ( 2 weeks each ) crossover study . SETTING Study centers ( N = 13 ) in the United States . METHODS Patients with moderate to severe chronic low back pain received tapentadol IR 50 , 75 , or 100 mg every 4 or 6 hours ( maximum TDD , 500 mg ) during the 3-week open-label period to identify an optimal , stable dose of tapentadol IR for each patient . Patients were then r and omized in a 1:1 ratio to receive , during the first 2-week double-blind period , either the optimal dose of tapentadol IR identified during the open-label period or a TDD of tapentadol ER ( 100 , 150 , 200 , or 250 mg bid ) that was as close as possible to the TDD of tapentadol IR from the open-label period . During a subsequent , 2-week double-blind period , patients received whichever formulation was not received during the first double-blind period . The primary endpoint was the mean average daily pain intensity ( on an 11-point numerical rating scale ) during the last 3 days of each double-blind treatment period . If the 95 % confidence intervals ( CIs ) of the least squares mean difference between formulations were within the range of -2 to 2 , the formulations were considered equivalent . RESULTS Of the 88 patients who were r and omized , 72 completed both double-blind treatments , and 60 were included in the per- protocol analysis . The mean ( st and ard deviation [ SD ] ) pain intensity score decreased from 7.3 ( 1.19 ) pre-treatment to 4.2 ( 2.13 ) after 3 weeks of open-label treatment with tapentadol IR and remained constant throughout double-blind treatment ( 3.9 or 4.0 each week ) for both formulations . The mean ( SD ) of the average pain intensity scores over the last 3 days of double-blind treatment was 3.9 ( 2.17 ) with tapentadol IR and 4.0 ( 2.29 ) with tapentadol ER , for an estimated difference of 0.1 ( 95 % CI , -0.09 to 0.28 ) . For both tapentadol IR and tapentadol ER , the median TDD administered was 300.0 mg , and acetaminophen was used by 39.5 % and 45.2 % of patients , respectively . The incidence of treatment-emergent adverse events during double-blind treatment was similar between the tapentadol IR and tapentadol ER groups . LIMITATIONS Use of rescue medication theoretically could have influenced pain measurements , but in practice , pain measurements did not differ between treatments . CONCLUSIONS Approximately equivalent TDDs of tapentadol IR and tapentadol ER provided equivalent analgesic efficacy for the relief of moderate to severe chronic low back pain and were similarly well tolerated , allowing for direct conversion between the 2 formulations . CLINICAL TRIAL REGISTRATION NCT00594516 & NA ; Although chronic back pain is one of the most frequent reasons for permanent impairment in people under 65 , the neurobiological mechanisms of chronification remain vague . Evidence suggests that cortical reorganisation , so‐called functional plasticity , may play a role in chronic back pain patients . In the search for the structural counterpart of such functional changes in the CNS , we examined 18 patients suffering from chronic back pain with voxel‐based morphometry and compared them to 18 sex and age matched healthy controls . We found a significant decrease of gray matter in the brainstem and the somatosensory cortex . Correlation analysis of pain unpleasantness and the intensity of pain on the day of scanning revealed a strong negative correlation ( i.e. a decrease in gray matter with increasing unpleasantness/increasing intensity of pain ) in these areas . Additionally , we found a significant increase in gray matter bilaterally in the basal ganglia and the left thalamus . These data support the hypothesis that ongoing nociception is associated with cortical and subcortical reorganisation on a structural level , which may play an important role in the process of the chronification of pain Study Design . Pragmatic , multicentered r and omized controlled trial , with 12-month follow-up . Objective . To evaluate the effect of adding specific spinal stabilization exercises to conventional physiotherapy for patients with recurrent low back pain ( LBP ) in the United Kingdom . Summary of Background Data . Spinal stabilization exercises are a popular form of physiotherapy management for LBP , and previous small-scale studies on specific LBP subgroups have identified improvement in outcomes as a result . Methods . A total of 97 patients ( 18–60 years old ) with recurrent LBP were recruited . Stratified r and omization was undertaken into 2 groups : “ conventional , ” physiotherapy consisting of general active exercise and manual therapy ; and conventional physiotherapy plus specific spinal stabilization exercises . Stratifying variables used were laterality of symptoms , duration of symptoms , and Rol and Morris Disability Question naire score at baseline . Both groups received The Back Book , by Rol and et al. Back-specific functional disability ( Rol and Morris Disability Question naire ) at 12 months was the primary outcome . Pain , quality of life , and psychologic measures were also collected at 6 and 12 months . Analysis was by intention to treat . Results . A total of 68 patients ( 70 % ) provided 12-month follow-up data . Both groups showed improved physical functioning , reduced pain intensity , and an improvement in the physical component of quality of life . Mean change in physical functioning , measured by the Rol and Morris Disability Question naire , was −5.1 ( 95 % confidence interval −6.3 to −3.9 ) for the specific spinal stabilization exercises group and −5.4 ( 95 % confidence interval −6.5 to −4.2 ) for the conventional physiotherapy group . No statistically significant differences between the 2 groups were shown for any of the outcomes measured , at any time . Conclusions . Patients with LBP had improvement with both treatment packages to a similar degree . There was no additional benefit of adding specific spinal stabilization exercises to a conventional physiotherapy package for patients with recurrent LBP Study design . Population -based r and omized controlled trial . Objective . To assess the effectiveness of workplace intervention and grade d activity , separately and combined , for multidisciplinary rehabilitation of low back pain ( LBP ) . Summary of Background Data . Effective components for multidisciplinary rehabilitation of LBP are not yet established . Methods . Participants sick-listed 2 to 6 weeks due to nonspecific LBP were r and omized to workplace intervention ( n = 96 ) or usual care ( n = 100 ) . Workplace intervention consisted of workplace assessment , work modifications , and case management involving all stakeholders . Participants still sick-listed at 8 weeks were r and omized for grade d activity ( n = 55 ) or usual care ( n = 57 ) . Grade d activity comprised biweekly 1-hour exercise sessions based on operant-conditioning principles . Outcomes were lasting return to work , pain intensity and functional status , assessed at baseline , and at 12 , 26 , and 52 weeks after the start of sick leave . Results . Time until return to work for workers with workplace intervention was 77 versus 104 days ( median ) for workers without this intervention ( P = 0.02 ) . Workplace intervention was effective on return to work ( hazard ratio = 1.7 ; 95 % CI , 1.2–2.3 ; P = 0.002 ) . Grade d activity had a negative effect on return to work ( hazard ratio = 0.4 ; 95 % CI , 0.3–0.6 ; P < 0.001 ) and functional status . Combined intervention had no effect . Conclusion . Workplace intervention is advised for multidisciplinary rehabilitation of subacute LBP . Grade d activity or combined intervention is not advised Study Design . R and omized clinical trial . Objectives . To evaluate the effectiveness of a back support plus education versus education alone in promoting recovery from a work-related low back disorder ( WR-LBD ) while simultaneously considering personal , health , and occupational factors and the impact of occupational factors on recovery . Summary of Background Data . No r and omized studies of active industrial workers with low back disorders exist regarding the effectiveness of back supports plus education . Methods . A total of 433 actively employed hourly union workers who had a recent diagnosis of a WR-LBD : 1 ) those who wore a specially design ed back support plus received education on back health ; and 2 ) those who received education on back health only . Demographic , health , medical , and occupational factors were obtained through interview or abstract ion of computer files ; individual ergonomic exposures were measured with a lumbar motion monitor . Outcomes evaluated over a 12-month period included : self-reported measures of back pain , back pain disability level , physical health , mental health , and administrative measures of recurrence , lost work time , and medical care utilization . Results . There was no difference between the study groups with respect to mental or physical health , low back pain , back pain disability , neurogenic symptoms , lost work time , likelihood of recurrence of an episode of a back disorder , or other administrative measures of healthcare utilization or lost work time . However , significant decreases in low back pain , low back pain disability , neurogenic symptoms , and an increase in physical health were observed over the 12 months of observation in both study groups . The only occupational variable found to influence was plant group whereby service parts operations workers in the back support plus education group experienced a lower likelihood of WR-LBD recurrence . Conclusion . Although there was no overall effect on self-reported recovery or administrative measures or lost work time between the study groups , a back support plus health education may have some value in preventing recurrent WR-LBD in industrial workers who work in psychosocial environments and perform manual material h and ling tasks similar to those found in parts distribution centers OBJECTIVE Guidelines for the management of acute low back pain in primary care recommend early intervention to address psychosocial risk factors associated with long-term disability . We assessed the cost utility and cost effectiveness of a brief pain management program ( BPM ) targeting psychosocial factors compared with physical therapy ( PT ) for primary care patients with low back pain of < 12 weeks ' duration . METHODS A total of 402 patients were r and omly assigned to BPM or PT . We adopted a health care perspective , examining the direct health care costs of low back pain . Outcome measures were quality -adjusted life years ( QALYs ) and 12-month change scores on the Rol and and Morris disability question naire . Re source use data related to back pain were collected at 12-month followup . Cost effectiveness was expressed as incremental ratios , with uncertainty assessed using cost-effectiveness planes and acceptability curves . RESULTS There were no statistically significant differences in mean health care costs or outcomes between treatments . PT had marginally greater effectiveness at 12 months , albeit with greater health care costs ( BPM 142 pounds , PT 195 pounds ) . The incremental cost-per-QALY ratio was 2,362 pounds . If the UK National Health Service were willing to pay 10,000 pound per additional QALY , there is only a 17 % chance that BPM provides the best value for money . CONCLUSION PT is a cost-effective primary care management strategy for low back pain . However , the absence of a clinical ly superior treatment program raises the possibility that BPM could provide an additional primary care approach , administered in fewer sessions , allowing patient and doctor preferences to be considered OBJECTIVE To assess the efficacy and tolerability of flupirtine in comparison with tramadol for the treatment of moderate to severe subacute low back pain ( LBP ) . DESIGN AND METHODS In this r and omised , double-blind , parallel-group trial , 209 LBP patients , aged 18 - 65 years , were orally treated with flupirtine 100 mg ( n = 105 ) vs. tramadol 50 mg ( n = 104 ) , both three times daily for 5 - 7 days . MAIN OUTCOME MEASURES Patient assessment of pain intensity after 5 - 7 days ( primary ) ; physicians ' global assessment of improvement in pain and functional capacity ; adverse events . RESULTS Flupirtine showed an overall pain-relieving efficacy comparable to tramadol . Mean LBP intensity after end of treatment dropped from 6.8 ( 95 % CI : 6.5 - 7.0 ) to 2.8 ( 95 % CI : 2.3 - 3.1 ) for flupirtine and from 6.9 ( 95 % CI : 6.6 - 7.1 ) to 3.0 ( 95 % CI : 2.6 - 3.4 ) for tramadol , corresponding to pain relief rates of 57 % ( 95 % CI : 51 - 63 % ) and 56 % ( 95 % CI : 50 - 62 % ) respectively ( p = 0.796 ) , indicating non-inferiority of flupirtine . All other efficacy endpoints supported equivalent efficacy . Adverse events ( AEs ) occurred significantly less in patients after flupirtine ( 33 % ) vs. tramadol ( 49 % ) ( p = 0.02 ) and both the respective severity grading and the AE-related dropout rates were significantly lower after flupirtine than after tramadol ( 1 % vs. 15 % , p < 0.001 ) . CONCLUSION Flupirtine 100 mg three times daily was associated with a reduction in pain and improvements in functional capacity equivalent to that observed with tramadol 50 mg three times daily , and was better tolerated , when administered to patients with subacute back pain for one week . The limitations of this study were the lack of a placebo control and the short ( 7-day ) duration of the study Abstract Background : Carisoprodol , a central ly active skeletal muscle relaxant , is widely used for the treatment of acute , painful musculoskeletal disorders . When administered at a dose of 350 mg four times daily , carisoprodol demonstrated significant clinical benefit in its early clinical development trials ; however , some unfavorable side effects , such as drowsiness and dizziness , were reported . Recently , research was conducted to determine if a lower dose of carisoprodol would retain efficacy but improve tolerability compared to the higher 350-mg dose . Objective : The purpose of this multicenter study was to compare the efficacy and safety of carisoprodol 250-mg tablets four times daily to 350-mg tablets four times daily and to placebo in patients with acute , painful musculoskeletal spasm of the lower back . Research design and methods : In this 1-week double-blind , placebo-controlled , parallel-group multicenter trial , patients 18 to 65 years of age with moderate to severe back spasm were r and omly assigned to treatment with carisoprodol 250-mg tablets ( n = 264 ) , 350-mg tablets ( n = 273 ) , or matching placebo tablets ( n = 269 ) three times daily and at bedtime . Main outcome measures : The co primary efficacy variables were patient-rated relief from starting backache and patient-rated global impression of change assessed on treatment day 3 . Results : The carisoprodol 250-mg regimen was significantly more effective than placebo as assessed by both patient-rated relief from starting backache ( p = 0.0001 ) and patient-rated global impression of change ( p = 0.0046 ) . There were no significant differences between the 250-mg and 350-mg dosages for the co primary efficacy endpoints , and patients improved with or without sedation . Fewer than 1 % of patients in the carisoprodol 250-mg group discontinued prematurely because of treatment-emergent adverse events , and no patient discontinued because of drowsiness . Conclusions : When administered three times daily and at bedtime , carisoprodol 250 mg was as effective as 350 mg three times daily and at bedtime with a lower incidence of adverse events and fewer discontinuations of therapy due to adverse events . Patients improved whether or not they reported sedation as an adverse event OBJECTIVE To investigate the changes in 2 electromyographic measures , flexion relaxation ( FR ) response and feed-forward activation of the deep abdominals , associated with low back pain ( LBP ) after different rehabilitation interventions . DESIGN A 2x2 factorial design with subjects ' self- selecting treatment with r and omization after 4 weeks to either the specific exercise group or exercise advice group for a further 12-week period . SETTING General community practitioners and university training center . PARTICIPANTS Subjects with chronic nonspecific LBP were recruited for this study . A total of 112 people were initially screened , and 60 were recruited for the study , with 50 being available for long-term follow-up . INTERVENTION Four weeks of treatment ( manipulative or nonmanipulation ) and 12 weeks of subsequent exercise ( supervised Swiss ball training or exercise advice ) . MAIN OUTCOME MEASURES The Oswestry Disability Index , FR response measured at T12-L1 and L4 - 5 , and feed-forward activation of the deep abdominal muscles . RESULTS More rapid improvements in disability were identified for subjects who received the supervised exercise program . The FR response at L4 - 5 also increased more for those who received directly supervised exercise . Long-term follow-up showed that there was still a between-group difference in the FR response , despite no difference in self-rated disability . Long-term changes were observed for the feed-forward activation of the deep abdominals ; however , no exercise or treatment effects were identified . CONCLUSIONS Supervised exercise rehabilitation leads to more rapid improvements in self-rated disability , which were associated with greater improvement in the low back FR response Objectives Muscular pain is usually associated with increased muscle tension result ing in a vicious tension-pain-cycle , leading to increased alertness and stress . However , this has not been broadly evaluated using objective methods , for example , looking at neurophysiologic changes . The focus of this study was , therefore , to combine objective [ spontaneous electroencephalogram ( EEG ) as a surrogate of alertness and stress ] with subjective parameters ( self-assessed pain affected variables ) to investigate the effect of continuous low-level heat therapy in low back pain (LBP)- patients . Methods This investigation was a r and omized , active controlled , parallel- design ed study . Thirty patients were r and omly assigned to one of 2 groups : the control group , in which patients were provided with oral analgesics ( nonsteroidal anti-inflammatory drug ) and instructed to use it if needed , and the treatment group , in which patients in addition to oral analgesics as rescue medication were provided with a heatwrap therapy . The objective parameters were assessed by measuring the power of frequency b and s in the spontaneous EEG . The subjective parameters ( sleep pattern , well-being , pain intensity , etc . ) were assessed by a Pain , Sleep , and Stress Question naire . Results In the EEG-recordings , the heatwrap therapy group showed decreased power in Beta-1 and Beta-2 frequency b and s compared with the control group , indicating a reduction in arousal . Also , in comparison to the control group , the heatwrap therapy group reported significantly reduced LBP , everyday situations being less stressful , a better night 's sleep , and a decreased number of daytime naps . Discussion In addition to classic psychophysical assessment of pain-related parameters and sleep quality , performance in daily life , we were able to obtain objective measures ( EEG ) that suggest an acute therapeutic relaxation on the basis of the central nervous system effects accompanying the reported significant pain relief . We believe that this was due to a reduced nociceptive information load in LBP- patients after the use of the heatwrap therapy PURPOSE This panel-r and omized intervention trial was design ed to examine the effect of a motor control training program for elite Australian Football League players with and without low back pain ( LBP ) . METHODS The outcome measures included cross-sectional area ( CSA ) and symmetry of multifidus , quadratus lumborum , and psoas muscles and the change in CSA of the trunk in response to an abdominal drawing-in task . These measures of muscle size and function were performed using magnetic resonance imaging . Availability of players for competition games was used to assess the effect of the intervention on the occurrence of injuries . The motor control program involved performance of voluntary contractions of the multifidus and transversus abdominis muscles while receiving feedback from ultrasound imaging . Because all players were to receive the intervention , the trial was delivered as a stepped-wedge design with three treatment arms ( a 15-wk intervention , a 8-wk intervention , and a waitlist control who received a 7-wk intervention toward the end of the playing season ) . Players participated in a Pilates program when they were not receiving the intervention . RESULTS The intervention program was associated with an increase in multifidus muscle size relative to results in the control group . The program was also associated with an improved ability to draw-in the abdominal wall . Intervention was commensurate with an increase in availability for games and a high level of perceived benefit . CONCLUSIONS The motor control program delivered to elite footballers was effective , with demonstrated changes in the size and control of the targeted muscles . In this study , footballers who received the intervention early in the season missed fewer games because of injury than those who received it late in the playing season Low back pain ( LBP ) is a very common problem in primary care and a major cause of disability . There is no evidence for the efficacy of therapeutic modalities such as ultrasound in LBP In a r and omized , single blind placebo controlled clinical trial , we aim ed to evaluate the effect of continuous ultrasound ( US ) in patients with non specific LBP Of the fifty eight patients recruited , 10 patients ( 8 women and 2 men ) r and omly allocated to ultrasound ( n=5 ) or placebo controlled ( n=5 ) groups . The patients were treated by either US or sham-US for ten sessions , three days per week , every other day . The outcome measures were Functional Rating Index ( FRI ) , Hmax/Mmax ratio and range of motion ( ROM ) , which were measured at baseline , after 5 treatment sessions and at the end of treatment . To analyze the data , The Mann Whitney U test and Wilcoxon Signed Rank test were used . After treatment , both US and placebo groups showed statistically significant decrease in FRI scores indicating improvement in functional ability ( p = 0.042 and p = 0.043 , respectively ) . The mean changes of FRI during the second five treatment sessions and after the end of treatment was significantly better in the US group than in the placebo group ( p = 0.016 and p = 0.032 , respectively ) . Before and after treatment , the mean H reflex latency and Hmax/Mmax ratio , right and left side were similar in the groups ( p > 0.05 ) , and no significant changes were observed in the treatment groups ( p > 0.05 ) . After treatment , the extension and lateral flexion range of motion significantly increased in the US group ( p = 0.04 ) , but the back movements in the placebo group did not show significant changes ( p > 0.05 ) . The present study supports the significant effect of US on LBP , and suggests that US may improve the functional ability of patients with non specific low back pain BACKGROUND The goal of this study was to evaluate the efficacy of laser acupuncture for the clinical picture of chronic back pain under everyday conditions using a r and omized , double-blind , placebo-controlled study design . A further aim was to analyze to what extent placebo effects also influence the outcome of acupuncture under these conditions . PATIENTS AND METHODS The study included male and female patients with chronic back pain ( lasting longer than 6 months ) aged between 30 and 77 years with a pain score of at least 5 on a visual analog scale . The main criterion was achieving alleviation of pain by at least 50 % 3 months after the start of treatment . The assessment tools used were the Von Korff question naire supplemented by the FFbH , FABQ , and SF-12 . In addition , the participants were question ed about whether they perceived anything during the treatment and how certain they were that they had received treatment with active or inactive lasers . RESULTS A total of 111 patients were included in the study and were treated according to the r and omization list in two groups each consisting of 51 subjects . The study was completed as scheduled by 102 participants . Analysis of the primary outcome measure , improvement of the pain score by more than 50 % over baseline , revealed improvements in both treatment groups between the time points used for measurement . The placebo group exhibited better levels than the group that received laser treatment . No efficacy advantage of laser acupuncture over placebo treatment could be determined . CONCLUSION It was possible to completely blind the acupuncture forms with the study design employed . Perhaps the consistent exclusion of nonspecific treatment effects contributed to this result . It can not be ruled out that the effects of acupuncture are based on a strong placebo effect Study Design . The effectiveness and efficacy of Iyengar yoga for chronic low back pain ( CLBP ) were assessed with intention-to-treat and per- protocol analysis . Ninety subjects were r and omized to a yoga ( n = 43 ) or control group ( n = 47 ) receiving st and ard medical care . Participants were followed 6 months after completion of the intervention . Objective . This study aim ed to evaluate Iyengar yoga therapy on chronic low back pain . Yoga subjects were hypothesized to report greater reductions in functional disability , pain intensity , depression , and pain medication usage than controls . Summary of Background Data . CLBP is a musculoskeletal disorder with public health and economic impact . Pilot studies of yoga and back pain have reported significant changes in clinical ly important outcomes . Methods . Subjects were recruited through self-referral and health professional referrals according to explicit inclusion /exclusion criteria . Yoga subjects participated in 24 weeks of biweekly yoga classes design ed for CLBP . Outcomes were assessed at 12 ( midway ) , 24 ( immediately after ) , and 48 weeks ( 6-month follow-up ) after the start of the intervention using the Oswestry Disability Question naire , a Visual Analog Scale , the Beck Depression Inventory , and a pain medication-usage question naire . Results . Using intention-to-treat analysis with repeated measures ANOVA ( group × time ) , significantly greater reductions in functional disability and pain intensity were observed in the yoga group when compared to the control group at 24 weeks . A significantly greater proportion of yoga subjects also reported clinical improvements at both 12 and 24 weeks . In addition , depression was significantly lower in yoga subjects . Furthermore , while a reduction in pain medication occurred , this was comparable in both groups . When results were analyzed using per- protocol analysis , improvements were observed for all outcomes in the yoga group , including agreater trend for reduced pain medication usage . Although slightly less than at 24 weeks , the yoga group had statistically significant reductions in functional disability , pain intensity , and depression compared to st and ard medical care 6-months postintervention . Conclusion . Yoga improves functional disability , pain intensity , and depression in adults with CLBP . There was also a clinical ly important trend for the yoga group to reduce their pain medication usage compared to the control group BACKGROUND Duloxetine has demonstrated analgesic effect in chronic pain states . This study assesses the efficacy of duloxetine in chronic low back pain ( CLBP ) . METHODS Adult patients with non-radicular CLBP entered this 13-week , double-blind , r and omized study comparing duloxetine 20 , 60 or 120 mg once daily with placebo . The primary measure was comparison of duloxetine 60 mg with placebo on weekly mean 24-h average pain . Secondary measures included Rol and -Morris Disability Question naire ( RMDQ-24 ) , Patient 's Global Impressions of Improvement ( PGI-I ) , Brief Pain Inventory ( BPI ) , safety and tolerability . RESULTS Four hundred four patients were enrolled , 267 completed . No significant differences existed between any dose of duloxetine and placebo on reduction in weekly mean 24-h average pain at end-point . Duloxetine 60 mg was superior to placebo from weeks 3 - 11 in relieving pain , but not at weeks 12 - 13 . Duloxetine 60 mg demonstrated significant improvement on PGI-I , RMDQ-24 , BPI-average pain and BPI-average interference . Significantly more patients taking duloxetine 120 mg ( 24.1 % ) discontinued because of adverse events , versus placebo ( 8.5 % ) . CONCLUSIONS Duloxetine was superior to placebo on the primary objective from weeks 3 - 11 , but superiority was not maintained at end-point . Duloxetine was superior to placebo on many secondary measures , and was well-tolerated Objective : To compare the effectiveness of an isokinetic exercise programme and a st and ard exercise programme in patients with chronic low back pain in terms of pain , mobility , disability , psychological status and muscle strength . Design : A r and omized controlled trial . Setting : An outpatient rehabilitation clinic . Subjects : A total of 40 patients with low back pain were included in the study . Interventions : Patients with low back pain were r and omly allocated into group 1 ( n=20 , isokinetic exercises ) and group 2 ( n=20 , st and ard exercise ) . Main measures : Outcome measures included a visual analogue scale ( VAS ) for pain , fingertip-to-floor test for spinal mobility , Modified Oswestry Low Back Disability Question naire ( MOLBDQ ) , Beck Depression Inventory and isokinetic muscle testing . Results : The isokinetic and st and ard exercise groups demonstrated significant improvement in the VAS , fingertip-to-floor test , MOLBDQ , Beck Depression Inventory scores , and muscle strength compared with the baseline that persisted until the end of the first month ( P<0.05 ) . Comparison of both exercise groups in terms of these parameters obtained at the end of the treatment and at the first month after treatment showed no significant difference ( P>0.05 ) . Conclusion : Isokinetic and st and ard exercise programmes have an equal effect in the treatment of low back pain , with no statistically significant difference found between the two programmes . The st and ard exercise programme was easily performed and had a low cost , making it the preferred option for exercise & NA ; The present study tested a short intervention using goal ‐pursuit strategies to increase physical capacity in pain patients . Sixty chronic back pain patients were r and omly assigned to intervention or control conditions . Both groups followed a 3‐week conventional back pain program at an outpatient back pain center . Instead of routine treatment , the intervention group received a one‐hour intervention consisting of a combination of ( a ) a goal ‐ setting strategy ( i.e. , mental contrasting , MC ) aim ed at commitment to improved physical capacity , ( b ) a short cognitive behavioral therapy‐oriented problem‐solving approach ( CBT ) to help patients overcome the obstacles associated with improving physical capacity , and ( c ) a goal ‐pursuit strategy , i.e. , implementation intentions ( II ) aim ed at performing physical exercise regularly . At two follow‐ups ( 3 weeks after discharge and 3 months after returning home ) the MCII‐CBT group had increased its physical capacity significantly more than the control group as measured by both behavioral measures ( ergometer , lifting ) and subjective ratings . Findings are discussed with relation to the use of the intervention as a specific treatment to increase chronic pain patients ’ motivation to be physically active |
1,667 | 23,116,501 | Currently , no evidence indicates that specific maximum insertion torque levels are associated with higher success rates for orthodontic mini-implants . | INTRODUCTION In this systematic review , we analyzed whether recommended maximum insertion torque values of 5 to 10 Ncm were associated with higher success rates of orthodontic mini-implants compared with mini-implants inserted with maximum insertion torque values beyond this range .
Objective assessment s of stability , variables that influence maximum insertion torque values , and adverse effect of interventions were also assessed in the studies selected for our PICO ( patient problem or population , intervention , comparison , and outcomes ) question . | INTRODUCTION The purpose s of the study were to evaluate the immediate damage to roots and periodontal structures after initial miniscrew implant ( MSI ) placement and the short- and long-term damage after MSIs were left in situ . METHODS The roots of the maxillary second , third , and fourth premolars of 7 mature beagle dogs were r and omly assigned to undergo immediate , short-term ( left for 6 weeks ) , or long-term ( left for 12 weeks ) damage . Intentional damage was inflicted with self-tapping screws ( 1.8 x 8 mm ) placed with a stent . Alternating tetracycline and calcein labels were administered at 6-week intervals . Undecalcified sections were stained and evaluated histologically to determine the extent of damage ; healing was evaluated by using fluorescence labels . RESULTS Histology showed damage to 73.8 % of the teeth , ranging from displacement of bone into the periodontal ligament to invasion of the pulp chamber . Displacement of bone into the periodontal ligament and direct damage to the periodontal ligament occurred in 3 ( 7.2 % ) instances . Damage was isolated to the cementum of 8 ( 19.0 % ) teeth , whereas damage occurred in the dentin of 11 ( 26.2 % ) teeth . Loss of bone in the furcation was evident in 3 ( 7.2 % ) teeth , and severe damage into the pulp occurred in 6 ( 14.2 % ) teeth . No differences in the amounts of damage were evident between the immediate , short- , and long-term groups . Healing often occurred with cementum around the unloaded MSIs . CONCLUSIONS Extensive damage can be caused by MSIs , with little to no differences evident over time . Unloaded MSIs that remain in contact with roots of teeth can show varying degrees of healing PURPOSE The aim of this prospect i ve clinical study was to assess the risk factors associated with failure of mini-implants used for orthodontic anchorage . MATERIAL S AND METHODS A total of 140 mini-implants in 44 patients , including 48 miniplates and 92 freest and ing miniscrews , were examined in the study . A variety of orthodontic loads were applied . The majority of implants were placed in the posterior maxilla ( 104/140 ) , and the next most common location was the posterior m and ible ( 34/140 ) . RESULTS A cumulative survival rate of 89 % ( 125/140 ) was found by Kaplan-Meier analysis . There was no significant difference in the survival rate between miniplates and freest and ing miniscrews , but miniplates were used in more hazardous situations . The Cox proportional-hazards regression model identified anatomic location and peri-implant soft tissue character as 2 independent prognostic indicators . The estimated relative risk of implant failure in the posterior m and ible was 1.101 ( 95 % confidence interval , 0.942 to 1.301 ; P = .046 ) . The risk ratio of failure for implants surrounded by nonkeratinized mucosa was 1.117 ( 95 % confidence interval , 0.899 to 1.405 ; P = .026 ) . DISCUSSION AND CONCLUSION The results confirmed the effectiveness of orthodontic mini-implants , but in certain situations adjustment of the treatment plan or modifications in the technique of implant placement may lead to improved success rates INTRODUCTION The purpose of this study was to investigate the effects of the diameter and shape of orthodontic mini-implants ( OMIs ) on microdamage to the cortical bone during implant placement . METHODS Twenty-eight self-drilling OMIs ( Bio material s Korea , Seoul , Korea ; length , 6 mm ; diameters , 1.5 and 2 mm ; cylindrical and tapered shapes ; classified as 1.5C , 2C , 1.5 T , and 2 T ) were placed with a surgical device in the tibias of 7 New Zeal and white rabbits ( mature males ; mean age , 6 months ; mean weight , 3.1 kg ) . Four OMIs of each type per rabbit were placed r and omly . Maximum insertion torque ( MIT ) was measured . Immediately after placement of the OMIs , the block of bone with the OMI was harvested . Cortical bone thickness was measured by using microcomputed tomography , and histomorphometric analyses of the number of cracks ( NC ) , accumulated crack length ( ACL ) , maximum radius of the crack ( MRC ) , and longest crack ( LC ) were performed . Kruskal-Wallis and Mann-Whitney U tests with the Bonferroni adjustment were done for statistical analyses . RESULTS Increased diameter ( 1.5C<2C and 1.5T<2 T ) and tapering ( 1.5C<2 T ) result ed in increased values of MIT , NC , and LC ( P < 0.01 , respectively ) . Similarly , with increased diameters ( 1.5C and 1.5T<2C and 2 T ) , there were increases of ACL and MRC ( P < 0.001 , respectively ) . However , there were no differences in the values of MIT , NC , ACL , MRC , and LC between the cylindrical and tapered OMIs with the same diameters ( 1.5C and 1.5 T , 2C and 2 T ) . CONCLUSIONS OMIs with larger diameters and tapered shapes caused greater microdamage to the cortical bone ; this might affect bone remodeling and the stability of the OMIs PURPOSE This study evaluated the survival parameters of single-tooth implants through clinical and radiographic analysis . MATERIAL S AND METHODS Implants were restored within a 24-hour period with a provisional crown design ed to receive an occlusal masticatory load . This approach was compared to implants restored after a healing period ( the control group ) . Forty-six implants were placed in 23 patients who were each treated with 2 Frialit-2 implants placed in sites between the second premolar in the maxilla or m and ible . The manufacturer 's recommended formal surgical procedure was followed , and primary stability was st and ardized with a minimum insertion torque of 20 Ncm . The sites were r and omly selected , and the clinical and radiographic parameters were st and ardized with individual templates . RESULTS Data were collected at 24 h , and at 1 , 3 , 6 , 12 , 18 , and 24 months . The experimental group included 10 failed implants ; 9 of the failed implants had been placed with an insertion torque of 20 Ncm . One implant from the control group failed during the 24-month follow-up period . The survival rate was independent of implant length , site position , and bone quality and quantity . Relative risk for implant failure was associated with insertion torque ( relative risk 0.79 [ CI : 0.66 - 0.930 ] ; Cox regression ) ( P < or = .007 ) , in the experimental group but was not significant for those in the control group ( ie , implants placed after a healing period ; relative risk 0.78 [ CI : 0.34 - 1.78 ] ; Cox regression ) ( P < or = .057 ) . To achieve osseointegration , it was found that an insertion torque above 32 Ncm was necessary ( chi2= 15.68 ; P < or = .004 ) . DISCUSSION A careful evaluation is necessary for a better underst and ing of the survival rates of immediately loaded implants . In this study , insertion torque was associated with the potential for risk , which can be decreased by 20 % per 9.8 Ncm added . CONCLUSION Given these results , and considering the number of patients treated , immediate provisional crowns should only be proposed with early loading if an appropriate initial insertion torque has been applied INTRODUCTION We compared the stability of 3- and 6-mm long miniscrew implants ( MSIs ) loaded with orthopedic force levels . METHODS Using a split-mouth experimental design , we placed MSIs into the jaws of 5 mature beagle dogs and immediately loaded them for 6 weeks . Continuous forces were applied by reciprocally loading pairs of MSIs with nickel-titanium coil springs . The m and ibles had the 3-mm MSIs r and omly loaded with forces of 600 or 900 g. In the maxilla , the 3- and 6-mm MSIs were r and omly assigned and loaded with 600 g of force . An unloaded , control MSI was placed in each quadrant . Overall success was defined as MSIs that remained intact ; net success rates excluded MSIs that had sheared off and all implants placed in a dog that frequently chewed his run bars and food bowl . RESULTS The overall success rates of the loaded and the control 6-mm MSIs were 100 % . Overall and net success rates for the 3-mm experimental MSIs were 66.7 % and 95.2 % , respectively . Similarly , the overall and net success rates of the 3-mm control MSIs were 66.7 % and 81.8 % , respectively . The overall success rates of the 3-mm m and ibular MSIs loaded with 900 and 600 g of force were both 60 % ; their net success rates were 100 % with 900 g and 85.7 % with 600 g. Overall success rates of the 3-mm experimental MSIs in the maxilla and the m and ible were 80 % and 60 % , repectively . The net success rates were 100 % ( maxilla ) and 85.7 % ( m and ible ) . There were no significant ( P > 0.05 ) differences in stability associated with force or location . The loaded 3- and 6-mm MSI pairs demonstrated significant decreases in interimplant distance , averaging 2.2 and 1.8 mm , respectively ; the 3-mm MSIs loaded with 900 g showed significantly more displacement than those loaded with 600 g. CONCLUSIONS Success rates of immediately loaded 3-mm MSIs were significantly lower than those of immediately loaded 6-mm MSIs . Neither force nor location explained differences in the success rates . The linear displacements of the MSIs were associated with load amount rather than implant length Miniscrews have been used in recent years for anchorage in orthodontic treatment . However , it is not clear whether the miniscrews are absolutely stationary or move when force is applied . Sixteen adult patients with miniscrews ( diameter = 2 mm , length = 17 mm ) as the maxillary anchorage were included in this study . Miniscrews were inserted on the maxillary zygomatic buttress as a direct anchorage for en masse anterior retraction . Nickel-titanium closed-coil springs were placed for the retraction 2 weeks after insertion of the miniscrews . Cephalometric radiographs were taken immediately before force application ( T1 ) and 9 months later ( T2 ) . The cephalometric tracings at T1 and T2 were superimposed for the overall best fit on the structures of the maxilla , cranial base , and cranial vault to determine any movement of the miniscrews . The miniscrews were also evaluated clinical ly for their mobility ( 0 : no movement , 1 : < or = 0.5 mm , 2 : 0.5 - 1.0 mm , 3 : > 1.0 mm ) . The mobility of all miniscrews was 0 at T1 and T2 . On average , the miniscrews tipped forward significantly , by 0.4 mm at the screw head . The miniscrews were extruded and tipped forward ( -1.0 to 1.5 mm ) in 7 of the 16 patients . Miniscrews are a stable anchorage but do not remain absolutely stationary throughout orthodontic loading . They might move according to the orthodontic loading in some patients . To prevent miniscrews hitting any vital organs because of displacement , it is recommended that they be placed in a non-tooth-bearing area that has no foramen , major nerves , or blood vessel pathways , or in a tooth-bearing area allowing 2 mm of safety clearance between the miniscrew and dental root The possibility of using osseointegrated implants for orthodontic anchorage is well known . When absolute orthodontic anchorage is needed , mini-implants can be inserted in the non-alveolar bone area ( e.g. palatal process or retromolar areas of the m and ible ) . However , what happens to these implants at the end of treatment can be a problem as neither trephine explantation nor simply leaving the subgingival part of the implant in the bone permanently are acceptable solutions . In this investigation , 16 Exacta small screw titanium implants ( Exacta MS series conical profile , with a diameter of 3.3 mm and a length of 7.0 mm ) were used as indirect orthodontic anchorage in 16 adult patients . The site of implant placement was established based on radiological investigations . There were eight palatal and eight retromolar implants inserted in seven males and nine females ( mean age 30.3 years ) . On completion of treatment , the implants were unscrewed to the maximum limits of their removal torque values ( RTVs ) and the obtained data were analysed using a t-test . An in vitro study before the clinical trial was also undertaken to determine the maximum mechanical resistance of the unscrewing system . The clinical procedure and average RTV ( 67.91 + /- 12.47 N/cm ) were considered compatible with safe , non-invasive removal of the implant followed by rapid anatomical reconstruction of the area involved OBJECTIVE To test the hypothesis that there is no difference in the stability and resistance to rotational moments of early loaded s and blasted and acid-etched ( SLA ) mini-implants and those of machined-surface implants of the same size and shape . MATERIAL S AND METHODS A r and omized complete block design was used in 12 skeletally mature male beagle dogs . Ninety-six orthodontic mini-implants were tested . Two types of implants were used : some had SLA surface treatment and some had machined surfaces without coating . After 3 weeks of healing , rotational moments of 150 g were applied . The success rates , maximum torque values , angular momentum , and total energy absorbed by the bone were compared . All values were subjected to mixed-model analysis to evaluate the influence of surface treatment , rotational force direction , and site of implantation . RESULTS The maximum insertion torque and angular momentum of SLA implants were significantly lower than those of machined implants ( P = .034 , P = .039 ) . The SLA implants had a significantly higher value for total removal energy than the machined implants ( P = .046 ) . However , there were no significant differences in total insertion energy , maximum removal torque , and removal angular momentum between the 2 groups . There was no significant difference between clockwise and counterclockwise rotation in all measurements . CONCLUSION SLA mini-implants showed relatively lower insertion torque value and angular momentum and higher total energy during removal than the machined implants , suggesting osseointegration of the SLA mini-implant after insertion In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies INTRODUCTION The purpose of this study was to investigate the success rate of midpalatal miniscrews used for orthodontic anchorage and the factors affecting clinical success . METHODS One hundred twenty-eight consecutive patients ( 101 female , 27 male ; mean age , 23.4 years ) , who received a total of 210 miniscrews in the midpalatal suture area , were examined . Success rates were determined according to 10 clinical variables . RESULTS The overall success rates were 88.20 % for the total number of patients and 90.80 % for the total number of miniscrews . There were no significant associations among success rate and sex , total period of treatment with miniscrews , diameter of miniscrews , types of tooth movements , and variables that represent sagittal and vertical skeletal relationships ( ANB , FMA , and Sn-GoGn ) . The operator 's learning curve , patient 's age , area ( midpalatal or parapalatal ) , and splinting significantly influenced the success rates . After adjusting for other variables , only 1- splinting-showed a significant effect on the success rate . CONCLUSIONS The joining of 2 miniscrews by splinting , placement of the miniscrew in the midpalatal suture , patient 's age ( especially > 15 years ) , and operator 's skill were factors influencing the clinical success of orthodontic miniscrews in the palate AIM The purpose of this investigation was to determine and compare the accuracy of four available mechanical torque-limiting gauges ( MTLGs ) for mini-screw placement . MATERIAL S AND METHODS The torque outputs of six r and omly obtained MTLGs , either of the screwdriver or torque ratchet type of four mini-screw manufacturers were obtained . Mounted on a joint , a universal testing machine applied perpendicular force to a lever arm with a crosshead speed of 1 mm/min . For each device , 10 repetitions of the corresponding target torque level were recorded after initial sterilisation ( 1 ) and after 5 , 10 , 20 , 50 and 100 times to evaluate its potential influence on MTLGs . The breakpoints ( N cm ) were calculated for comparison of the groups . Descriptive statistics and mean breakpoints values for each MTLG computed and compared with the reference values indicated on the respective torque gauges provided by the producer . RESULTS The mean torque values for the AbsoAnchor MTLG devices were significantly below torque levels , but provide consistent torque values . All but one obtained values for the Spider Screw , MTLG of the screw driver type , were within the indicated moment range during the first 50-times of sterilization process . But after 100-times of steam sterilization all mean breakpoint values were relevantly higher than the indicated torque range values . Each individual MTLG produced independently constant breakpoint torque values , but differed significantly from each other . For all but the Spider Screw MTLG , the sterilisation process had a statistically significant different influence at the various breakpoint torque levels . CONCLUSION After application of the manufacturers ' preset torque levels , significant variations were observed between individual devices . The torque output of each individual device deviated in varying degrees from target torque values and was influenced by various degrees by the sterilisation process over time |
1,668 | 29,157,151 | The majority of studies reported positive effects result ing from hard martial arts practice , showing some improvement and maintenance of balance , cognitive function and psychological health .
Benefits may be obtained regardless of the age of practice commencement .
“ Hard ” martial arts seem to have potential to improve balance and cognitive functions that decline with age , which can lead to poorer health outcomes among the elderly ( e.g. cognitive decline , falls and fractures ) . | ABSTRACT Participation in organized sports is promoted as a means of increasing physical activity levels and reducing chronic disease risk in adults .
Hard martial arts practice ( i.e. using body contact techniques ) , has gained in popularity over time .
This review explores the evidence for health benefits of “ hard ” martial arts practice within the adult population . | Abstract Cognitive performance includes the processes of attention , memory , processing speed , and executive functioning , which typically declines with aging . Previous research has demonstrated that aerobic and resistance exercise improves cognitive performance immediately following exercise . However , there is limited research examining the effect that a cognitively complex exercise such as martial art training has on these cognitive processes . Our study compared the acute effects of 2 types of martial art training to aerobic exercise on cognitive performance in middle-aged adults . We utilized a repeated measures design with the order of the 3 exercise conditions r and omly assigned and counterbalanced . Ten recreational middle-aged martial artists ( mean age = 53.5 ± 8.6 years ) participated in 3 treatment conditions : a typical martial art class , an atypical martial art class , and a one-hour walk at a self-selected speed . Cognitive performance was assessed by the Stroop Color and Word test . While all 3 exercise conditions improved attention and processing speed , only the 2 martial art conditions improved the highest order of cognitive performance , executive function . The effect of the 2 martial art conditions on executive function was not different . The improvement in executive function may be due to the increased cortical dem and required by the more complex , coordinated motor tasks of martial art exercise compared to the more repetitive actions of walking Injuries can be an adverse outcome of participation in sport and recreational activities . The aim of this study was to determine the public health impact of injury during sports and active recreation injury in a select population in Australia . A r and om household telephone survey was conducted quarterly over a 12-month period in a well-defined geographic region , the Latrobe Valley , Australia . Information was collected on participation in sport and active recreation and associated injuries over the previous 2 weeks for all household members aged over 4 years . Injury rates were calculated per 10,000 population and per 1000 sports participants . Data were collected on 1084 persons from 417 households . Overall , 648 people reported participating in at least one sport or active recreation and 34 ( 5.2 % , 95 % CI : 4.8 , 5.6 % ) of these sustained an injury during this activity . Overall , 51.4 % of injured cases had a significant impact : 26.5 % sought treatment , 34.4 % had their activities of daily living adversely affected and 36.0 % had their performance/participation limited . Cricket ( 51 injuries/10,000 population ) , horse riding ( 29/10,000 population ) and basketball ( 25/10,000 population ) had the highest injury rates . After adjusting for participation , cricket ( 242 injuries/1000 participants ) , horse riding ( 122/1000 participants ) and soccer ( 107/1000 participants ) had the highest injury rates . Cricket and soccer were the sports most associated with ' significant ' injuries . Injury prevention efforts should be aim ed at team ball sports ( especially cricket , soccer and netball ) because of their comparatively high rate of both overall and ' significant ' injury [ Purpose ] The aim of this study was to investigate the effects of Ving Tsun ( VT ) Chinese martial art training on radial bone strength , upper- and lower-limb muscular strength , shoulder joint mobility , balance performance , and self-efficacy in elderly participants . [ Subjects and Methods ] Twelve seniors voluntarily joined the VT training group , and twenty-seven seniors voluntarily joined the control group . The VT group received VT training for three months , while the control group received no training . The bone strength of the distal radius was assessed using an ultrasound bone sonometer . Muscular strength in the limbs was evaluated using a Jamar h and grip dynamometer and the five times sit-to-st and test . Shoulder joint mobility was examined using a goniometer . Balance performance and self-efficacy were evaluated using the Berg Balance Scale and the Chinese version of the Activities-specific Balance Confidence Scale , respectively . [ Results ] The results revealed a nonsignificant group-by-time interaction effect , group effect , and time effect for all outcome variables . However , general trends of maintenance or improvement in all outcome parameters were observed to a greater extent in the VT group than in the control group . [ Conclusion ] VT training might be a potential fall-prevention exercise that can be used to maintain general physique , balance , and confidence in the elderly population . A further r and omized controlled trial is needed to confirm this postulation AIM the purpose of this study was to examine the effect of kickboxing training on physical fitness . METHODS 30 subjects were r and omized into a kickboxing-group ( n=15 ) and control group ( n=15 ) . Each group trained approximately 1-hour per day , three-times per a week during five weeks . Muscle-power ( upper-body : bench-press-test , medicine-ball-test ; lower-body : squat-jump and counter-movement-jump-test ) , flexibility , speed and agility , aerobic ( progressive maximal exercise test ) , anaerobic fitness ( Wingate test ) and body composition were assessed before and after the training period . RESULTS the kickboxing group showed significant improvement ( p < 0.05 ) in upper-body muscle power , aerobic power , anaerobic fitness , flexibility , speed and agility after training whereas body composition , squat jump and counter movement jump ( height , power and velocity components ) did not change for both groups . CONCLUSION kickboxing- practice was effective to change many physical variables . Thus , this activity can be useful for enhancing physical fitness , but complementary activities and /or nutritional interventions should be necessary Objective : To investigate the epidemiology of sports and recreation-related injury ( SRI ) among emergency department ( ED ) attendees . Design : Descriptive epidemiology study . Setting : An Irish university hospital ED . Participants : All patients aged over 4 years attending a large regional ED , during a 6-month period , for the treatment of SRI were prospect ively surveyed . Assessment of Risk Factors : In all cases identified as SRI the attending physician completed a specifically design ed question naire . It was postulated that recreation-related injury is a significant proportion of reported SRI . Results : Fracture rate was highest in the 4–9-year age group ( 44 % ) . On multivariate logistic regression the adjusted odds ratio ( OR ; 95 % CI ) of fracture was higher for children ( vs adults ) at 1.21 ( 1.0 to 1.45 ) . The adjusted OR was higher for upper-limb 5.8 ( 4.5 to 7.6 ) and lower-limb injuries 1.87 ( 1.4 to 2.5 ) versus axial site of injury and for falls 2.2 ( 1.6 to 2.9 ) and external force 1.59 ( 1.2 to 2.1 ) versus an overextension mechanism of injury . In the same model , “ play ” was independently associated with fracture risk , adjusted OR 1.98 ( 1.2 to 3.0 ; p = 0.001 ) versus low-risk ball sports 1.0 ( reference ) ; an effect size similar to that seen for combat sports 1.96 ( 1.2 to 3.3 ; p = 0.01 ) and greater than that seen for presumed high-risk field sports 1.4 ( 0.9 to 2.0 ) Conclusion : Fall and subsequent upper-limb injury was the commonest mechanism underlying SRI fracture . Domestic “ play ” in all age groups at the time of injury accorded a higher fracture risk than field sports . Patient education regarding the dangers of unsupervised play and recreation represents a means of reducing the burden of SRI IMPORTANCE Few studies have examined how different proportions of moderate and vigorous physical activity affect health outcomes . OBJECTIVE To examine whether the proportion of total moderate to vigorous activity ( MVPA ) that is achieved through vigorous activity is associated with all-cause mortality independently of the total amount of MVPA . DESIGN , SETTING , AND PARTICIPANTS We performed a prospect i ve cohort study with activity data linked to all-cause mortality data from February 1 , 2006 , through June 15 , 2014 , in 204,542 adults aged 45 through 75 years from the 45 and Up population -based cohort study from New South Wales , Australia ( mean [ SD ] follow-up , 6.52 [ 1.23 ] years ) . Associations between different contributions of vigorous activity to total MVPA and mortality were examined using Cox proportional hazards models , adjusted for total MVPA and sociodemographic and health covariates . EXPOSURES Different proportions of total MVPA as vigorous activity . Physical activity was measured with the Active Australia Survey . MAIN OUTCOMES AND MEASURES All-cause mortality during the follow-up period . RESULTS During 1,444,927 person-years of follow-up , 7435 deaths were registered . Compared with those who reported no MVPA ( crude death rate , 8.34 % ) , the adjusted hazard ratios for all-cause mortality were 0.66 ( 95 % CI , 0.61 - 0.71 ; crude death rate , 4.81 % ) , 0.53 ( 95 % CI , 0.48 - 0.57 ; crude death rate , 3.17 % ) , and 0.46 ( 95 % CI , 0.43 - 0.49 ; crude death rate , 2.64 % ) for reporting 10 through 149 , 150 through 299 , and 300 min/wk or more of activity , respectively . Among those who reported any MVPA , the proportion of vigorous activity revealed an inverse dose-response relationship with all-cause mortality : compared with those reporting no vigorous activity ( crude death rate , 3.84 % ) the fully adjusted hazard ratio was 0.91 ( 95 % CI , 0.84 - 0.98 ; crude death rate , 2.35 % ) in those who reported some vigorous activity ( but < 30 % of total activity ) and 0.87 ( 95 % CI , 0.81 - 0.93 ; crude death rate , 2.08 % ) among those who reported 30 % or more of activity as vigorous . These associations were consistent in men and women , across categories of body mass index and volume of MVPA , and in those with and without existing cardiovascular disease or diabetes mellitus . CONCLUSIONS AND RELEVANCE Among people reporting any activity , there was an inverse dose-response relationship between proportion of vigorous activity and mortality . Our findings suggest that vigorous activities should be endorsed in clinical and public health activity guidelines to maximize the population benefits of physical activity BACKGROUND Given the evidence that regular physical activity produces substantial health benefits , participation in sports , exercise , and recreation is widely encouraged . The objective of this study was to describe participation in sports , exercise , and recreational physical activities among US adults . METHODS Data from 2 national surveys of respondents age 18 years and older were analyzed . Respondents to the American Time Use Survey ( ATUS ) from 2003 through 2005 ( N=45,246 ) reported all activities on 1 r and omly selected survey day . Respondents to the National Health and Nutrition Examination Survey ( NHANES ) from 1999 through 2004 ( N=17,061 ) reported leisure-time physical activities in the 30 days before the interview . RESULTS One-quarter of adults participated in any sport , exercise , or recreational activity on a r and om day , and 60.9 % of adults participated in any leisure-time activity in the previous 30 days . The most common types of activities were walking , gardening and yard work , and other forms of exercise . The sports and recreational activities had typical duration s of 1/2 to 3 hours per session , and the exercise activities typically lasted 1 hour or less . CONCLUSIONS The prevalence of sports , exercise , and recreational physical activities is generally low among US adults ; exercise is the most commonly reported type of activity BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application Self-reported rates of participation in sport vary by country . In the UK , about 40 % of men and women aged 16 years or older participate in at least one sport every week . Although few data exist to assess trends for participation in sport , there is little evidence of change in the past decade among adults . Large cohort studies suggest that such participation in sport is associated with a 20 - 40 % reduction in all-cause mortality compared with non-participation . R and omised trials and crossover clinical studies suggest that playing sport is associated with specific health benefits . Some sports have relatively high injury risk although neuromuscular training programmes can prevent various lower extremity injuries . Clinicians can influence a large number of patients through brief interventions that promote physical activity , and encouragement toward participation in sport for some physically inactive patients qualifies as evidence -based therapy . Exercise might also be considered as a fifth vital sign and should be recorded in patients ' electronic medical records and routine histories Sports training , especially for those requiring fast and skilled movements have been reported to improve one ’s postural control , but the underlying sensory integration mechanism is unknown . The purpose is to explore the sensory organisation strategies for maintaining st and ing balance in Taekwondo practitioners , and to examine the quasi-static and dynamic balance performance in subjects with and without TKD training . Case – control study was used as a study design . Eleven subjects with low level of Taekwondo training for 1–3 years , and eleven sedentary healthy subjects were assessed with the sensory organisation tests ( SOT ) under six visual and somatosensory input conditions and their balance upon l and ing from self- or operator-triggered drop test with the eyes closed condition . The SOT measured the equilibrium scores , whereas the drop test assessed the time to stabilisation ( TTS ) , normalised peak force and distance of antero-posterior and medial – lateral centre of pressure on l and ing . Results for the SOT test revealed that Taekwondo subjects performed better during stance with eyes closed on a fixed support than the untrained group ( p = 0.011 ) . For the drop tests , the untrained group was slower in postural correction as revealed by the longer TTS than the Taekwondo group after the operator-triggered drops ( p = 0.018 ) . All subjects had a larger normalised peak force in operator-triggered than self-triggered drops . In conclusion , we observed that people with low-level Taekwondo training have better balance performance than untrained subjects as shown in the SOT results and shorter TTS with the drop test . They may rely more on the somatosensory and vestibular inputs for maintaining balance . People with balance problems may benefit from Taekwondo training |
1,669 | 21,198,407 | Exercises were also shown to be effective in reducing brace prescription .
This study ( like the previously published systematic review s ) showed that PEs can improve the Cobb angles of individuals with AIS and can improve strength , mobility , and balance . | Our goal was to verify if treatment with specific exercises for AIS has changed in these years . | Objectives : Physiotherapy programmes so far mainly address the lateral deformity of scoliosis , a few aim at the correction of rotation and only very few address the sagittal profile . Meanwhile , there is evidence that correction forces applied in the sagittal plane are also able to correct the scoliotic deformity in the coronal and frontal planes . So it should be possible to improve excellence in scoliosis rehabilitation by the implementation of exercises to correct the sagittal deformity in scoliosis patients . An exercise programme ( physio-logic ® exercises ) aim ing at a physiologic sagittal profile was developed to add to the programme applied at the centre or to replace certain exercises or exercising positions . Material and methods : To test the hypothesis that physio-logic ® exercises improve the outcome of Scoliosis Intensive Rehabilitation ( SIR ) , the following study design was chosen : Prospect i ve controlled trial of pairs of patients with idiopathic scoliosis matched by sex , age , Cobb angle and curve pattern . There were 18 patients in the treatment group ( SIR + physio-logic ® exercises ) and 18 patients in the control group ( SIR only ) , all in matched pairs . Average Cobb angle in the treatment group was 34.5 ° ( SD 7.8 ) Cobb angle in the control group was 31.6 ° ( SD 5.8 ) . Age in the treatment group was at average 15.3 years ( SD 1.1 ) and in the control group 14.7 years ( SD 1.3 ) . Thirteen of the 18 patients in either group had a brace . Outcome parameter : average lateral deviation ( mm ) , average surface rotation ( ° ) and maximum Kyphosis angle ( ° ) as evaluated with the help of surface topography ( Formetric ® -system ) . Results : Lateral deviation ( mm ) decreased significantly after the performance of the physio-logic ® programme and highly significantly in the physio-logic ® ADL posture ; however , it was not significant after completion of the whole rehabilitation programme ( 2.3 vs 0.3 mm in the controls ) . Surface rotation improved at average 1.2 ° in the treatment group and 0.8 ° in the controls while Kyphosis angle did not improve in both groups . Discussion : The physio-logic ® programme has to be regarded as a useful ‘ add on ’ to Scoliosis Rehabilitation with regards to the lateral deviation of the scoliotic trunk . A longitudinal controlled study is necessary to evaluate the long-term effect of the the physio-logic ® programme also with the help of X-rays UNLABELLED The Lyon school has proposed a preparation to brace wearing through an intensive mobilization in order to obtain a better reduction of the braced scoliotic curve . Our aim was to verify this hypothesis . DESIGN A prospect i ve controlled study on consecutive patients having idiopathic scoliosis with brace management . OUTCOME Results after 5 months of brace wearing were review ed by radiographic examination without the brace . TREATMENT SEAS Group exercises according to the protocol SEAS.02 ( Scientific Exercises Approach to Scoliosis , version 2002 ) ; CONT Group various type of exercises . Population . 110 patients ( 34 females ) , 13.5+/-2.4 years , 31.1 degrees + /-11.1 degrees Cobb ( degrees C ) , 14.4 degrees + /-6.0 degrees Bunnell ( degrees B ) . All parameters improved at follow-up in both groups . SEAS had better results than CONT for degrees C. Clinical results ( variations of at least 5 degrees C and 2 degrees B ) were better in SEAS than CONT . This study proves the efficacy of SEAS.02 exercises preparatory for bracing . Bracing demonstrated its short term efficacy The goal of this study is to test the hypothesis that physiotherapy-based intervention can reduce incidence of progression in children with IS . Two independent patient groups matched by age and sex at diagnosis were analysed using the outcome parameter , incidence of progression ( S 5 ° ) . One group was untreated and the other received scoliosis in-patient rehabilitation ( SIR ) . Incidence of progression in groups of untreated patients ranged from 1.5-fold ( 71.2 % vs 46.7 % ) to 2.9-fold ( 55.8 % vs 19.2 % ) higher than in groups of patients treated with SIR , even when SIR-treated groups included patients with more severe curvatures . Statistically , the differences were highly significant . Efforts to test the hypothesis that physical therapies addressing postural imbalance can be used effectively in the treatment of IS have been limited . The results of this study are consistent with the possibility that a supervized programme of exercise-based therapies can reduce incidence of progression in children with IS In a prospect i ve study by the Scoliosis Research Society , 286 girls who had adolescent idiopathic scoliosis , a thoracic or thoracolumbar curve of 25 to 35 degrees , and a mean age of twelve years and seven months ( range , ten to fifteen years ) were followed to determine the effect of treatment with observation only ( 129 patients ) , an underarm plastic brace ( 111 patients ) , and nighttime surface electrical stimulation ( forty-six patients ) . Thirty-nine patients were lost to follow-up , leaving 247 ( 86 per cent ) who were followed until maturity or who were dropped from the study because of failure of the assigned treatment . The end point of failure of treatment was defined as an increase in the curve of at least 6 degrees , from the time of the first roentgenogram , on two consecutive roentgenograms . As determined with use of this end point , treatment with a brace failed in seventeen of the 111 patients ; observation only , in fifty-eight of the 129 patients ; and electrical stimulation , in twenty-two of the forty-six patients . According to survivorship analysis , treatment with a brace was associated with a success rate of 74 per cent ( 95 per cent confidence interval , 52 to 84 ) at four years ; observation only , with a success rate of 34 per cent ( 95 per cent confidence interval , 16 to 49 ) ; and electrical stimulation , with a success rate of 33 per cent ( 95 per cent confidence interval , 12 to 60 ) . ( ABSTRACT TRUNCATED AT 250 WORDS UNLABELLED A new ADL ( Activities of Daily Living ) approach in scoliosis rehabilitation has been design ed . The ADL approach uses Side-Shift , physiologic(R ) , 3D-ADL exercises and Schroth exercises according to current st and ard . It was compared to an exercise based scoliosis rehabilitation that mainly uses Schroth exercises and as an add-on the training of ADL . The ADL approach in practice seems to be easier to teach and the treatment needs fewer theoretical modules leading to a better time-efficiency . Aim of this study was to test whether the gain in time-efficiency is at the loss of outcome . MATERIAL S AND METHODS We studied 13 patients having had a 2 weeks ADL based rehabilitation ( ABR ) and compared their clinical outcome parameters ( surface topograhy & Scoliometer angle ) to a group of 13 diagnosis- , age- , sex- , Cobb-angle and curve pattern-matched controls having a 4 weeks programme of exercise based rehabilitation ( EBR ) only . Average age in the study group was 15 years and average Cobb-angle 39 degrees . RESULTS Lateral deviation in the study group already after 2 weeks of ABR decreased 2 mm ( Formetric ) . Lateral deviation in the control group ( EBR ) decreased 1,9 mm . The changes were not significant . Thoracic as well as lumbar Scoliometer angle decreased highly significantly in both groups ( ABR : 1,8 degrees thoracic , 2,3 degrees lumbar ; EBR : 2,1 degrees thoracic , 2,6 degrees lumbar ) . The differences of outcome between the two groups were not significant . CONCLUSIONS ABR ( 2-week programme ) seems to provide similar results as EBR ( 4-week programme ) . ABR seems to provide a better time efficiency , however a prospect i ve controlled study with a larger sample of patients is desirable before final conclusions can be drawn Current work presents the results of spirometric examinations in 124 children aged 5 to 16 years ( mean age 12.1 years ) suffering from idiopathic scoliosis . Children were treated according to asymmetric respiratory exercises method applied in period of 24 days . Healthy children living in Upper Silesia industrial region were the control group . Examined scoliotic group was characterized by generally mild lung function impairment , although the values of spirometric indexes tended to deplete with time of duration and severity of the scoliosis . Especially the tendency of the forced expiratory volume in first second ( FEV1 ) decrease was apparent , as well as maximal expiratory flows MEF50 and MEF25 , in conjunction with Cobb angle increase . Slight but evident increase of forced vital capacity ( FVC ) and FEV1 was observed as a result of rehabilitation utilizing asymmetric respiratory exercises method |
1,670 | 24,143,945 | Among the clinical ly relevant molecules , those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery , as well as for directing towards an etiological diagnosis .
In conclusion , pulmonary biomarkers have the potential to provide information on the mechanisms underlying E COPD , and several correlate with clinical variables and outcomes . | Exacerbations of COPD ( E COPD ) represent a major burden for patients and health care systems .
Innovative sampling techniques have led to the identification of several pulmonary biomarkers .
Although some molecules are promising , their usefulness in clinical practice is not yet established .
According to published data several pulmonary biomarkers assessed in E COPD have the potential to illustrate the natural history of disease through the modification of their levels . | Introduction : Induced sputum is a non‐invasive method , and a useful tool to evaluate inflammatory cells and mediators in the airway lumen in the setting of acute exacerbation of chronic obstructive pulmonary disease ( AE COPD ) . However , the inhalation of hypertonic saline solution to induce sputum may cause a bronchoconstrictive response , so it is important to evaluate the success and safety of sputum induction ( SI ) BACKGROUND Endothelin (ET)-l is a bronchoconstrictor peptide produced in the airways . It has been implicated in the pathogenesis of asthma and virally mediated airway inflammation and may play a role in exacerbations of chronic obstructive pulmonary disease ( COPD ) . METHODS Seventy one patients with COPD were followed prospect ively and sample d for plasma and sputum ET-1 levels when stable and during an exacerbation . Sputum was also examined for cytokines , human rhinovirus , and Chlamydia pneumoniae . RESULTS Plasma ET-1 levels were available for 67 patients with stable COPD ( mean ( SD ) 0.58 ( 0.31 ) pg/ml ) ; 28 pairs of stable-exacerbation plasma sample s had a mean stable ET-1 level of 0.54 ( 0.30 ) pg/ml rising to 0.67 ( 0.35 ) pg/ml at exacerbation ( mean difference 0.13 , 95 % confidence interval ( CI ) 0.04 to 0.21 , p = 0.004 ) . Plasma ET-1 levels in the 67 patients with stable COPD were inversely correlated with baseline forced expiratory volume in one second ( FEV1;r = –0.29 , p = 0.022 ) and forced vital capacity ( FVC ; r = –0.38 , p = 0.002 ) . The change in plasma ET-1 levels during an exacerbation correlated with the change in oxygen saturation ( Sao 2;r = –0.41 , p = 0.036 ) . In 14 stable-exacerbation pairs of sputum sample s median stable ET-1 levels were 5.37 ( 0.97–21.95 ) pg/ml rising to 34.68 ( 13.77–51.95 ) pg/ml during an exacerbation ( mean difference 25.14 , 95 % CI 3.77 to 46.51 , p = 0.028 ) . This increase in sputum ET-1 levels correlated with the increase in plasma ET-1 levels ( r = 0.917 , p = 0.001 ) and sputum interleukin (IL)-6 levels ( r = 0.718 , p = 0.013 ) . CONCLUSIONS Sputum levels of ET-1 rise in COPD patients during an exacerbation and this is reflected by a smaller rise in plasma ET-1 levels . ET-1 may have a role in mediating airway inflammatory changes during exacerbations of COPD STUDY OBJECTIVES The etiologic role of bacterial pathogens isolated from sputum culture in 40 to 50 % of acute exacerbations of chronic bronchitis ( AECB ) is controversial . If bacterial pathogens cause these AECB , they should be associated with greater neutrophilic airway inflammation than pathogen-negative exacerbations . DESIGN This hypothesis was tested by comparing levels of interleukin (IL)-8 , tumor necrosis factor (TNF)-alpha , and neutrophil elastase ( NE ) in 81 sputum sample s obtained from 45 patients with AECB . Four groups were compared . In the first three groups , nontypable Haemophilus influenzae ( n = 20 ) , Haemophilus parainfluenzae ( n = 27 ) , and Moraxella catarrhalis ( n = 14 ) were isolated as sole pathogens , respectively . In the fourth group , only normal flora was isolated ( n = 20 ) . Paired sample s , obtained from individual patients at different times , that differed in their culture results were also compared . SETTING An outpatient research clinic at a Veterans Affairs Medical Center . PATIENTS These patients were participating in a prospect i ve , longitudinal study of the dynamics of bacterial infection in chronic bronchitis , for which they were seen in the study clinic on a monthly basis as well as when they were experiencing symptoms suggestive of AECB . INTERVENTIONS None . MEASUREMENTS AND RESULTS H influenzae exacerbations were associated with significantly higher sputum IL-8 , TNF-alpha , and NE . M catarrhalis exacerbations demonstrated significantly higher sputum TNF-alpha and NE when compared to pathogen-negative exacerbations . H parainfluenzae-associated exacerbations had an inflammatory profile similar to pathogen-negative exacerbations . Sputum elastase level distinguished bacterial from nonbacterial AECB and correlated with clinical severity of the AECB . CONCLUSIONS Increased airway inflammation associated with isolation of H influenzae and M catarrhalis supports an etiologic role of these pathogens in AECB Background Non-invasive phenotyping of chronic respiratory diseases would be highly beneficial in the personalised medicine of the future . Volatile organic compounds can be measured in the exhaled breath and may be produced or altered by disease processes . We investigated whether distinct patterns of these compounds were present in chronic obstructive pulmonary disease ( COPD ) and clinical ly relevant disease phenotypes . Methods Breath sample s from 39 COPD subjects and 32 healthy controls were collected and analysed using gas chromatography time-of-flight mass spectrometry . Subjects with COPD also underwent sputum induction . Discriminatory compounds were identified by univariate logistic regression followed by multivariate analysis : 1 . principal component analysis ; 2 . multivariate logistic regression ; 3 . receiver operating characteristic ( ROC ) analysis . Results Comparing COPD versus healthy controls , principal component analysis clustered the 20 best-discriminating compounds into four components explaining 71 % of the variance . Multivariate logistic regression constructed an optimised model using two components with an accuracy of 69 % . The model had 85 % sensitivity , 50 % specificity and ROC area under the curve of 0.74 . Analysis of COPD subgroups showed the method could classify COPD subjects with far greater accuracy . Models were constructed which classified subjects with ≥2 % sputum eosinophilia with ROC area under the curve of 0.94 and those having frequent exacerbations 0.95 . Potential biomarkers correlated to clinical variables were identified in each subgroup . Conclusion The exhaled breath volatile organic compound profile discriminated between COPD and healthy controls and identified clinical ly relevant COPD subgroups . If these findings are vali date d in prospect i ve cohorts , they may have diagnostic and management value in this disease Background : Chronic obstructive pulmonary disease ( COPD ) is characterised by an abnormal inflammatory response mainly to cigarette smoke that flares up during exacerbations of the disease ( E COPD ) . Reduced activity of histone deacetylases ( HDAC ) contributes to enhanced inflammation in stable COPD . It was hypothesised that HDAC activity is further reduced during E COPD and that theophylline , an HDAC activator , potentiates the anti-inflammatory effect of steroids in these patients . A study was performed to investigate HDAC activity during E COPD and the effects of theophylline on the anti-inflammatory effects of steroids in a r and omised single-blind controlled study . Methods : 35 patients hospitalised with E COPD and treated according to international guidelines ( including systemic steroids ) were r and omised to receive or not to receive low-dose oral theophylline ( 100 mg twice daily ) . Before treatment and 3 months after discharge , HDAC and nuclear factor-κB ( NF-κB ) activity in sputum macrophages , the concentration of nitric oxide in exhaled air ( eNO ) and total antioxidant status ( TAS ) , tumour necrosis factor α ( TNFα ) , interleukin (IL)-6 and IL8 levels in sputum supernatants were measured . Results : Patients receiving st and ard therapy showed decreased NF-κB activity , eNO concentration and sputum levels of TNFα , IL6 and IL8 , as well as increased TAS during recovery of E COPD , but HDAC activity did not change . The addition of low-dose theophylline increased HDAC activity and further reduced IL8 and TNFα concentrations . Conclusions : During E COPD , low-dose theophylline increases HDAC activity and improves the anti-inflammatory effects of steroids . Trial registration number : Although inflammatory changes are found throughout the airways of patients with chronic bronchitis , the mechanisms of the pathogenesis of chronic bronchitis are still unclear . The aim of this study was to investigate airways inflammation in patients with and without an exacerbation of bronchitis . Thirteen chronic bronchitic patients and nine normal subjects were studied . Eight of the patients were studied under baseline conditions ( B ) , and five during an exacerbation of bronchitis ( E ) . Bronchoscopy and bronchoalveolar lavage ( BAL ) with cytological analysis were performed , and the levels of granulocyte/macrophage colony-stimulating factor ( GM-CSF ) were determined in sera and in BAL supernatants by a solid phase enzyme immunoassay . Compared with patients under baseline conditions , chronic bronchitic patients with an exacerbation had increased numbers of BAL neutrophils ( 10+/-3 and 83+/-18x10(3 ) cells x mL(-1 ) , respectively ; p<0.0001 ) and of BAL eosinophils ( 1.9+/-0.5 and 6.7/-1.9x10(3 ) cells x mL(-1 ) , respectively ; p=0.014 ) . Patients with chronic bronchitis , as a whole , had significantly increased levels of BAL GM-CSF compared to control subjects ( 36+/-5 and 19+/-4 pg x mL(-1 ) , respectively ; p=0.035 ) , and similar levels of serum GM-CSF . Serum levels of GM-CSF were markedly increased in chronic bronchitic patients with an exacerbation , as compared with patients under baseline conditions ( 1.4+/-0.4 and 13+/-1 pg x mL(-1 ) , respectively ; p < 0.0001 ) . BAL levels of GM-CSF were also increased in chronic bronchitic patients with an exacerbation ( 25+/-5 and 54+/-8 pg x mL(-1 ) , respectively ; p=0.009 ) . During exacerbations of chronic bronchitis there are changes in the cell population s in bronchoalveolar lavage of patients consistent with a recruitment of polymorphonuclear leucocytes in the airway lumen . The increased levels of granulocyte/macrophage colony-stimulating factor might suggest a role for this cytokine in the inflammatory processes of chronic bronchitis The effects of broad-spectrum antibiotic and placebo therapy in patients with chronic obstructive pulmonary disease in exacerbation were compared in a r and omized , double-blinded , crossover trial . Exacerbations were defined in terms of increased dyspnea , sputum production , and sputum purulence . Exacerbations were followed at 3-day intervals by home visits , and those that resolved in 21 days were design ated treatment successes . Treatment failures included exacerbations in which symptoms did not resolve but no intervention was necessary , and those in which the patient 's condition deteriorated so that intervention was necessary . Over 3.5 years in 173 patients , 362 exacerbations were treated , 180 with placebo and 182 with antibiotic . The success rate with placebo was 55 % and with antibiotic 68 % . The rate of failure with deterioration was 19 % with placebo and 10 % with antibiotic . There was a significant benefit associated with antibiotic . Peak flow recovered more rapidly with antibiotic treatment than with placebo . Side effects were uncommon and did not differ between antibiotic and placebo Background : Chronic obstructive pulmonary disease ( COPD ) is characterized by airway inflammation and is associated with acute exacerbations . Macrolide antibiotics have been shown to exhibit anti-inflammatory effects in some chronic airway inflammatory diseases . Objective : The aim of this study was to assess the effect of treatment with erythromycin on airway inflammation and health outcome in COPD patients . Methods : We conducted a r and omized , placebo-controlled , double-blind trial of erythromycin for a period of 6 months . Thirty-six COPD patients were r and omized to treatment with oral erythromycin ( 125 mg , three times/day ) or placebo . The primary outcomes were neutrophil number in sputum and exacerbations . Results : Thirty-one patients completed the study . At the end of treatment , neutrophil counts in the sputum were significantly decreased in the group treated with erythromycin compared with placebo-treated patients ( p = 0.005 ) . Total cells in the sputum and neutrophil elastase in sputum supernatant were also significantly decreased in those treated with erythromycin compared with the placebo group ( p = 0.021 and p = 0.024 , respectively ) . The mean exacerbation rate was lower in the erythromycin group than in the placebo group ( relative risk = 0.554 , p = 0.042 ) . Kaplan-Meier survival analysis showed that erythromycin significantly delayed the time to the first COPD exacerbation compared with placebo ( p = 0.032 ) . Conclusions : Erythromycin treatment in COPD patients can reduce airway inflammation and decrease exacerbations and may therefore be useful in the management of COPD Background : The association between gastro-oesophageal reflux disease ( GORD ) and chronic obstructive pulmonary disease ( COPD ) exacerbation has so far remained unclear . Objective : To prospect ively establish the clinical significance of GORD symptoms on exacerbation . Methods : 82 patients with COPD and 40 age matched controls were enrolled in this study . Symptoms were evaluated by a question naire using the Frequency Scale for the Symptoms of GORD ( FSSG ) . Patients with COPD were prospect ively surveyed for 6 months , and episodes of exacerbation were identified using a diary based on modified Anthonisen ’s criteria . Exhaled breath condensate ( EBC ) pH was measured in both groups , and induced sputum was evaluated in patients with COPD . Results : Positive GORD symptoms were reported in 22 ( 26.8 % ) patients with COPD and in five ( 12.5 % ) controls ( p = 0.10 ) . The frequency of exacerbations was significantly associated with the FSSG score ( p = 0.03 , r = 0.24 , 95 % CI 0.02 to 0.43 ) . Multiple regression analysis revealed that GORD symptoms were significantly associated with the occurrence of exacerbations ( p<0.01 ; relative risk 6.55 , 95 % CI 1.86 to 23.11 ) . EBC pH was inversely correlated with FSSG score in both groups ( p = 0.01 , r = –0.37 , 95 % CI –0.55 to −0.14 in patients with COPD , and p<0.01 , r = –0.45 , 95 % CI –0.67 to −0.16 in control subjects ) . Conclusions : GORD symptoms were identified as an important factor associated with COPD exacerbation Chronic obstructive pulmonary disease ( COPD ) is characterized by an airways inflammation and by an enhanced generation of reactive oxygen species . The aim of our study was to assess the inflammation and the oxidative stress in airways of COPD patients with acute exacerbation of disease and in stability . Furthermore , we investigated the anti-inflammatory and antioxidant effects of 6 months treatment with carbocysteine lysine salt monohydrate ( SCMC-Lys ) in COPD . We studied 30 mild acute COPD , 10 mild stable COPD and 15 healthy subjects . 8-isoprostane and Interleukine-6 were measured in their breath condensate through immunoassay . Significantly higher concentrations of exhaled 8-isoprostane and Interleukine-6 were found in acute COPD patients compared to stable COPD and healthy controls ( 21.8+/-5.1 vs. 13.2+/-2.0 vs. 4.7+/-1.8 pg/ml and 7.4+/-0.9 vs. 5.8+/-0.2 vs. 2.7+/-0.6 pg/ml , p<0.0001 ) . COPD patients treated with SCMC-Lys showed a marked reduction of exhaled 8-isoprostane and Interleukine-6 ( 8.9+/-1.5 and 4.6+/-0.8 pg/ml , p<0.0001 ) . These findings suggest that there is an increase of 8-isoprostane and Interleukine-6 concentrations in the breath condensate of COPD patients compared to healthy controls especially during acute exacerbations of the disease . Moreover , we showed an anti-inflammatory and antioxidant effect of short-term administration of SCMC-Lys in COPD , suggesting the importance of a further placebo-controlled study that should evaluate the effects of this drug BACKGROUND The exhaled nitric oxide ( FeNO ) is a non-invasive marker of airway inflammation in asthma . A very recent statement has suggested FeNO as potential outcome in chronic obstructive pulmonary disease ( COPD ) . Recently , a new h and -held FeNO analyzer ( NIOX MINO ) has been developed . PATIENTS AND METHODS We have evaluated the NIOX MINO in COPD patients and monitored FeNO levels during 1-year assessment in the outpatient setting . Short-term variability in FeNO was compared using a NIOX MINO and a stationary chemiluminescence analyzer ( NOA , Sensormedics ) in healthy volunteers and COPD patients on two consecutive months . Long-term FeNO variability was assessed on a cohort of 70 COPD out patients measuring FeNO for 1 year . The intra-individual FeNO coefficient of variation ( eNOCoV ) was taken as index FeNO long-term variability . RESULTS In COPD there were no significant differences between NIOX MINO and NOA FeNO values recorded at baseline and 1 month later . Ninety five percent limits of agreement between NIOX MINO and NOA were-2.7 and 1.9ppb with significant reliability ( r=0.96 , p<0.0001 ) . Mean FeNO at baseline was 15.0+/-9.5ppb . Over the 1-year period the overall mean FeNO was 15.5+/-10.1ppb . The long-term eNOCoV was 33.9+/-16.4 % ( range 8.1 - 83.1 % ) , and it was significantly associated with exacerbation rate ( r=0.57 , p<0.0001 ) . CONCLUSION FeNO electrochemical h and -held analyzer is feasible in COPD showing good agreement with stationary chemiluminescence analyzer . COPD patients exhibit a wide range of FeNO levels and a high variability of FeNO over time , which was positively associated with the number of exacerbations Evidence suggests that eosinophilic airway inflammation is important in the pathogenesis of severe chronic obstructive pulmonary disease ( COPD ) exacerbations . The present authors tested the hypothesis that a management strategy that aims to reduce sputum eosinophil counts is associated with a reduction in exacerbations of COPD . A total of 82 patients with COPD were r and omised into two groups . One group was treated according to traditional guidelines ( British Thoracic Society ( BTS ) group ) and the other ( sputum group ) was treated with the additional aim of minimising eosinophilic airway inflammation , assessed using the induced sputum eosinophil count . The primary outcome was exacerbations , which were categorised as mild , moderate or severe . The frequency of severe exacerbations per patient per year was 0.5 and 0.2 in the BTS and sputum groups , respectively ( mean reduction 62 % ) . The majority of this benefit was confined to patients with eosinophilic airway inflammation . There was no difference in the frequency of mild and moderate exacerbations . The average daily dose of inhaled or oral corticosteroids during the trial did not differ between the groups . Out of 42 patients in the sputum group , 17 required regular oral corticosteroids to minimise eosinophilic airway inflammation . A management strategy that aims to minimise eosinophilic airway inflammation , as well as symptoms , is associated with a reduction in severe exacerbations of chronic obstructive pulmonary disease RATIONALE Whether the airway and systemic inflammatory profile in bacterial exacerbations of chronic obstructive pulmonary disease ( COPD ) is distinct from nonbacterial exacerbations is unclear . Previous studies have not used molecular typing of bacterial pathogens , which is required to accurately define bacterial infection in COPD . The relationship between clinical severity and course of exacerbation and inflammation is also not fully understood . OBJECTIVES To determine if ( 1 ) systemic and airway inflammation is distinct in new bacterial strain exacerbations and ( 2 ) clinical severity and resolution of exacerbations is related to airway and systemic inflammation . METHODS In a prospect i ve longitudinal cohort study in COPD , sputum and serum sample s obtained before , at , and following exacerbations during a 2-year period were studied . MEASUREMENTS AND MAIN RESULTS Clinical information , molecular typing of bacterial pathogens , sputum IL-8 , tumor necrosis factor (TNF)-alpha and neutrophil elastase , and serum C-reactive protein . From 46 patients , 177 exacerbations were grouped as new strain , preexisting strain , other pathogen , and pathogen negative . New strain exacerbations were associated with significantly greater increases from baseline in sputum TNF-alpha and neutrophil elastase , and in serum C-reactive protein compared with the other three groups . Increases in inflammatory markers were similar among the other three groups . Clinical resolution was accompanied by resolution of inflammation to preexacerbation levels , whereas persistent symptoms were paralleled by persistently elevated inflammation . Clinical exacerbation severity was significantly correlated with levels of all four markers . CONCLUSIONS Neutrophilic airway inflammation and systemic inflammation are more intense with well-defined bacterial exacerbations than with nonbacterial exacerbations . Clinical course of exacerbation and inflammation are closely linked Sputum induction ( SI ) is considered to be a safe tool for assessing airway inflammation in stable patients with COPD , but little is known about its safety during exacerbations . We therefore assessed the safety of SI during COPD exacerbations . SI data from 44 COPD patients were assessed both in the stable phase and during exacerbation . The median FEV1 for the stable phase and exacerbation were 61 % predicted ( interquartile range [ IQR ] , 49 to 74 % predicted ) and 51 % predicted ( IQR , 45 to 60 % predicted ) , respectively . The median decrease in FEV(1 ) with SI during an exacerbation was 0.27 L ( IQR , 0.17 to 0.40 L ) vs 0.28 L ( IQR , 0.22 to 0.44 L ) during the stable phase ( p = 0.03 ) . The patients experienced the associated dyspnea well ; no other adverse events occurred . All FEV1 values returned to within 90 % of their initial value within 30 min . A larger decrease in FEV1 due to SI during an exacerbation was associated with the following parameters in the stable phase of disease : lower total sputum cell count ( r = -0.37 ; p = 0.01 ) ; higher percentage of eosinophils ( r = 0.33 ; p = 0.04 ) ; and a larger decrease in FEV1 after SI ( r = 0.39 ; p = 0.03 ) . In a multivariate analysis , the only independent association was with the larger decrease in FEV1 in the stable phase . We concluded that SI can be safely carried out in patients with mild-to-moderate COPD who experience an exacerbation , and this occurs with no greater risk than in stable patients with COPD BACKGROUND Pathogenic bacteria colonize the airways of 30 % to 40 % of patients with COPD and cause approximately 50 % of exacerbations . New strains of nontypeable Haemophilus influenzae ( NTHI ) and Moraxella catarrhalis are associated with exacerbations . Antimicrobial protein/peptides ( AMPs ) play important roles in innate lung defense against pathogens . To our knowledge , the changes in AMP baseline levels in respiratory secretions during bacterial colonization and exacerbation have not been described . The objective of this study was to eluci date the effects of the acquisition of a new strain of pathogenic bacteria on the airway levels of AMPs in patients with COPD . METHODS One hundred fifty-three sample s from 11 patients were selected from COPD sputum sample s collected prospect ively over 6 years . Sample s were grouped as culture-negative ( no pathogenic bacteria ) , colonization , and exacerbation due to new strains of NTHI and M catarrhalis . Levels of lysozyme , lactoferrin , LL-37 , and secretory leukocyte protease inhibitor ( SLPI ) were measured by enzyme-linked immunosorbent assay and compared among groups by paired analysis . RESULTS Compared with baseline , sputum lysozyme levels were significantly lower during colonization and exacerbation by NTHI ( P = .001 and P = .013 , respectively ) and M catarrhalis ( P = .007 and P = .018 , respectively ) ; SLPI levels were lower with exacerbation due to NTHI and M catarrhalis ( P = .002 and P = .004 , respectively ) , and during colonization by M catarrhalis ( P = 032 ) . Lactoferrin levels did not change significantly ; LL-37 levels were higher during exacerbation by NTHI and M catarrhalis ( P = .001 and P = .018 , respectively ) . CONCLUSIONS Acquisition of NTHI and M catarrhalis is associated with significant changes in airway levels of AMPs , with larger changes in exacerbation . Airway AMP levels are likely to be important in pathogen clearance and clinical outcomes of infection in COPD BACKGROUND AND OBJECTIVE Although sputum culture in patients with an acute exacerbation of COPD is of uncertain value , it is routinely done . The ability to clinical ly identify patients likely or unlikely to yield bacterial sputum isolates would potentially reduce unnecessary tests . The objective of this study was to identify the clinical predictors of positive sputum cultures in this patient population . METHODS Consecutive patients with a COPD exacerbation requiring an emergency visit were prospect ively enrolled . Quantitative sputum culture was performed on-site . Data on current smoking , sputum purulence , FEV(1 ) , Medical Research Council chronic dyspnoea scale , BMI , severe exacerbations in the preceding year requiring hospitalization , PaO(2 ) , PaCO(2 ) , Acute Physiology and Chronic Health Evaluation ( APACHE ) II score , and oral and inhaled steroid use were recorded . RESULTS Of the 94 patients enrolled , sputum from 36 yielded bacterial pathogens . These patients were characterized by a higher frequency of purulent sputum , lower FEV(1 ) , BMI and PaO(2 , ) higher APACHE II score and more frequent use of inhaled steroids ( P < 0.05 ) . On multivariate regression , purulent sputum , FEV(1 ) and BMI were independent determinants of a positive sputum culture . Using receiver-operator-optimized thresholds for these variables ( purulent sputum , FEV(1 ) < 35 % predicted and BMI < or = 22 kg/m(2 ) ) , we proposed a regression coefficient-weighted prediction model that accurately determined the likelihood of sputum bacterial isolation . CONCLUSIONS A prediction model based on the variables of purulent sputum , FEV(1 ) and BMI predicted sputum culture result with about 90 % accuracy . Pending further validation , this model may save valuable healthcare re sources Study objectives The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable , and the determinants of these factors are poorly understood . We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD . Design Prospect i ve cohort study . Setting Outpatient Department , London Chest Hospital , London , UK . Patients Thirty-nine patients with COPD . Measurements We prospect ively studied 56 COPD exacerbations , obtaining clinical data and paired sputum and serum sample s at baseline and exacerbation . Qualitative and quantitative microbiology , polymerase chain reaction detection for rhinovirus , and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed . Results A total of 69.6 % of exacerbations were associated with a bacterial pathogen , most commonly Haemophilus influenzae . Rhinovirus was identified in 19.6 % of exacerbations . The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 ( r = 0.37 , p = 0.022 ) and fall in FEV1 ( r = 0.35 , p = 0.048 ) . Exacerbations with both rhinovirus and H influenzae had higher bacterial loads ( 108.56 cfu/mL vs 108.05cfu/mL , p = 0.018 ) and serum IL-6 ( 13.75 pg/mL vs 6.29 pg/mL , p = 0.028 ) than exacerbations without both pathogens . In exacerbations with both cold symptoms ( a marker of putative viral infection ) and a bacterial pathogen , the FEV1 fall was greater ( 20.3 % vs 3.6 % , p = 0.026 ) and symptom count was higher ( p = 0.019 ) than those with a bacterial pathogen alone . Conclusions The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism : bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity |
1,671 | 23,269,623 | Our meta- analysis provides comprehensive support for a role of circulation IGF-I and IGF-II in the etiology of CRC | Insulin-like growth factor peptides , play an important role in regulating cell growth , differentiation , and apoptosis , which has been demonstrated to promote the development of cancer .
The purpose of our study is to assess the association between circulation insulin-like growth factor peptides and colorectal cancer ( CRC ) risk . | This is the first study to investigate the associations of IGF-1 , IGF-2 and IGFBP-3 concentrations with the risk of colorectal cancer in prospect ively collected blood sample s from an Oriental population . Between 1986 and 1989 serum sample s were collected at baseline from 18 244 men , aged 45–65 years , without a history of cancer and living in Shanghai , China . IGF-1 , IGF-2 and IGFBP-3 were measured in the serum of 135 men who developed colorectal cancer over 12 years of follow-up and 661 control subjects drawn from the cohort , who were matched to the index cases by neighbourhood of residence , age , and year and month of sample collection . Serum IGF-1 was not associated with risk of colorectal cancer . IGF-2 and IGFBP-3 , on the other h and , exhibited statistically significant , positive associations with colorectal cancer risk when cases were confined to those diagnosed within a relatively short time period after enrolment ( within 8 years ) . After adjustment for body mass index , cigarette smoking and alcohol intake , men in the highest versus the lowest quintile of IGF-2 and IGFBP-3 showed odds ratios of 2.74 ( 95 % Cl = 1.67–4.50 ; 2-sided P for trend = 0.0008 ) and 2.85 ( 95 % Cl = 1.69–4.81 ; 2-sided P for trend = 0.01 ) , respectively . Our data thus suggest that circulating IGF-2 and IGFBP-3 can serve as early indicators of impending colorectal cancer . © 2001 Cancer Research Campaign There is some evidence that glucose and other factors related to glucose metabolism , such as insulin and insulin-like growth-factors ( IGFs ) may contribute to breast cancer development . The present study analyzed the hypothesis that serum glucose , insulin levels , and IGF-I pattern are associated with breast cancer using a nested case-control study . Between 1987 and 1992 , 10,786 women ages 35 - 69 were recruited in a prospect i ve study in Italy . Women with history of cancer and on hormone therapy were excluded at baseline . At recruitment , blood sample s were collected after a 12-h fast between 7:30 and 9:00 a.m. from all of the study participants . After 5.5 years , 144 breast cancer cases were identified among the participants of the cohort . Four matched controls were chosen for each breast cancer case from members of the cohort who did not develop breast cancer during the follow-up period . In premenopausal women , glucose was associated with breast cancer risk : the age , body mass index , and reproductive variable adjusted relative risk ( RR ) for the highest quartile of serum glucose versus the lowest was 2.8 [ 95 % confidence interval ( CI ) , 1.2 - 6.5 ] , and P for trend was 0.02 . Insulin showed a weaker association with breast cancer , the adjusted RR of the highest quartile versus the lowest was 1.7 ( 95 % CI , 0.7 - 4.1 ) , and P for trend was 0.14 , whereas the adjusted RR of the highest quartile of IGF-I was 3.1 ( 95 % CI , 1.1 - 8.6 ) , and P for trend was 0.01 . Increased levels of insulin-like growth factor binding protein-3 (IGFBP)-3 were related to breast cancer risk : the adjusted RR for the highest quartile was 2.1 ( 95 % CI , 0.95 - 4.75 ) , and P for trend was 0.02 . In postmenopausal women , the associations of glucose , insulin , and IGF-1 pattern were associated with breast cancer risk in heavier subjects characterized by a body mass index higher than 26 . These results indicate that chronic alteration of glucose metabolism is related to breast cancer development Blood concentrations of insulin-like growth factor-I ( IGF-I ) and insulin-like growth factor binding protein-3 ( IGFBP-3 ) have recently been associated with breast cancer risk , notably in women who developed breast cancer at a young age . Prospect i ve studies published so far , however , were relatively small and odds ratio ( OR ) estimates imprecise . We present the results of a large prospect i ve case-control study nested within the European Prospect i ve Investigation into Cancer and Nutrition on total IGF-I , IGFBP-3 and breast cancer risk including 1081 incident cases of invasive breast cancer and 2098 matched control subjects . Increasing IGF-I and IGFBP-3 concentrations were associated with a significant increase in breast cancer risk in women who developed breast cancer after 50 years of age ( highest vs lowest quintile OR 1.38 ( 95 % confidence interval ( CI ) 1.02 - 1.86 ) , P = 0.01 , and 1.44 ( 95 % CI 1.04 - 1.98 ) , P = 0.01 , respectively ) , but no relationship was observed in younger women ( OR = 1.03 ( 95 % CI 0.60 - 1.77 ) , P = 0.81 for IGF-I , and OR = 0.92 ( 95 % CI 0.50 - 1.70 ) , P = 0.69 for IGFBP-3 ) . There was , however , significant heterogeneity in the relationship of breast cancer with serum IGF-I and IGFBP-3 levels depending on the time interval between blood donation and tumor diagnosis . A reduction in breast cancer risk with increasing IGF-I concentrations was observed in cases with a diagnosis of cancer less than 2 years after blood donation , ( OR = 0.76 ( 95 % CI 0.57 - 1.03 ) ) , while an increase in risk was observed for women with a later diagnosis ( above or equal to two years after blood collection , OR = 1.51 ( 95 % CI 1.19 - 1.91 ) ) . A similar pattern was observed for IGFBP-3 . This study confirms previous findings for an association of serum IGF-I and IGFBP-3 concentrations with breast cancer risk , particularly for women with a later diagnosis of cancer , but it does not support the hypothesis of an involvement of IGF-I in younger women BACKGROUND Insulin-like growth factor I ( IGF-I ) stimulates cell proliferation and inhibits apoptosis in the lung and other tissues by interacting with the IGF-I receptor . The major binding protein for IGF-I , insulin-like growth factor-binding protein 3 ( IGFBP-3 ) , modulates the effects of IGF-I but also inhibits cell growth and induces apoptosis independent of IGF-I and its receptor . In a prospect i ve study of men in Shanghai , China , we examined the association between serum levels of IGF-I and IGFBP-3 and the subsequent risk of lung cancer . METHODS From 1986 to 1989 , serum was collected from 18,244 men aged 45 - 64 years living in Shanghai without a history of cancer . We analyzed IGF-I and IGFBP-3 levels in serum from 230 case patients who developed incident lung cancer during follow-up and from 740 control subjects . RESULTS Among 230 case patients and 659 matched control subjects , increased IGF-I levels were not associated with increased risk of lung cancer . However , for subjects in the highest quartile relative to the lowest quartile of IGFBP-3 , the odds ratio ( OR ) for lung cancer , adjusted for smoking and IGF-I , was 0.50 ( 95 % confidence interval [ CI ] = 0.25 to 1.02 ) . When the analysis was restricted to ever smokers ( 184 case patients and 344 matched control subjects ) , the OR for lung cancer in men in the highest quartile of IGFBP-3 relative to those in the lowest quartile , adjusted for smoking and IGF-I , was 0.41 ( 95 % CI = 0.18 to 0.92 ) . CONCLUSIONS In this prospect i ve study of Chinese men , higher serum levels of IGF-I did not increase the risk of lung cancer . However , subjects with higher serum levels of IGFBP-3 were at reduced risk of lung cancer . This finding is consistent with experimental data that indicate that IGFBP-3 can inhibit cellular proliferation and induce apoptosis independent of IGF-I and the IGF-I receptor Insulin-like growth factor (IGF)-I induces growth in pancreatic cancer cells and blockade of the IGF-I receptor has antitumour activity . The association of plasma IGF-I and IGF binding protein-3 ( IGFBP-3 ) with pancreatic cancer risk has been investigated in two small studies , with conflicting results . We conducted a nested case – control study within four large , prospect i ve cohorts to investigate whether prediagnostic plasma levels of IGF-I , IGF-II , and IGFBP-3 were associated with pancreatic cancer risk . Plasma levels in 212 cases and 635 matched controls were compared by conditional logistic regression , with adjustment for other known pancreatic cancer risk factors . No association was observed between plasma levels of IGF-I , IGF-II , or IGFBP-3 and incident diagnosis of pancreatic cancer . Relative risks for the highest vs the lowest quartile of IGF-I , IGF-II , and IGFBP-3 were 0.94 ( 95 % confidence interval ( CI ) , 0.60–1.48 ) , 0.96 ( 95 % CI , 0.61–1.52 ) , and 1.21 ( 95 % CI , 0.75–1.92 ) , respectively . The relative risk for the molar ratio of IGF-I and IGFBP-3 , a surrogate measure for free IGF-I , was 0.84 ( 95 % CI , 0.54–1.31 ) . Additionally , no association was noted in stratified analyses or when requiring longer follow-up . In four prospect i ve cohorts , we found no association between the risk of pancreatic cancer and prediagnostic plasma levels of IGF-I , IGF-II , or IGFBP-3 BACKGROUND Insulin-like growth factor-I ( IGF-I ) is a potent mitogen for normal and neoplastic cells , whereas IGF-binding protein-3 ( IGFBP-3 ) inhibits cell growth in many experimental systems . Acromegalics , who have abnormally high levels of growth hormone and IGF-I , have higher rates of colorectal cancer . We therefore examined associations of plasma levels of IGF-I and IGFBP-3 with the risk of colorectal cancer in a prospect i ve case-control study nested in the Physicians ' Health Study . METHODS Plasma sample s were collected at baseline from 14916 men without diagnosed cancer . IGF-I , IGF-II , and IGFBP-3 were assayed among 193 men later diagnosed with colorectal cancer during 14 years of follow-up and among 318 age- and smoking-matched control subjects . All P values are two-sided . RESULTS IGFBP-3 levels correlated with IGF-I levels ( r=.64 ) and with IGF-II levels ( r=.90 ) . After controlling for IGFBP-3 , age , smoking , body mass index ( weight in kg/[height in m]2 ) , and alcohol intake , men in the highest quintile for IGF-I had an increased risk of colorectal cancer compared with men in the lowest quintile ( relative risk [RR]=2.51 ; 95 % confidence interval [CI]=1.15 - 5.46 ; P for trend = .02 ) . After controlling for IGF-I and other covariates , men with higher IGFBP-3 had a lower risk ( RR=0.28 ; 95 % CI=0.12 - 0.66 ; P for trend = .005 , comparing extreme quintiles ) . The associations were consistent during the first and the second 7-year follow-up intervals and among younger and older men . IGF-II was not associated with risk . CONCLUSIONS Our findings suggest that circulating IGF-I and IGFBP-3 are related to future risk of colorectal cancer Insulin-like growth factors ( IGFs ) may play a role in prostate growth , hyperplasia , and malignancy . High plasma IGF-I has been associated with increased prostate cancer risk . In a prospect i ve , cohort , case-control study in the Baltimore Longitudinal Study on Aging population , we examined prostate volume by magnetic resonance imaging , and prostate-specific antigen ( PSA ) , IGF-I , IGF-II , and IGF-binding protein-3 ( IGFBP-3 ) in sera obtained approximately 9 yr before diagnosis of prostate cancer in cases ( n = 72 ) or age-matched controls ( n = 127 ) and in 76 additional Baltimore Longitudinal Study on Aging men ( normal subjects ) with measured prostate volumes and no prostate cancer . We calculated adjusted odds ratios ( OR ) by logistic regression , relative risks for significant ORs , and receiver operator curves for prostate cancer , using serum measures alone and in combination . Adjusted ORs for the high vs. low tertile were : for IGF-I , 3.1 [ confidence interval ( CI ) , 1.1 - 8.7 ] ; for IGF-II , 0.2 ( CI , 0.07 - 0.6 ) ; for IGFBP-3 , 0.71 ( CI , 0.3 - 1.7 ) ; and for PSA , 12.5 ( CI , 3.8 - 40.9 ) . For significant ORs , relative risk estimates remained significant at 2.0 for IGF-I , 0.3 for IGF-II , and 5.5 for PSA . Receiver operator curves showed PSA to be the most powerful predictor of prostate cancer . Adding IGF-II to PSA improved prediction . IGF-II was significantly and inversely related ( r = -0.219 ; P < 0.01 ) and PSA was directly and significantly related ( r = 0.461 ; P < 0.0001 ) to prostate volume , whereas IGF-I and IBFBP-3 were not . High IGF-I and low IGF-II are independently associated with increased risk of prostate cancer , but PSA level is a much stronger predictor of prostate cancer in the ensuing 10 yr than either IGF-I or IGF-II . The absence of a relationship of IGF-I to prostate size is inconsistent with increased ascertainment in men with large prostates as the source of greater prostate cancer risk associated with IGF-I. Our data suggest that IGF-II may inhibit both prostate growth and development of prostate cancer Recently , a number of prospect i ve studies showed evidence that the growth hormone/insulin-like growth factor I ( IGF-I ) axis may be important in the development of colorectal cancer . However , only a few studies have reported on the possible relationship of colorectal cancer risk with circulating levels of IGF-II , which are not growth hormone dependent and which do not vary with alterations in energy balance . In a case-control study of 102 cases and 200 matched controls nested within a cohort of 14,275 women in New York , we examined the relationship between colorectal cancer risk and prediagnostic serum levels of IGF-II . Conditional logistic regression analysis showed an odds ratio ( OR ) for colorectal cancer of 2.02 ( 95 % confidence interval ( CI ) : 0.83 - 4.93 ) , comparing the upper to lower quintile of IGF-II . This association was slightly attenuated after excluding IGF-II measurements in serum sample s taken within 1 year before case diagnosis ( OR of 1.81 ; 95 % CI : 0.71 - 4.64 ) and moderately attenuated after excluding IGF-II measurements in serum sample s taken within 2 years before case diagnosis ( OR of 1.47 ; 95 % CI : 0.56 - 3.91 ) . Adjustment for IGF-1 , IGF binding protein (BP)-1 , IGFBP-3 , smoking , or body mass index did not substantially alter the association , whereas adjustment for IGFBP-2 moderately attenuated the relationship . Our results confirm those of three recent case-control studies , and collectively these results suggest a possible increase in colorectal cancer risk among subjects with comparatively elevated serum IGF-II . Mechanisms that might cause the increase in IGF-II levels are unknown but may include loss of parental imprinting of the IGF-II gene We set out to study the relationship between circulating levels of IGF-I and its major binding protein ( IGFBP-3 ) in relation to ovarian cancer risk . We conducted a case-control study nested within the European Prospect i ve Investigation into Cancer and Nutrition . Levels of IGF-I and IGFBP-3 were measured in prediagnostic serum sample s of 214 women who subsequently developed ovarian cancer , and 388 matched control subjects . Conditional logistic regression models were used to estimate relative risks of ovarian cancer by tertiles of IGF-I and IGFBP-3 levels . For all women , there was no association between the circulating IGF-I or IGFBP-3 levels and the risk of ovarian cancer . However , among women diagnosed with ovarian cancer aged 55 or younger , the relative risk was higher in the middle or top tertiles of serum IGF-I , when compared with women in the lowest tertile ( odds ratios ( OR ) = 1.8 ( 95%CI 0.7 - 4.3 ) and OR = 2.4 ( 95%CI 0.9 - 6.4 ) ; P(trend ) = 0.08 ) respectively . These results were adjusted for body mass index , previous hormone use , fertility problems , and parity . Restricting the analysis to women who were premenopausal at blood donation , relative risks for ovarian cancer diagnosed before age 55 were higher ( OR = 5.1 ( 95%CI 1.5 - 18.2 ) and OR = 5.6 ( 95%CI 1.5 - 20.8 ) respectively , for second and third tertiles ; P(trend ) = 0.02 ) . Adjustment for serum IGFBP-3 levels only slightly attenuated relative risk estimates . Relations between IGFBP-3 and ovarian cancer before age 55 were in the same direction as for IGF-I , but less strong and statistically not significant . In women aged over 55 , there was no association between serum IGF-I or IGFBP-3 and ovarian cancer risk . Our results suggest that the circulating levels of IGF-I may play a potentially important role in the development of ovarian cancer in women of a pre- or perimenopausal age Chronically elevated plasma insulin levels have been postulated to increase colon cancer risk , either directly through colonic insulin receptors or indirectly through downregulation of IGFBP-1 and /or IGFBP-2 , thus increasing IGF activity . Our aim was to examine the relationships of plasma insulin and IGFBPs-1 and -2 with risks of colon and rectal cancers . We conducted a case-control study nested within the prospect i ve Northern Sweden Health and Disease Cohort . Insulin and IGFBPs were measured in prediagnostic plasma sample s from 168 men and women who developed cancers of the colon ( n = 110 ) or rectum ( n = 58 ) and from 336 matched controls . Conditional logistic regression analyses showed no significant relationship of plasma insulin with risk of colon or rectal cancer . In subjects whose blood sample s had been collected after more than 4 hr of fasting , insulin showed a moderate but still nonsignificant association with colorectal cancer risk [ ORs over quartiles : 1.00 , 0.70 ( 95 % CI 0.35 - 1.39 ) , 1.06 ( 95 % CI 0.55 - 2.07 ) , 1.63 ( 95 % CI 0.82 - 3.24 ) ; p(trend ) = 0.10 ] . Plasma IGFBP-1 and IGFBP-2 showed no association with risk of colon and /or rectal cancer , either in the full study population or among the fasting subjects . Our results only moderately support a possible relationship of chronic hyperinsulinemia with colon cancer risk |
1,672 | 27,232,073 | Devices that reroute sounds from an ear with a severe to profound hearing loss to an ear with minimal hearing loss may improve speech perception in noise when signals of interest are located toward the impaired ear .
However , the same device may also de grade speech perception as all signals are rerouted indiscriminately , including noise .
For the same reason , it remains unclear whether cochlear implantation can improve the ability to localize sounds despite restoring bilateral input . | OBJECTIVES A systematic review of the literature and meta- analysis was conducted to assess the nature and quality of the evidence for the use of hearing instruments in adults with a unilateral severe to profound sensorineural hearing loss . | OBJECTIVE To evaluate the sound localization capabilities of patients with unilateral , profound sensorineural hearing loss who had been treated with either a bone-anchored hearing device ( Baha BP100 ) or a TransEar 380-HF bone-conduction hearing device . STUDY DESIGN Nonr and omized , prospect i ve study . SETTING Tertiary referral private practice . PATIENTS Patients with unilateral , profound sensorineural hearing loss treated with a BP100 ( n = 10 ) or a TransEar ( n = 10 ) device . Patients wore the hearing device for at least 1 month and had normal hearing in the contralateral ear . Ten patients with normal , bilateral hearing were used for control . INTERVENTIONS Sound localization of a 3-second recorded sound with and without a TransEar or Baha device was assessed using an array of 7 speakers at head level separated by approximately 45 degrees . The recorded sounds were that of a barking dog or a police siren . R and omized trials of 4 presentations per speaker were given for each hearing condition . MAIN OUTCOME MEASURES Sound localization was assessed by the accuracy in response and the generalized laterality of response . RESULTS The mean accuracy of speaker localization was 24 % and 26 % for the aided condition using the BP100 and TransEar devices , respectively . The mean accuracy of laterality judgment was 59 % and 69 % for the aided condition using the BP100 and TransEar devices , respectively . These results were only slightly better than chance . There was no statistical difference in localization accuracy or laterality judgment between the BP100 and TransEar groups . CONCLUSION Neither the BP100 nor the TransEar device improved sound localization accuracy or laterality judgment ability in patients with unilateral , profound sensorineural hearing loss compared with performance in the unaided condition Objective : To investigate the effect of low-frequency attenuation of Bone-Anchored Hearing Aids ( Bahas ) in users with single-sided sensorineural deafness ( SSD ) . The underlying notion is that low-frequency sounds up to approximately 1500 Hz reach the contralateral ear without significant attenuation and that Bahas tend to show more distortion at lower frequencies . Furthermore , to transmit low frequencies , higher moving masses are needed when compared with high frequencies . Design : A prospect i ve study with 10 adults , experienced Baha Divino users with SSD . Speech underst and ing in noise was measured without Baha and with Baha , with three different setting s of low-frequency attenuation , namely up to 270 , 630 , and 1500 Hz . Tests were performed in two different spatial arrangements . In one placement , speech was emitted from a loudspeaker on the side of the Baha ear and noise from a loudspeaker in front of the listener ( S90N0 ) . In the other placement , the sound sources were switched ( S0N90 ) . Participants rated the subjective sound quality of the two most extreme Baha setting s using analog visual scales after a short acclimatization time of 15 mins . Results : In setting S90N0 , the use of a Baha improved speech underst and ing in noise significantly ( average improvement 2.8 to 3.1 dB , p = 0.006 ) . These improvements did not vary significantly with the chosen low-frequency attenuation . In setting S0N90 , a smaller but detrimental effect of the Baha was found ( −0.9 to −1.7 dB , p = 0.006 to 0.03 ) . This detrimental effect was significantly smaller at the highest cutoff frequency of 1500 Hz than at 270 Hz ( p = 0.013 ) . At the cutoff frequency of 270 Hz , loudness and reverberation were judged higher than at 1500 Hz . There was no significant difference in brightness , softness , clarity , or fullness . Conclusion : High cutoff levels of up to 1500 Hz for low-frequency signals do not compromise the benefit of Baha in SSD for noise arriving from the front and speech presented on the side of the Baha . If noise is presented from the side of the Baha , the detrimental effect on speech underst and ing can be reduced by higher cutoff frequencies . If frequencies < 1500 Hz do not need to be transmitted , lower moving masses of the Baha are required and smaller devices for patients with SSD may be possible BACKGROUND Cochlear implantation ( CI ) has proven in long term prospect i ve trials to reduce significantly incapacitating tinnitus in single sided deafness ( SSD ) . Discussion arises whether electrical stimulation near the round window ( RW ) is also able to reduce tinnitus . AIM to assess whether electrical stimulation of the basal first 4 intracochlear electrodes of a CI could sufficiently reduce tinnitus and to compare these results with stimulation with all CI electrodes . MATERIAL AND METHODS 7 patients who met the criteria of severe tinnitus due to SSD were implanted with a Med-El Sonata Ti100 with a FlexSoftTM or Flex24TM electrode . After 4 weeks only the basal electrode pair ( E12 ) nearest to the RW was activated . Each week the following pair was activated until the 4th pair . Thereafter all electrodes were activated . Tinnitus was assessed before CI surgery and before each electrode pair was activated . When all electrodes were fitted , evaluation was done after 1 , 3 and 6 months . Tinnitus was assessed with Visual Analogue Scale ( VAS ) for loudness , psychoacoustic tinnitus loudness comparison at 1 kHz and Tinnitus Question naire ( TQ ) for the effect on quality of life . To evaluate the natural evolution , a tightly matched control group with severe tinnitus due to SSD was followed prospect ively . RESULTS All the tinnitus outcome measures remained unchanged with 1 , 2 , 3 or 4 activated electrode pairs . With complete CI activation , the tinnitus decreased significantly comparable with earlier reports . Pre-implantation the tinnitus loudness was 8.2/10 on the VAS and was reduced to 4.1/10 6 months postimplantation . Psychometrically the loudness level went from 21.7 dB SL ( SD : 16.02 ) to 7.5 dB SL ( SD : 5.24 ) and the TQ from 60/84 to 39/84 . The non-implanted group had no decrease of the tinnitus , the average VAS remained stable at 8.9/10 throughout the follow-up period of 6 months . CONCLUSION with the current stimulation parameters electrical stimulation in the first 8e10 mm of the basal part of the scala tympani is insufficient to reduce tinnitus . However , stimulation over the complete CI length yields immediate tinnitus reduction confirming earlier results Objective : To longitudinally evaluate short- and long-term subject satisfaction/benefit perception , device usage rates , complication rates , and external device repair rates of bone-anchored hearing aid ( BAHA ) implantation on a cohort of adult subjects with profound unilateral sensorineural hearing loss ( PUSHL ) . Study Design : Prospect i ve clinical trial . Setting : Tertiary referral center . Patients : Fifty-six adults with PUSHL , 21 of which underwent BAHA implantation ( followed for an average of 3.2 years after implantation ; range , 0.8 - 4.6 yr ) . Main Outcome Measures : Short- and long-term satisfaction/benefit perception outcomes consisting of the Glasgow Hearing Aid Benefit Profile , Abbreviated Profile of Hearing Aid Benefit , and Single-Sided Deafness Question naire , including a comparison of results between implanted and nonimplanted subjects . Short- and long-term device usage rates , complications , and device failure issues also were carefully documented . Results : There were statistically significant improvements in nearly all measures of benefit perception documented as well as a high rate of long-term device usage ( 81 % ) . Although satisfaction and benefit perception outcomes generally tended to regress over time when compared with initial short-term outcomes , long-term scores still tended to be significantly improved nevertheless as compared with preoperative levels . Approximately 38 % of implants experienced severe local skin reactions ( Grade 2 and above ) around the implant site at some point throughout the follow-up period , whereas only one ( 4.8 % ) required implant removal . 66.7 % of subjects required repair of their external sound processor . Conclusion : BAHA implantation seems to provide a high level of short- and long-term perceived benefit and satisfaction in subjects with PUSHL and high rate of long-term device usage . Implant site adverse local skin reactions and repairs of the external sound processor were quite common Objectives : One purpose of this investigation was to evaluate the effect of a unilateral bone-anchored hearing aid ( Baha ) on horizontal plane localization performance in single-sided deaf adults who had either a conductive or sensorineural hearing loss in their impaired ear . The use of a 33-loudspeaker array allowed for a finer response measure than has previously been used to investigate localization in this population . In addition , a detailed analysis of error patterns allowed an evaluation of the contribution of r and om error and bias error to the total rms error computed in the various conditions studied . A second purpose was to investigate the effect of stimulus duration and head-turning on localization performance . Design : Two groups of single-sided deaf adults were tested in a localization task in which they had to identify the direction of a spoken phrase on each trial . One group had a sensorineural hearing loss ( SNHL group ; N = 7 ) , and the other group had a conductive hearing loss ( CHL group ; N = 5 ) . In addition , a control group of four normal-hearing adults was tested . The spoken phrase was either 1250 msec in duration ( a male saying “ Where am I coming from now ? ” ) or 341 msec in duration ( the same male saying “ Where ? ” ) . For the longer- duration phrase , subjects were tested in conditions in which they either were or were not allowed to move their heads before the termination of the phrase . The source came from one of nine positions in the front horizontal plane ( from −79 ° to + 79 ° ) . The response range included 33 choices ( from −90 ° to + 90 ° , separated by 5.6 ° ) . Subjects were tested in all stimulus conditions , both with and without the Baha device . Overall rms error was computed for each condition . Contributions of r and om error and bias error to the overall error were also computed . Results : There was considerable intersubject variability in all conditions . However , for the CHL group , the average overall error was significantly smaller when the Baha was on than when it was off . Further analysis of error patterns indicated that this improvement was primarily based on reduced response bias when the device was on ; that is , the average response azimuth was nearer to the source azimuth when the device was on than when it was off . The SNHL group , on the other h and , had significantly greater overall error when the Baha was on than when it was off . Collapsed across listening conditions and groups , localization performance was significantly better with the 1250 msec stimulus than with the 341 msec stimulus . However , for the longer- duration stimulus , there was no significant beneficial effect of head-turning . Error scores in all conditions for both groups were considerably larger than those in the normal-hearing control group . Conclusions : On average , single-sided deaf adults with CHL showed improved localization ability when using the Baha , whereas single-sided deaf adults with SNHL showed a decrement in performance when using the device . These results may have implication s for clinical counseling for patients with unilateral hearing impairment Abstract Conclusion : The bone-anchored hearing aid ( BAHA ) system can offer significant benefits to patients with single-sided deafness ( SSD ) , primarily by lifting the head shadow effect . Objective : To evaluate the efficacy of BAHA for SSD by comparing pre- and postoperative speech , spatial and qualities of hearing scale ( SSQ ) scores . Methods : This was a prospect i ve study conducted within a tertiary auditory implant department . The inclusion criteria were unilateral profound hearing loss with normal or mild high frequency hearing loss in the hearing ear ( pure tone average better than or equal to 25 dBHL measured at 0.5 , 1 , 2 and 3 kHz ) and subjective benefits reported by patients following a home trial with a BAHA Softb and . Patients who met the above criteria and opted for surgery were asked to complete the SSQ question naire . The postoperative SSQ response was collected after at least 6 months of consistent BAHA usage . Results : This study included 25 adult patients ( mean age at implantation 57.5 years ) . There was a statistically significant improvement in the average SSQ score in all three sections of the question naire with the use of the BAHA . Our patients experienced most marked benefits in speech hearing in challenging listening situations . All patients remain consistent users and there has been no explantation to date To investigate the implication s of duration of deafness in the rehabilitation of unilateral deafness utilizing cochlear implantation . From the ongoing prospect i ve cochlear implantation in unilateral deafness study , we looked at five adults who received a cochlear implant for long-term unilateral deafness . Speech perception in noise and subjective evaluation of the benefits of cochlear implantation were measured at 3 , 6 , and 12 months after implantation . The results were analyzed and compared with published data from normal hearing individuals and adults using cochlear implants bilaterally . Analysis of speech perception in noise showed significant improvement for three spatial configurations : speech and noise from the front ( S0/N0 ; P=0.003 ) , speech from the front and noise from the normal hearing ear ( S0/NHE ; P=0.001 ) , speech from the implanted ear , and noise from the normal hearing ear ( SCI/NHE ; P<0.001 ) . The scores obtained at 12 months after surgery improved to values similar to those obtained by individuals with normal hearing . The results of subjective measures showed significant improvement in hearing over time to the scores obtained by individuals with a bilateral cochlear implants and those with normal hearing . In this study , older adults with more than 25 years of unilateral deafness obtained scores in speech perception testing and in subjective evaluation that are similar to those attained by individuals with normal hearing and /or those with bilateral cochlear implants . Therefore , patients with postlingual unilateral deafness should not be excluded as cochlear implant c and i date s on the basis of a long duration of deafness The objective of the present pilot study is to evaluate the effectiveness of three conventional contralateral routing of sound ( CROS ) hearing aids in adults with unilateral inner ear deafness . The study included tertiary referral center . Ten patients with unilateral inner ear deafness and normal hearing in the contralateral ear were selected to evaluate three different methods of amplification : the CROS hearing aid , the completely in the canal hearing aid and the bone-anchored hearing aid CROS ( BAHA ) . Each of the three hearing aids was tried in a r and om order for a period of 8 weeks . Audiometric performance , including speech-in-noise , directional hearing and subjective benefit were measured after each trial period , using the APHAB , SSQ and single-sided deafness question naire . Sound localization performance was essentially at chance level in all four conditions . Mixed results were seen on the other patient outcome measures that alternated in favor of one of the three CROS devices . After the trial , three patients chose to be fitted with the BAHA CROS and one with the conventional CROS . In conclusion , most of the patients experienced some degree of benefit with each of the three hearing aids . Preference for one of the three hearing aids was independent of the order in which they were tried . It would be worthwhile to formulate selection criteria ; still , we recommend that all patients with unilateral inner ear deafness should be offered a trial with at least the BAHA CROS Objective Monaural hearing imposes constraints under many listening conditions . The authors compared the effects of a semi-implantable bone conductor , the Entific bone anchored hearing aid , with conventional contralateral routing of offside signal amplification to assess rehabilitative benefit in adults with unilateral deafness . Design Prospect i ve trials of subjects with unilateral deafness using benefit surveys , source identification testing , and hearing in noise testing . Setting Tertiary referral center , outpatient surgical and audiologic services . Patients Adults with unilateral deafness ( pure tone average > 90 dB , SD < 20 % ) after acoustic neuroma excision ( n = 7 ) , meningitis ( n = 1 ) , sudden sensorineural hearing loss ( n = 1 ) , and sudden sensorineural hearing loss with chronic suppurative otitis media ( n = 1 ) . Entry criteria included normal hearing in the contralateral ear ( pure tone average < 25 dB , SD > 80 % ) . Intervention Subjects were fitted with contralateral routing of offside signal amplification devices for 1 month and tested with contralateral routing of offside signal before mastoid implantation of the deaf ear , fitting , and testing for bone anchored hearing aid . Outcome measures Subjects ' assessment of experience with their devices and patterns of use , 2 ) source azimuth identification in noise test , and 3 ) speech discrimination in quiet and in noise under conditions of noise-front , noise-to-normal-ear , and noise-to-deaf-ear . Results There was consistent satisfaction with bone anchored hearing aid implantation and amplification , and poor acceptance of contralateral routing of offside signal amplification . Sound localization was poor at baseline and with both bone anchored hearing aid and contralateral routing of offside signal . Relative to baseline , contralateral routing of offside signal and bone anchored hearing aid produced significantly better speech recognition in noise under most conditions . The bone anchored hearing aid enabled significantly better speech recognition than contralateral routing of offside signal in quiet and in a composite of noise conditions . The advantages may relate to averting the interference of speech signals delivered to the better ear , as occurs with conventional contralateral routing of offside signal amplification . Conclusions Preliminary data in subjects with normal monaural hearing indicate that vibromechanical stimulation with the bone anchored hearing aid overcomes some of the negative head shadow effects in unilateral deafness . The bone anchored hearing aid system , when placed on the side of a deaf ear , yields greater benefit in subjects with normal monaural hearing than does contralateral routing of offside signal amplification . It seems that this rehabilitative approach can exp and the sound field of monaural listeners in further enhancing speech underst and ing . Observations suggest that further underst and ing of bone conduction as implemented in transcranial stimulation will guide further options for patients with monaural hearing . Longer follow-up will help to determine whether communicative skill improvements with the bone anchored hearing aid outweigh the disadvantages of implantation surgery , costs , and device maintenance OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity UNLABELLED A unilateral hearing loss is characterized by reduced hearing in one ear . The problems caused by sensory deprivation can be minimized with the use of hearing aids ( HA ) . AIM To analyze the correlation between the prescribed grain and the insertion gain difference and with the results obtained regarding the benefit and satisfaction with the use of hearing aids in unilateral hearing impaired patients . MATERIAL S AND METHODS Prospect i ve study with 15 subjects , mean age of 41.6 years , of both genders , users of hearing aids effectively . We used the International Question naire Results for hearing aids ( International Outcome Inventory for Hearing Aids - IOI-HA ) , measured with a probe microphone . RESULTS The mean values in the analyses of the IOI-HA per item were positive and higher than four points . In relation to the objective measures , the frequencies in which we obtained the gain values which were closer to the target were : 1 K Hz , 2 K Hz and 500 Hz , respectively . CONCLUSION The satisfaction of individuals using hearing aid unilaterally is not completely correlated to the prescribed gain , because even if the target is not being reached in some frequencies , the individuals were pleased as to the use of their hearing aids Objective : Vibromechanical stimulation with a semi-implantable bone conductor ( Entific BAHA device ) overcomes some of the head-shadow effects in unilateral deafness . What specific rehabilitative benefits are observed when the functional ear exhibits normal hearing versus moderate sensorineural hearing loss ( SNHL ) ? Design : The authors conducted a prospect i ve trial of subjects with unilateral deafness in a tertiary care center . Patients : This study comprised adults with unilateral deafness ( pure-tone average [ PTA ] > 90 dB ; Sp . D. < 20 % ) and either normal monaural hearing ( n = 18 ) or moderate SNHL ( PTA = 25 - 50 dB : Sp . D. > 75 % ) in the contralateral functional ear ( n = 5 ) . Interventions : Subjects were fit with contralateral routing of signal ( CROS ) devices for 1 month and tested before ( mastoid ) implantation , fitting , and testing with a bone-anchored hearing aid ( BAHA ) . Outcome Measures : Outcome measures were : 1 ) subjective benefit ; 2 ) source localization tests ( Source Azimuth Identification in Noise Test [ SAINT ] ) ; 3 ) speech discrimination in quiet and in noise assessed with Hearing In Noise Test ( HINT ) protocol s. Results : There was consistent satisfaction with BAHA amplification and poor acceptance of CROS amplification . General directional hearing decreased with CROS use and was unchanged by BAHA and directional microphone aids . Relative to baseline and CROS , BAHA produced significantly better speech recognition in noise . Twenty-two of 23 subjects followed up in this study continue to use their BAHA device over an average follow-up period of 30.24 months ( range , 51 - 12 months ) . Conclusion : BAHA amplification on the side of a deaf ear yields greater benefit in subjects with monaural hearing than does CROS amplification . Advantages likely related to averting the interference of speech signals delivered to the better ear , as occurs with conventional CROS amplification , while alleviating the negative head-shadow effects of unilateral deafness . The advantages of head-shadow reduction in enhancing speech recognition with noise in the hearing ear outweigh disadvantages inherent in head-shadow reduction that can occur by introducing noise from the deaf side . The level of hearing impairment correlates with incremental benefit provided by the BAHA . Patients with a moderate SNHL in the functioning ear perceived greater increments in benefit , especially in background noise , and demonstrated greater improvements in speech underst and ing with BAHA amplification Objective Compare preoperative and postoperative performance in patients undergoing cochlear implantation ( CI ) for unilateral severe-to-profound sensorineural hearing loss ( single-sided deafness , SSD ) . Study Design IRB-approved , prospect i ve Setting Tertiary center Patients Twenty-nine patients have undergone CI for SSD . SSD was due to Ménière ’s disease ( MD ) in 10 subjects ; these also suffered from recalcitrant vertigo spells and in these 10 patients along with 2 others the CI was placed simultaneous with a labyrinthectomy . Intervention(s ) CI with or without labyrinthectomy . Main Outcome Measure(s ) CNC word and AzBio sentences in quiet were administered to the implanted ear . A multiple-loudspeaker sound localization test was administered in the bilateral listening condition . All data were collected preoperatively and 3 , 6 , and 12 months postoperatively with postoperative data available for 19 subjects . Additionally , a tinnitus h and icap question naire is administered pre- and 12-months post-operatively . Results CNC word and AzBio sentence scores showed improvement in the implanted ear . Sound localization appeared to improve in an experience-dependent fashion in some patients . Most patients reported diminished tinnitus after cochlear implantation . All patients undergoing labyrinthectomy experienced resolution of vertigo attacks . Conclusion CI restores auditory function to the deafened ear . Additionally , the binaural input appears to improve sound localization for most patients . In patients with severe hearing loss and recalcitrant vertigo attacks because of MD , simultaneous labyrinthectomy and CI effectively relieves vertigo attacks and improves auditory function Objective : To evaluate the benefit of a bone-anchored hearing aid contralateral routing of sound hearing aid ( BAHA CROS hearing aid ) in 29 patients with unilateral inner ear deafness . Study Design : Prospect i ve clinical follow-up study . Setting : Tertiary referral center . Patients : Thirty patients were recruited . There were 19 patients with a history of acoustic neuroma surgery and 11 patients with unilateral inner ear deafness due to other causes ; 1 patient was excluded . The first 21 patients had also participated in a previous evaluation . Intervention : Audiometric measurements were taken before intervention , when fitted with a conventional CROS , and after BAHA implementation . Patients ' subjective benefit was quantified with four different hearing aid-specific instruments : the Abbreviated Profile of Hearing Aid Benefit , the Glasgow Hearing Aid Benefit Profile , the International Outcome Inventory for Hearing Aids , and the Single-Sided Deafness question naire . Main Outcome Measures : The same instruments were used at a mean long-term follow-up of 1 year after BAHA implantation . Results : Sound localization in an audiologic test setting was no different from chance level . The main effect of the BAHA CROS that was found was the “ lift the head shadow ” effect in the speech-in-noise measurements . All instruments also showed positive results in favor of the BAHA CROS at long-term follow-up . Conclusions : The poor sound-localization results in an audiologic test setting illustrated the inability of patients with unilateral inner ear deafness to localize sounds . The speech-in-noise measurements demonstrated the efficacy of the BAHA CROS to lift the head shadow . Patients were still satisfied at 1-year follow-up , according to the four instruments Abstract Introduction Severe tinnitus can seriously impair patients in their activities in daily life and reduce their quality of life . The aims of this prospect i ve clinical study were to assess the long-term effects of cochlear implantation ( CI ) on tinnitus in patients with single-sided deafness and ipsilateral incapacitating tinnitus , and to investigate whether CI could treat various types of tinnitus . Material s and methods Twenty-six subjects with unilateral severe-to-profound sensorineural hearing loss received a CI . Patients suffered from severe tinnitus greater than 6/10 on a visual analogue scale ( VAS ) due to unilateral deafness . Assessment consisted of a tinnitus analysis including determination of tinnitus type , frequency , and loudness . A tinnitus question naire ( TQ ) measured tinnitus distress . VAS and TQ were administered pre-implantation and post-implantation . Results All 26 patients reported a subjective benefit from CI . Tinnitus loudness reduced significantly after CI from 8.6 to 2.2 on the VAS ( scale : 0–10 ) . The TQ total score decreased significantly and the mean tinnitus degree decreased from severe to mild . No differences were observed between patients with pure-tone tinnitus , narrow b and noise tinnitus , or polyphonic tinnitus . The degree of tinnitus loudness reduction remained stable after CI . Conclusions CI can successfully be used as treatment of severe tinnitus in patients with single-sided deafness and is equally effective for pure tone , narrow b and noise , and polyphonic tinnitus . Long-term results show that implantation provides durable tinnitus relief in these patients . These results support the hypothesis that physiopathological mechanisms after peripheral deafferentation are reversible when hearing is restored . Single-sided deafness accompanied by severe tinnitus is a new indication for CI Objective : Up to now , treatment modalities of unilateral deafness consist of no treatment , conventional contralateral routing of signal ( CROS ) , or Bone-Anchored Hearing Aid ( BAHA ) hearing aid . Cochlear implantation makes a new treatment modality available for patients with single-sided deafness . The aim of this study is to evaluate the use of unilateral electrical stimulation with normal hearing on the contralateral side after a period of 6 months compared with the preoperative unaided situation , conventional CROS , or BAHA hearing aids . Study Design : Prospect i ve design . Setting : Tertiary referral center ; cochlear implant ( CI ) program . Patients : Eleven adult subjects with unilateral deafness of various causes were enrolled in the study . Only those patients were included in whom therapy with CROS hearing aid or BAHA was not successful and in whom the auditory nerve was found to be intact and the cochlea patent for cochlear implantation . Intervention : All subjects were fitted in r and om order with a BAHA Intenso mounted on the softb and /tension clamp or with a CROS hearing aid . After test periods with both devices , the subjects received a CI . Main Outcome Measures : The Hochmair-Schulz-Moser sentence test and the Oldenburg sentence test were used to test speech comprehension in 3 presentation configurations in the unaided situation , with conventional CROS and BAHA hearing aids before cochlear implantation as well as after 6 months with CI . Localization was assessed using an array of 7 speakers at head level in a frontal semicircle . Subjective improvement in daily life was evaluated using the Speech , Spatial and Qualities of Hearing Scale , the Health Utilities Index 3 and the International Outcome Inventory for Hearing Aids question naires . Tinnitus distress was measured with a tinnitus scale before and after CI implantation . Results : The results show significant improvement in localization ability as well as in speech comprehension in most presentation configurations with the CI . Especially , there is no negative effect on speech comprehension if the noise is presented to the CI ear and speech to the normal hearing ear . With the CI , the summation and squelch effects are not significant , but a significant combined head shadow effect is seen . Speech , Spatial and Qualities of Hearing results show an overall benefit of wearing the CI compared with the other treatment options . The tinnitus scale revealed a positive effect of CI stimulation in cases of preoperative tinnitus . Conclusion : The results in these patients suggest that cochlear implantation improves hearing abilities in people with single-sided deafness and is superior to the alternative treatment options . The use of the CI does not interfere with speech underst and ing in the normal hearing ear . Our data suggest that the binaural integration of electric and acoustic stimulation is possible even with unilateral normal hearing OBJECTIVES : Patients with unilateral hearing loss report difficulty hearing conversation on their impaired side , localizing sound , and underst and ing of speech in background noise . The bone-anchored cochlear stimulator ( BAHA ) ( Entific , Gothenburg , Sweden ) has been shown to improve performance in persons with unilateral severe-profound sensorineural loss ( USNHL ) . The purpose of this study is to evaluate the effectiveness of BAHA in sound localization for USNHL listeners . STUDY DESIGN : Prospect i ve study of 12 USNHL subjects , 9 of whom received implants on the poorer hearing side . A control group of 10 normal hearing subjects were assessed for comparison . Localization with and without BAHA was assessed using an array of 8 speakers at head level separated by 45 degrees . Error analysis matrix was generated to evaluate the confusions , accuracy in response , and laterality judgment . RESULTS : The average accuracy of speaker localization was 16 % in the unaided condition , with no improvement with BAHA use . Laterality judgment was poorer than 43 % in both aided and nonaided conditions . CONCLUSIONS : Patients with UNSNHL had poor sound localization and laterality judgment abilities that did not improve with BAHA use OBJECTIVES : The purpose of this study is to evaluate the effectiveness of Bone Anchored Cochlear Stimulator ( BAHA ) in transcranial routing of signal by implanting the deaf ear . STUDY DESIGN AND SETTING S : Eighteen patients with unilateral deafness were included in a multisite study . They had a 1-month pre-implantation trial with a contralateral routing of signal ( CROS ) hearing aid . Their performance with BAHA was compared with the CROS device using speech reception thresholds , speech recognition performance in noise , and the Abbreviated Profile Hearing Benefit and Single Sided Deafness question naires . RESULTS : Patients reported a significant improvement in speech intelligibility in noise and greater benefit from BAHA compared with CROS hearing aids . Patients were satisfied with the device and its impact on their quality of life . No major complications were reported . CONCLUSION AND SIGNIFICANCE : BAHA is effective in unilateral deafness . Auditory stimuli from the deaf side can be transmitted to the good ear , avoiding the limitations inherent in CROS amplification Objectives We performed an evaluation of the audiological and subjective benefits of the bone-anchored hearing aid ( Baha ) as a device for transcranial routing of sound ( Baha CROS ) in 56 patients with unilateral inner ear deafness . Methods We performed a prospect i ve clinical follow-up study in a tertiary referral center . Previously reported results of 29 patients were supplemented with a second series of 30 patients with unilateral inner ear deafness ; 3 patients dropped out during the evaluation . Audiometric measurements were taken before and after Baha CROS fitting . Subjective benefits were quantified with 4 different patient question naires . Results The sound localization results in a well-structured test setting were not differentiable from chance . The 5 patients with congenital hearing loss showed better scores in the unaided sound localization measurements . Overall , most patients reported some subjective improvement in their capacity to localize sounds with the Baha CROS in daily life . The main effect of the Baha CROS was to alleviate the head shadow effect during the speech-in-noise test . Conclusions Poor sound localization in this larger series of patients confirms the findings of previous studies . Improvements in the speech-in-noise scores corroborated the efficacy of the Baha CROS in alleviating the head shadow effect . The 4 different patient question naires revealed subjective benefit and satisfaction in various domains Objective : To determine the long-term safety and benefit of a new intraoral bone conduction device ( SoundBite Hearing System by Sonitus Medical ) for single-sided deafness ( SSD ) . Study Design : A multi-center , controlled , nonr and omized , prospect i ve unblinded study of SSD patients wearing the device over a 6-month period . Setting s : Ambulatory care centers typical of those where SSD patients are diagnosed and treated . Patients : Adults ( N = 22 ) with acquired , permanent SSD and no current use of any other SSD device . Intervention : Continual daily wear of the new device for 6 months . Main Outcome Measures : Comprehensive medical , audiologic , and dental measures ; aided thresholds ; Abbreviated Profile of Hearing Aid Benefit scores , and an SSD question naire . Results : There were no related adverse events or changes in the medical or audiologic findings at the end of the trial compared with the beginning . There were no significant changes in the mean aided thresholds ( p > 0.01 ) or the mean dental measures ( p > 0.05 ) at 3 or 6 months compared with pretrial measures . The mean Abbreviated Profile of Hearing Aid Benefit benefit scores showed improvement ( p < 0.01 ) for the Background Noise , Reverberation , and Ease of Communication subscales and the Global scale at 3 and 6 months . The results of the SSD question naire indicated that the vast majority ( > 90 % ) of the subjects reported satisfaction and improvement in a variety of areas after wearing the device long term . Conclusion : The SoundBite system is safe and continues to provide substantial benefit for SSD patients with continual daily use over a 6-month period Objective Comparison of the auditory and subjective capabilities of 2 implantable bone conduction devices BAHA Divino Sound Processor ( Divino ) and the BAHA BP100 Sound Processor ( BP100 ) using a daily alternating method . Study Design Open prospect i ve comparative trial . Setting Tertiary referral otology and neurotology center . Patients Ten patients with single-sided deafness ( SSD ) using a Divino for more than 1 year . Interventions The patients with SSD changed to the BP100 for 1 week , and then underwent an evaluation period of 18 days switching between BP100 and Divino on a daily alternating basis . On a scale from 0 to 10 , patients rated their quality of hearing daily with both devices concerning overall satisfaction , clearness of sound , and effort of listening in background noise . For the total duration of the trial , the Spatial Hearing Question naire ( SHQ ) and the Abbreviated Profile of Hearing Aid Benefit ( APHAB ) were administered . In the unaided condition and with Divino at baseline and aided with BP100 after the evaluation period , adaptive speech in quiet and in noise testing was performed with speech and noise coming from different azimuth angles . Main Outcome Measures Subjective rating in a diary , APHAB , SHQ , and aided speech in quiet and speech in noise . Results The diary shows significant improvement on all subscales with BP100 in comparison with Divino . These differences did not change significantly during 18 days . On the APHAB , listening in background noise and in reverberant conditions was rated significantly better with the BP100 . The SHQ shows a significant difference between both devices on all subscales except for source localization and speech underst and ing in quiet . Speech audiometry showed a significant head shadow benefit with both implantable bone conduction devices ( median [ Q1 , Q3 ] : Divino = 2.67 dB [ 0.33 , 1.51 ] , BP100 = 2.83 dB [ 4.08 , 3.83 ] ) . There was no significant difference found between both devices . Conclusion Both the Divino and the BP100 reduce the h and icap experienced by patients with SSD . Subjective assessment using a daily alternating method shows higher overall hearing capabilities with BP100 . Results of the question naires are similar . Speech audiometry in noise does not reveal a statistically significant difference between both devices . A daily alternating method can provide useful information for both the patient and the audiologist because objective measurements do not show any statistically significant differences between patients . In our opinion , daily alternation of devices is a useful method to compare different devices Objective To evaluate and compare the benefit of a bone-anchored hearing implant with 2 different sound processors in adult patients with unilateral severe to profound sensorineural hearing loss ( UHL ) . Study Design Prospect i ve crossover design . Setting Tertiary referral center . Patients Eleven adults with UHL and normal hearing in the contralateral ear were assigned to 2 groups . Intervention All subjects were unilaterally implanted with a bone-anchored hearing implant and were initially fitted with 2 different sound processors ( SP-1 and SP-2 ) . SP-1 is a multichannel device equipped with an omnidirectional microphone and relatively simple digital signal-processing technology and provides a user-adjustable overall gain and tone control with compression limiting . SP-2 is a fully channel-by-channel programmable device , which can be set with nonlinear dynamic range compression or linear amplification . In addition , SP-2 features automatic noise management , an automatic multichannel directional microphone , microphone position compensation , and an implementation of prescription rules for different types of hearing losses , one of them unilateral deafness . After at least 1-month use of the initial processor , both groups were fitted with the alternative processor . Main Outcome Measures Speech discrimination in noise and localization tests were performed at baseline visit before surgery , after at least 1-month use of the initial processor , and after at least 2-week use of the alternative processor . Results Relative to unaided baseline , SP-2 enabled significantly better overall speech discrimination results , whereas there was no overall improvement with SP-1 . There was no difference in speech discrimination between SP-1 and SP-2 in all spatial setting s. Sound localization was comparably poor at baseline and with both processors but significantly better than chance level for all 3 conditions . Conclusion Patients with UHL have an overall objective benefit for speech discrimination in noise using a bone-anchored hearing implant with SP-2 . In contrast , there is no overall objective benefit from SP-1 . Depending on the speech-in-noise presentation setting , the difference between objective benefit from SP-2 and SP-1 might be mainly attributed to the new technological features in SP-2 unavailable in SP-1 such as 1 ) automatic noise management reducing the noise in the speech signal and thus improving the signal-to-noise ratio of the result ing signal on the better ear , 2 ) programmable multichannel sound-processing and nonlinear dynamic range compression offering considerably greater control over signal amplification compared to SP-1 , and 3 ) implementation of a prescription rule for unilateral deafness addressing the specific amplification needs of patients with UHL by reducing amplification in the low frequencies and applying additional gain in the high frequencies . Sound localization is poor but better than chance level in the unaided condition as well as in both bone-anchored hearing system – aided conditions OBJECTIVE To assess the benefits in terms of sound localization , to evaluate speech discrimination in noise , to appraise the prosthesis benefit and to identify outcome in right and left h and ed patients when BAHA are implanted on the right or on the left deaf side . METHODS Two years prospect i ve study in a tertiary referral center . Tests consist on Hearing in Noise Test ( HINT ) and sound localization after 6 months of BAHA use . Quality of life was assessed by the Abbreviated Profile of Hearing Aid Benefit ( APHAB ) question naire . The paired T-test and the analysis of variance were used for the statistical measures . RESULTS Twenty-one subjects participated in this study . HINT : patients score better when speech and noise are spatially separated and noise is not presented to the healthy ear . In the right-h and ed group ( left dominant brain ) , unaided left-implanted patients performed better than right-implanted patient when speech is in front and noise to the good ear ; when speech is presented to the good ear and noise to the front , aided right-implanted patients performed better than aided left-implanted patients . Sound localization : correct answers attain 35 % at best . No statistical difference between the frequencies was found , neither between the left and right implanted patients . APHAB : the score improvement is statistically significant for the global score , the background noise subscale at 5 weeks and for the reverberation subscale at 6 months . CONCLUSION It seems that left dominant hemisphere is able to filter crossed noise better than the right hemisphere . Results of uncrossed speech to the dominant left brain are better than the uncrossed speech to the non-dominant right brain Objective : To analyze the short- , medium- , and long-term benefits from and satisfaction with the Baha for patients with profound unilateral sensorineural hearing loss ( SNHL ) . Design : Prospect i ve clinical study . Setting : Head and Neck Institute at the Clevel and Clinic . Patients : Eight patients with acquired profound unilateral SNHL . Interventions : Patients underwent unaided baseline testing and aided Baha testing using laboratory and self-report measures at 6 postfitting intervals . Main Outcome Measures : Laboratory measures included the revised Speech Perception in Noise test , Hearing in Noise Test , and localization testing . Disease-specific self-report measures included the Abbreviated Profile of Hearing Aid Benefit , Hearing H and icap Inventory for Adults , and Single-Sided Deafness Question naire . The Medical Outcomes Study SF-36 Health Survey was used to assess health-related quality of life . Results : Based on 95 % confidence intervals for unaided testing , significant improvements on aided revised Speech Perception in Noise , Abbreviated Profile of Hearing Aid Benefit , and Hearing H and icap Inventory for Adults scores were sustained during the 18-month test interval . Variable performance was observed for the Hearing in Noise Test over time and patients . No acclimatization effects were shown for localization testing or the generic health-related quality -of-life measure . Patients reported satisfaction in a variety of situations as quantified by the Single-Sided Deafness Question naire in the long-term . Conclusion : The Baha is effective in reducing psychosocial consequences of unilateral profound SNHL for the long-term . Improvement in speech underst and ing occurred when the primary signal was spatially separated from background noise . Localization performance did not improve with Baha use . Overall , patients were satisfied with their Baha and would still elect to have this procedure if given a second chance Cochlear implantation ( CI ) is a new form of treatment in the rehabilitation of single-sided deafness . The patient requires thorough initial examination and a full explanation of alternative treatment options prior to determining the indication for CI treatment . To date , we have treated 28 patients with CI , of whom data are available for 11 after 12 months . We examined speech comprehension in background noise and localisation ability 12 months after CI implantation compared to conventional CROS ( contralateral routing of signal ) hearing aids , BAHA ( bone-anchored hearing aid ) and hearing in untreated patients . In addition , we determined the subjective h and icap ( HHIE , hearing h and icap inventory for the elderly ) and the subjective success ( IOI-HA , international outcome inventory for hearing aids ; SSQ , spatial and qualities of hearing scale ) of each treatment option . After 12 months ' experience , the results show a significantly better localisation ability and an improvement in speech comprehension in background noise with CI than with the other treatment options . Subjective results also show a clear benefit with CI . Careful patient selection is a decisive factor for successful treatment of this patient group . Under these conditions , CI is a treatment option with which significant improvement in speech comprehension and localization ability in single-sided deafness is possible OBJECTIVES /HYPOTHESIS Determine the benefit of the bone-anchored hearing aid ( BAHA ) in patients with unilateral deafness . STUDY DESIGN Retrospective case series and prospect i ve question naire study at a tertiary referral center . METHODS Patients with unilateral deafness of various etiologies who were implanted with a BAHA ( n = 126 ) or not implanted with a BAHA after a translabyrinthine craniotomy ( n = 126 ) were mailed question naires . A total of 139 patients ( 55 % ) responded to the question naires . Patients who were implanted with a BAHA received a general question naire concerning BAHA usage , the Abbreviated Profile of Hearing Aid Benefit ( APHAB ) , and the Speech , Spatial , and Qualities of Hearing Question naire ( SSQ ) . Patients not implanted with a BAHA received only the SSQ hearing question naire . RESULTS Patients with unilateral deafness demonstrated a benefit with BAHA use on the APHAB . Most improvement with the BAHA was seen in the Background Noise subscale , with a 17.4 % improvement . Ease of Communication and Reverberation subscales also demonstrated an 11.6 % and 13.2 % benefit , respectively . Patients with a BAHA demonstrated better scores in the SSQ Speech subscale when compared to unilaterally deaf patients who did not have a BAHA , although this difference was not significant . CONCLUSIONS The APHAB demonstrated significant benefit with the use of a BAHA in patients with unilateral deafness . Although the SSQ speech subscale showed overall improvement in auditory disability with the use of a BAHA , this difference was not significant . However , the SSQ hearing question naire demonstrated specific situations were the BAHA is most useful BACKGROUND The Baha implant is increasingly becoming a common form of treatment for individuals with single-sided deafness ( SSD ) . However , evidence -based guidelines for determining c and idacy in these patients are not yet established . PURPOSE The purpose of this study was to investigate the clinical utility of speech-in-noise testing as a part of the preoperative evaluation of the Baha device in patients with SSD . RESEARCH DESIGN The study design was a prospect i ve cohort of 24 English-speaking adults comparing preoperative results on speech-in-noise measures using the Baha Cordelle II headb and stimulator to postoperative results using the patient 's external Baha processor . INTERVENTION Outcome measures included signal-to-noise ratio ( SNR ) loss as measured by the QuickSIN ™ and scores of self-reported disability question naires . RESULTS Wilcoxon signed-rank test result ed in no significant difference between the preoperative and postoperative methods for measuring benefit on listening in noise tasks . Passing Bablok regression analysis showed the preoperative and postoperative results to be statistically equivalent , which suggests that postoperative results can be predicted during preoperative testing . Wilcoxon signed-rank test showed significant improvements in self-reported disability postoperatively . CONCLUSIONS The results support the use of speech-in-noise measures as an accurate predictor of overall benefit in patients with SSD prior to implantation |
1,673 | 25,490,697 | However , studies do not clarify the degree to which changes in mindfulness are a mechanism responsible for weight loss in mindfulness interventions . | OBJECTIVE Mindfulness training has been incorporated increasingly into weight loss programs to facilitate dietary and physical activity changes .
This systematic review of studies using mindfulness-based programs for weight loss evaluated study method ologies with the goal of determining the current evidence in support of mindfulness interventions for weight loss . | To explore the efficacy of a mindfulness-based weight loss intervention for women . Sixty-two women ( ages 19 - 64 ; BMI 22.5 - 52.1 ) who were attempting to lose weight were r and omised to an intervention or control condition . The former were invited to attend four 2-h workshops , the latter were asked to continue with their normal diets . Data were collected at baseline , 4 and 6 months . BMI , physical activity , mental health . At 6 months intervention participants showed significantly greater increases in physical activity compared to controls ( p<.05 ) but no significant differences in weight loss or mental health . However , when intervention participants who reported ' never ' applying the workshop principles at 6 months ( n=7 ) were excluded , results showed both significantly greater increases in physical activity ( 3.1 sessions per week relative to controls , p<.05 ) and significantly greater reductions in BMI ( 0.96 relative to controls , equivalent to 2.32 kg , p<0.5 ) . Reductions in BMI were mediated primarily by reductions in binge eating . Despite its brevity , the intervention was successful at bringing about change . Further refinements should increase its efficacy Psychological distress and elevated cortisol secretion promote abdominal fat , a feature of the Metabolic Syndrome . Effects of stress reduction interventions on abdominal fat are unknown . Forty-seven overweight/obese women ( mean BMI = 31.2 ) were r and omly assigned to a 4-month intervention or waitlist group to explore effects of a mindfulness program for stress eating . We assessed mindfulness , psychological distress , eating behavior , weight , cortisol awakening response ( CAR ) , and abdominal fat ( by dual-energy X-ray absorptiometry ) pre- and posttreatment . Treatment participants improved in mindfulness , anxiety , and external-based eating compared to control participants . Groups did not differ on average CAR , weight , or abdominal fat over time . However , obese treatment participants showed significant reductions in CAR and maintained body weight , while obese control participants had stable CAR and gained weight . Improvements in mindfulness , chronic stress , and CAR were associated with reductions in abdominal fat . This proof of concept study suggests that mindfulness training shows promise for improving eating patterns and the CAR , which may reduce abdominal fat over time Background Obesity is a growing epidemic . Weight control interventions can achieve weight loss , but most is regained over time . Stigma and low quality of life are significant problems that are rarely targeted . Purpose A new model aim ed at reducing avoidant behavior and increasing psychological flexibility , has shown to be relevant in the treatment of other chronic health problems and is worth examining for improving the lives of obese persons . Methods Patients who had completed at least 6 months of a weight loss program ( N = 84 ) were r and omly assigned to receive a 1-day , mindfulness and acceptance-based workshop targeting obesity-related stigma and psychological distress or be placed on a waiting list . Results At a 3-month follow-up , workshop participants showed greater improvements in obesity-related stigma , quality of life , psychological distress , and body mass , as well as improvements in distress tolerance , and both general and weight-specific acceptance and psychological flexibility . Effects on distress , stigma , and quality of life were above and beyond the effects due to improved weight control . Mediational analyses indicated that changes in weight-specific acceptance coping and psychological flexibility mediated changes in outcomes . Conclusion Results provide preliminary support for the role of acceptance and mindfulness in improving the quality of life of obese individuals while simultaneously augmenting their weight control efforts The present study utilized an analog paradigm to investigate the effectiveness of two strategies for coping with food cravings , which was theorized to be critical to the maintenance of weight loss . Ninety-eight undergraduate students were given transparent boxes of chocolate Hershey 's Kisses and instructed to keep the chocolates with them , but not to eat them , for 48 h. Before receiving the Kisses , participants were r and omized to receive either ( a ) no intervention , ( b ) instruction in control-based coping strategies such as distraction and cognitive restructuring , or ( c ) instruction in acceptance-based strategies such as experiential acceptance and defusion techniques . Measures included the Power of Food Scale ( PFS ; a measure of psychological sensitivity to the food environment ) , self-report ratings of chocolate cravings and surreptitiously recorded chocolate consumption . Results suggested that the effect of the intervention depended on baseline PFS levels , such that acceptance-based strategies were associated with better outcomes ( cravings , consumption ) among those reporting the highest susceptibility to the presence of food , but greater cravings among those who scored lowest on the PFS . It was observed that craving self-report measures predicted chocolate consumption , and baseline PFS levels predicted both cravings and consumption . Results are discussed in terms of the implication s for weight loss maintenance strategies Objective To determine whether acceptance-based behavioral treatment ( ABT ) would result in greater weight loss than st and ard behavioral treatment ( SBT ) , and whether treatment effects were moderated by interventionist expertise or participants ’ susceptibility to eating cues . Recent research suggests that poor long-term weight control outcomes are due to lapses in adherence to weight control behaviors , and that adherence might be improved by enhancing SBT with acceptance-based behavioral strategies . Design and Methods Overweight participants ( n = 128 ) were r and omly assigned to 40 weeks of SBT or ABT . Results Both groups produced significant weight loss and , when administered by experts , weight loss was significantly higher in ABT than SBT at post-treatment ( 13.17 % v. 7.54 % ) and 6-month follow-up ( 10.98 % v. 4.83 % ) . Moreover , 64 % of those receiving ABT from experts ( v. 46 % for SBT ) maintained at least a 10 % weight loss by follow-up . Moderation analyses revealed a powerful advantage , at follow-up , of ABT over SBT in those potentially more susceptible to eating cues . For participants with greater baseline depression symptomology , weight loss at follow-up was 11.18 % in ABT vs. 4.63 % in SBT ; other comparisons were 10.51 % vs. 6.00 % ( emotional eating ) , 8.29 % v. 6.35 % ( disinhibition ) and 9.70 % v. 4.46 % ( responsivity to food cues ) . Mediation analyses produced partial support for theorized food-related psychological acceptance as a mechanism of action . Conclusions Results offer strong support for the incorporation of acceptance-based skills into behavioral weight loss treatments , particularly among those with greater levels of depression , responsivity to the food environment , disinhibition and emotional eating , and especially when interventions are provided by weight control experts . Trial Registration clinical trials.gov identifier : Most of the extant literature investigating the health effects of mindfulness interventions relies on wait-list control comparisons . The current article specifies and vali date s an active control condition , the Health Enhancement Program ( HEP ) , thus providing the foundation necessary for rigorous investigations of the relative efficacy of Mindfulness Based Stress Reduction ( MBSR ) and for testing mindfulness as an active ingredient . 63 participants were r and omized to either MBSR ( n = 31 ) or HEP ( n = 32 ) . Compared to HEP , MBSR led to reductions in thermal pain ratings in the mindfulness- but not the HEP-related instruction condition ( η(2 ) = .18 ) . There were significant improvements over time for general distress ( η(2 ) = .09 ) , anxiety ( η(2 ) = .08 ) , hostility ( η(2 ) = .07 ) , and medical symptoms ( η(2 ) = .14 ) , but no effects of intervention . Practice was not related to change . HEP is an active control condition for MBSR while remaining inert to mindfulness . These cl aims are supported by results from a pain task . Participant-reported outcomes ( PROs ) replicate previous improvements to well-being in MBSR , but indicate that MBSR is no more effective than a rigorous active control in improving these indices . These results emphasize the importance of using an active control condition like HEP in studies evaluating the effectiveness of MBSR Mindful eating may be an effective intervention for increasing awareness of hunger and satiety cues , improving eating regulation and dietary patterns , reducing symptoms of depression and anxiety , and promoting weight loss . Diabetes self-management education ( DSME ) , which addresses knowledge , self-efficacy , and outcome expectations for improving food choices , also may be an effective intervention for diabetes self-care . Yet few studies have compared the impact of mindful eating to a DSME-based treatment approach on patient outcomes . Adults 35 to 65 years old with type 2 diabetes for ≥1 year not requiring insulin therapy were recruited from the community and r and omly assigned to treatment group . The impact of a group-based 3-month mindful eating intervention ( MB-EAT-D ; n = 27 ) to a group-based 3-month DSME “ Smart Choices ” ( SC ) intervention ( n = 25 ) postintervention and at 3-month follow-up was evaluated . Repeated- measures ANOVA with contrast analysis compared change in outcomes across time . There was no significant difference between groups in weight change . Significant improvement in depressive symptoms , outcome expectations , nutrition and eating-related self-efficacy , and cognitive control and disinhibition of control regarding eating behaviors occurred for both groups ( all p < .0125 ) at 3-month follow-up . The SC group had greater increase in nutrition knowledge and self-efficacy than the MB-EAT-D group ( all p < .05 ) at 3-month follow-up . MB-EAT-D had significant increase in mindfulness , whereas the SC group had significant increase in fruit and vegetable consumption at study end ( all p < .0125 ) . Both SC and MB-EAT-D were effective treatments for diabetes self-management . The availability of mindful eating and DSME-based approaches offers patients greater choices in meeting their self-care needs OBJECTIVES The purpose of this study was to pilot a brief ( 6-week ) group curriculum for providing mindfulness training to obese individuals , called Mindful Eating and Living ( MEAL ) . SETTING AND DESIGN Participants were recruited through a local Young Men 's Christian Association ( YMCA ) in spring 2006 . Data was collected at three time points : baseline , completion of intervention ( 6 weeks ) , and 3-month follow-up ( 12 weeks ) . INTERVENTION Six weekly two-hour group classes ( with two monthly follow-up classes ) . Content included training in mindfulness meditation , mindful eating , and group discussion , with emphasis on awareness of body sensations , emotions , and triggers to overeat . MAIN OUTCOME MEASURES Key variables assessed included changes in weight , body-mass index ( BMI ) , eating behavior , and psychological distress . In addition , physiological markers of cardiovascular risk were evaluated including C-reactive protein ( hsCRP ) , adiponectin , low-density lipoprotein ( LDL ) , and plasminogen activator inhibitor-1 ( PAI-1 ) . RESULTS Ten obese patients enrolled with a mean BMI of 36.9 kg/m² [ SD±6.2 ] . The mean weight was 101 kg/m² and the mean age was 44 years ( SD=8.7 ; range=31 - 62 ) . Compared to baseline data , participants showed statistically significant increases in measures of mindfulness and cognitive restraint around eating , and statistically significant decreases in weight , eating disinhibition , binge eating , depression , perceived stress , physical symptoms , negative affect , and C-reactive protein . CONCLUSIONS This study provides preliminary evidence that a eating focused mindfulness-based intervention can result in significant changes in weight , eating behavior , and psychological distress in obese individuals Recent research has identified that mindfulness meditation in group setting s supports people who are trying to lose weight . The present research investigated mindfulness meditation in group and individual setting s , and explored the potential impact on weight loss and other factors ( i.e. mindfulness , impulsivity , and avoidance ) that may assist or hinder weight loss . Specifically , the hypotheses tested were that the group setting assisted dieters more than the individual setting by reducing weight , cognitive-behavioral avoidance , and impulsivity and by increasing mindfulness . Participants ( n = 170 ) who were trying to lose weight were r and omly assigned to practice meditation for 6 weeks within a group or independently . Measurements in mindfulness , cognitive-behavioral avoidance , impulsivity , and weight occurred twice ( pre- and post-intervention ) . Results indicated that participants in the group setting lost weight and lowered their levels of cognitive-behavioral avoidance , while impulsivity and mindfulness remained stable . On the other h and , participants in the individual condition lost less weight , while there was an increase in cognitive-behavioral avoidance and mindfulness scores , but a decrease in impulsivity . Seeing that benefits and limitations observed in group setting s are not replicated when people meditate alone , this study concluded that mindfulness meditation in individual setting s needs to be used with caution , although there are some potential benefits that could aid future weight loss research |
1,674 | 23,156,969 | Only limited evidence indicated that LLLT is more effective than placebo , sham laser , and other active treatments | Abstract The aim of this study was to assess the effectiveness of low level laser therapy ( LLLT ) as a treatment for orofacial pain considering the methodology of the studies . | We present a double-blind trial in which a pulsed infrared beam was compared with a placebo in the treatment of myofascial pain in the cervical region . The patients were su bmi tted to 12 sessions on alternate days to a total energy dose of 5 J each . At each session , the four most painful muscular trigger points and five bilateral homometameric acupuncture points were irradiated . Those in the placebo group su bmi tted to the same number of sessions following an identical procedure , the only difference being that the laser apparatus was nonoperational . Pain was monitored using the Italian version of the McGill pain question naire and the Scott-Huskisson visual analogue scale . The results show a pain attenuation in the treated group and a statistically significant difference between the two groups of patients , both at the end of therapy and at the 3-month follow-up examination OBJECTIVE We aim ed to evaluate the effectiveness of laser therapy in myofascial pain syndrome treatment . BACKGROUND DATA Myofascial pain syndrome is a disease that is characterized by hypersensitive points called trigger points found in one or more muscles and /or connective tissues . It can cause pain , muscle spasm , sensitivity , stiffness , weakness , limitation of range of motion and rarely autonomic dysfunction . Physical therapy modalities and exercise are used in the treatment of this frequently encountered disease . METHODS The placebo controlled , prospect i ve , long-term follow up study was planned with 60 patients who had trigger points in their upper trapezius muscles . The patients were divided into three groups r and omly . Stretching exercises were taught to each group and they were asked to exercise at home . Treatment duration was 4 weeks . Placebo laser was applied to group 1 , dry needling to group 2 and laser to group 3 . He-Ne laser was applied to three trigger points in the upper trapezius muscles on both sides with 632.8 nm . The patients were assessed at before , post-treatment , and 6 months after-treatment for pain , cervical range of motion and functional status . RESULTS We observed a significant decrease in pain at rest , at activity , and increase in pain threshold in the laser group compared to other groups . Improvement according to Nottingham Health Profile gave the superiority of the laser treatment . However , those differences among the groups were not observed at 6-month follow up . CONCLUSIONS Laser therapy could be useful as a treatment modality in myofascial pain syndrome because of its noninvasiveness , ease , and short-term application UNLABELLED The dentin hypersensitivity is a painful condition rather prevalent in the general population . There are several ways of treatment for such condition , including the low intensity lasers . The proposal of this study was to verify the effectiveness of the Gallium-Aluminum-Arsenide diode laser in the treatment of this painful condition , using a placebo as control . MATERIAL S AND METHODS Thirty-two patients were selected , 22 females and 10 males , with ages ranging from 20 to 52 years old . The 32 patients were r and omly distributed into two groups , treated and control ; the sample consisted of 68 teeth , 35 in the treated group and 33 in the control group . The treated group was exposed to six laser applications with intervals from 48 to 72 hours , and the control group received , as placebo , applications of a curing light . RESULTS A significant reduction was observed in the pain condition between the initial phase and after six laser applications ; however , such reduction could also be observed for the control group exposed to the placebo . CONCLUSION Therapy with the low intensity Gallium-Aluminum-Arsenide laser - AsGaAl induces a statistically significant reduction in the painful condition after each application and between the beginning and end of treatment , although there was no statistically significant difference between the treated group ( laser ) and the control group ( placebo ) at the end of treatment and after the mediate evaluation results ( after 6 weeks ) , this way impairing the real measurement of laser effectiveness and placebo effect Objective : To investigate the effectiveness of low‐level laser therapy in the treatment of temporom and ibular disorder and to compare treatment effects in myogenic and arthrogenic cases . Methods : Thirty‐five patients were evaluated by magnetic resonance imaging and r and omly allocated to active treatment ( n=20 ) and placebo treatment ( n=15 ) groups . In addition to a daily exercise program , all patients were treated with fifteen sessions of low‐level laser therapy . Pain , joint motion , number of joint sounds and tender points were assessed . Results : Significant reduction in pain was observed in both active and placebo treatment groups . Active and passive maximum mouth opening , lateral motion , number of tender points were significantly improved only in the active treatment group . Treatment effects in myogenic and arthrogenic cases were similar . Conclusion : Low‐level laser therapy can be considered as an alternative physical modality in the management of temporom and ibular disorder The aim of the study was to evaluate the effect of low level laser application on postoperative pain after endodontic surgery in a double blind , r and omized clinical study . Fifty-two healthy adults undergoing endodontic surgery were included into the study . Subsequently to suturing , 26 patients had the operation site treated with an 809 nm-GaAlAs-laser ( oralaser voxx , Oralia GmbH , Konstanz , Germany ) at a power output of 50 mW and an irradiation time of 150 s. Laser treatment was simulated in further 26 patients . Patients were instructed to evaluate their postoperative pain on 7 days after surgery by means of a visual analogue scale ( VAS ) . The results revealed that the pain level in the laser group was lower than in the placebo group throughout the 7 day follow-up period . The differences , however , were significant only on the first postoperative day ( Mann-Whitney U-test , p<0.05 ) . Low level laser therapy can be beneficial for the reduction of postoperative pain . Its clinical efficiency and applicability with regard to endodontic surgery , however require further investigation . This is in particular true for the optimal energy dosage and the number of laser treatments needed after surgery Low-energy laser therapy has been applied in several rheumatoid and soft tissue disorders with varying rates of success . The objective of our study was to investigate the effect of laser therapy on cervical myofascial pain syndrome with a placebo-controlled double-blind prospect i ve study model . It was performed with a total of 53 patients ( 35 females and 18 males ) with cervical myofascial pain syndrome . In group 1 ( n=23 ) , GaAs laser treatment was applied over three trigger points bilaterally and also one point in the taut b and s in trapezius muscle bilaterally with a frequency of 1000 Hz for 2 min over each point once a day for 10 days during a period of 2 weeks . In group 2 ( n=25 ) , the same treatment protocol was given , but the laser instrument was switched off during applications . All patients in both groups were instructed to perform daily isometric exercises and stretching just short of pain for 2 weeks at home . Evaluations were performed just before treatment ( week 0 ) , immediately after ( week 2 ) , and 12 weeks later ( week 14 ) . Evaluation parameters included pain , algometric measurements , and cervical lateral flexion . Statistical analysis was done on data collected from three evaluation stages . The results were evaluated in 48 patients ( 32 females , 16 males ) . Week 2 and week 14 results showed significant improvement in all parameters for both groups . However , comparison of the percentage changes both immediately and 12 weeks after treatment did not show a significant difference relative to pretreatment values . In conclusion , the results of our study have not shown the superiority of GaAs laser therapy over placebo in the treatment of cervical myofascial pain syndrome , but we suggest that further studies on this topic be done using different laser types and dosages in larger patient population BACKGROUND AND OBJECTIVES The efficacy of low level laser therapy ( LLLT ) in myofascial pain syndrome ( MPS ) seems controversial . Our aim was to clarify the effect of LLLT in MPS by using algometry and thermography . STUDY DESIGN / MATERIAL S AND METHODS Sixty-two patients with MPS having an active trigger point in the neck or upper back region were r and omly divided into two equal groups according to therapy applied ( group 1 : LLLT + stretching exercises , group 2 : stretching exercises alone ) . The outcome measures were pain measured with visual analogue scale ( VAS ) , algometry on the trigger point , algometric difference , thermographic difference , and thermal asymmetry . Comparison was made within and between the groups pre- and post-therapeutically and 3 weeks after therapy . RESULTS Mean pain values decreased more significantly in group 1 from baseline to 3 weeks follow up ( 7.54 - 3.06 ) while these values were 7.03 - 5.19 in group 2 ( P < 0.05 ) . Group comparisons revealed significant favorable differences in group 1 patients in terms of all other parameters at the first and the second evaluation post therapeutically ( P < 0.05 ) . CONCLUSIONS LLLT seemed to be beneficial for pain in MPS by using algometry and thermography BACKGROUND AND OBJECTIVES A prospect i ve , double-blind , r and omized , and controlled trial was conducted in patients with chronic myofascial pain syndrome ( MPS ) in the neck to evaluate the effects of infrared low level 904 nm Gallium-Arsenide ( Ga-As ) laser therapy ( LLLT ) on clinical and quality of life ( QoL ) . STUDY DESIGN / PATIENTS AND METHODS The study group consisted of 60 MPS patients . Patients were r and omly assigned to two treatment groups : Group I ( actual laser ; 30 patients ) and Group II ( placebo laser ; 30 patients ) . LLLT continued daily for 2 weeks except weekends . Follow-up measures were evaluated at baseline , 2 , 3 , and 12 weeks . All patients were evaluated with respect to pain at rest , pain at movement , number of trigger points ( TP ) , the Neck Pain and Disability Visual Analog Scale ( NPAD ) , Beck depression Inventory ( BDI ) , and the Nottingham Health Profile ( NHP ) . RESULTS In active laser group , statistically significant improvements were detected in all outcome measures compared with baseline ( P < 0.01 ) while in the placebo laser group , significant improvements were detected in only pain score at rest at the 1 week later of the end of treatment . The score for self-assessed improvement of pain was significantly different between the active and placebo laser groups ( 63 vs. 19 % ) ( P < 0.01 ) . CONCLUSION This study revealed that short-period application of LLLT is effective in pain relief and in the improvement of functional ability and QoL in patients with MPS Cervical dentine hypersensitivity is the most frequent complaint among reported odontalgias . Thus , this study evaluated the effectiveness of two types of lasers ( 660 nm wavelength red , and 830 nm wavelength infrared ) as dentine desensitizers , as well as both the immediate and late therapeutic effects in individuals 25 to 45 years of age . A total of 40 teeth with cervical exposure were treated in 4 sessions . They were divided into 2 groups according to treatment . A 660 nm wavelength red diode laser and an 830 nm wavelength infrared diode laser were used . Dentine sensitivity to cold nociceptive stimulus was evaluated by means of a pain numeric scale from zero to 10 before each treatment session , at 15 and 30 min after irradiation , and in a follow-up period of 15 , 30 and 60 days after the end of treatment . Significant levels of dentinal desensitization were only found in patients ranging in age from 25 to 35 years . The 660 nm red diode laser was more effective than the 830 nm infrared laser and a higher level of desensitization was observed at the 15 and 30 minute post-irradiation examinations . The immediate and late therapeutic effects of the 660 nm red diode laser were more evident in 25 - 35-year-old patients compared with those of the 830 nm infrared diode laser , in terms of the different age groups The efficacy of low-level laser therapy ( LLLT ) in myofascial pain syndrome ( MPS ) seems controversial . A prospect i ve , double-blind , r and omized controlled trial was conducted in patients with chronic MPS in the neck to evaluate the effects of low-level 830-nm gallium arsenide aluminum ( Ga – As – Al ) laser therapy . The study group consisted of 64 MPS patients . The patients were r and omly assigned into two groups . In group 1 ( n = 32 ) , Ga – As – Al laser treatment was applied over three trigger points bilaterally for 2 min over each point once a day for 15 days during a period of 3 weeks . In group 2 ( n = 32 ) , the same treatment protocol was given , but the laser instrument was switched off during applications . All patients in both groups performed daily isometric exercise and stretching exercises for cervical region . Parameters were measured at baseline and after 4 weeks . All patients were evaluated with respect to pain ( at rest , movement , and night ) and assessed by visual analog scale , measurement of active range of motion using an inclinometer and a goniometer , and the neck disability index . In both groups , statistically significant improvements were detected in all outcome measures compared with baseline ( p < 0.05 ) . However , no significant differences were obtained between the two groups ( p > 0.05 ) . In conclusion , although the laser therapy has no superiority over placebo groups in this study , we can not exclude the possibility of effectivity with another treatment regimen including different laser wavelengths and dosages ( different intensity and density and /or treatment interval ) OBJECTIVE To compare the clinical efficacy of the GaAlAs laser and dentin bonding agent in treating dentin hypersensitivity . METHODS One hundred and forty teeth from 70 patients diagnosed with dentin hypersensitivity , were divided into two groups : In group I , teeth were irradiated with 30 mW GaAlAs laser for 1 min and in group II , teeth were applied with dentin bonding agent . Sensitivity was assessed by tactile and thermal tests , measured with the criteria proposed by Uchida at baseline and after treatment ; immediately , at 15 and at 30 days . RESULTS The reduction of dentin hypersensitivity was observed in both treatments using the GaAlAs laser and dentin bonding agent . However , a greater reduction was observed over time up to day 15 and no significant change was observed between days 15 and 30 . Statistically significant differences in the level of dentin hypersensitivity between bonding agent and the GaAlAs laser were found at each observation period ( p < 0.05 ) . CONCLUSION The GaAlAs laser had less desensitizing efficacy compared with dentin bonding agent . However , the desensitizing effect of the GaAlAs laser still could be considered an effective therapy for treating dentin hypersensitivity This study aim ed to evaluate the effectiveness of low intensity laser therapy ( LILT ) in 30 patients presenting temporom and ibular joint ( TMJ ) pain and m and ibular dysfunction in a r and om and double-blind research design . The sample , divided into experimental group ( 1 ) and placebo group ( 2 ) , was su bmi tted to the treatment with infrared laser ( 780 nm , 30 mW , 10 s , 6.3 J/cm(2 ) ) at three TMJ points . The treatment was evaluated throughout six sessions and 15 , 30 and 60 days after the end of the therapy , through visual analogue scale ( VAS ) , range of m and ibular movements and TMJ pressure pain threshold . The results showed a reduction in VAS ( p < 0.001 ) and through the ANOVA with repeated measures it was observed that the groups did not present statistically significant differences ( P = 0.2060 ) , as the averages of the evaluation times ( P = 0.3955 ) and the interaction groups evaluation times ( P = 0.3024 ) , considering the MVO . The same occurred for RLE ( P = 0.2988 , P = 0.1762 and P = 0.7970 ) , LLE ( P = 0.3265 , P = 0.4143 and P = 0.0696 ) , PPTD ( P = 0.1558 , P = 0.4695 and P = 0.0737 ) and PPTE ( P = 0.2376 , P = 0.3203 and P = 0.0624 ) . For PE , there were not statistically significant differences for groups ( P = 0.7017 ) and the interaction groups evaluation times ( P = 0.6678 ) , even so in both groups the PE varied with time ( P = 0.0069 ) AIMS To evaluate the effectiveness of low-level laser therapy ( LLLT ) in patients presenting with temporom and ibular disorder ( TMD ) in a r and om and placebo-controlled research design . METHODS The sample consisted of 40 patients , divided into an experimental group ( G1 ) and a placebo group ( G2 ) . The treatment was done with an infrared laser ( 830 nm , 500mW , 20s , 4J/point ) at the painful points , once a week for four consecutive weeks . The patients were evaluated before and after the treatment through a Visual Analogue Scale ( VAS ) and the Craniom and ibular Index ( CMI ) . RESULTS The baseline and posttherapy values of VAS and CMI were compared by the paired T-test , separately for the placebo and laser groups . A significant difference was observed between initial and final values ( p < 0.05 ) in both groups . Baseline and post-therapy values of pain and CMI were compared in the therapy groups by the two- sample T-test , yet no significant differences were observed regarding VAS and CMI ( p > 0.05 ) . CONCLUSION After either placebo or laser therapy , pain and temporom and ibular symptoms were significantly lower , although there was no significant difference between groups . The low-level laser therapy was not effective in the treatment of TMD , when compared to the placebo OBJECTIVES This study evaluated the immediate and 3 month clinical effects of a low-level gallium-aluminum-arsenide ( GaAlAs ) laser and a 3 % potassium oxalate gel for the treatment of dentinal hypersensitivity . MATERIAL S AND METHODS A total of 164 teeth from 30 patients with clinical diagnoses of dentinal hypersensitivity were selected for this r and omized , placebo-controlled , double-blind clinical study . The teeth were r and omized to three groups : GaAlAs laser , oxalate gel , and placebo gel . The treatment sessions were performed at 7 d intervals for four consecutive weeks . The degree of sensitivity in response to an air blast and tactile stimuli was assessed according to a visual analogue scale at baseline , immediately after the fourth application , and then 3 months after the fourth application . The reductions in dentinal hypersensitivity from baseline at the two follow-up assessment s were evaluated as the main outcome . RESULTS In both the active and control groups , there were statistically significant reductions in dentinal hypersensitivity immediately after and 3 months after the treatments , when compared with the hypersensitivity at baseline . No significant differences among the three groups could be detected in their efficacy at either the immediate or 3 month evaluations irrespective of the stimulus . CONCLUSIONS The treatments under study were effective for reducing dentinal hypersensitivity , and longer observational periods could enhance the ability of studies to detect differences between active and placebo groups The aim of this paper was to evaluate the efficacy of a Low-Level Laser therapy in patients with Temporom and ibular Disorders ( TMD ) using a double-blind design . A sample of 20 patients with a chief complaint of pain was divided into myogenous and arthrogenous groups . The sample was also divided on the basis of the treatment rendered : real versus placebo treatment . An 830 nm Ga-Al-As Laser device with a energy power of 4 joules was used ( OMNILASE , LASERDYNE PTY LTD . ) in three treatment sessions . To evaluate the effectiveness of laser treatment , a Visual Analogue Scale ( VAS ) was used for pain and active range of motion ( AROM ) was used to measure changes in m and ibular function . Using real laser treatment , the author found that there was a reported improvement in pain only for the myogenous pain patients ( p < or = 0.02 ) . For the arthrogenous pain patients , real laser treatment result ed in an improvement in Total Vertical Opening ( TVO ) ( p < 0.05 ) , Protrusive excursion ( PROT ) ( p < 0.02 ) and Left lateral excursion ( LATLEF ) ( p < 0.02 ) . The placebo control group showed improvement in TVO and PROT for those patients having myogenous pain and LATLEF for those patients having arthrogenous pain . A repeated measurement one-way ANOVA demonstrated no significant differences between real and placebo groups . Considering the non-invasive and harmless characteristics of this modality , more research is recommended , using higher power and increased frequency of laser applications One possible cause of the reported positive treatment effect by low‐power laser exposure in muscle pain conditions could be that it increases the local microcirculation . The aim of this study was therefore to investigate the immediate effects on masseter muscle blood flow by low‐power laser exposure in patients with chronic orofacial pain of muscular origin in comparison to healthy individuals . Twelve patients with myofascial pain of orofacial muscles and 12 age and gender matched healthy individuals participated in the study . Before laser exposure the subjects were examined clinical ly and the patients scored their current pain intensity from the most tender masseter muscle . Intramuscular laser‐Doppler flowmetry was performed unilaterally in the most tender point ( patients ) or in a st and ardized point ( healthy subjects ) of the masseter muscle . The muscle was first exposed with a Gallium – Aluminum – Arsenide laser ( active laser ) or placebo laser for 2 min in a r and omized and double‐blind manner . After another 8 min the muscle was treated with the other laser for 2 min and the LDF recording continued for 8 min . Finally , the patients again assessed the pain intensity . Data were analyzed blindly by one of the authors not participating in data collection . The pain intensity was not affected by laser exposure . The blood flow did not change significantly in the patients , but increased after active laser exposure and decreased after placebo exposure in the healthy individuals . The difference between active laser and placebo was significant . In conclusion , the results of this study do not support an effect of low‐power laser exposure on masseter muscle microcirculation in patients with chronic orofacial pain of muscular origin Myofacial pain dysfunction syndrome ( MPDS ) is the most common reason for pain and limited function of the masticatory system . The effects of low-level lasers ( LLLs ) for controlling the discomfort of patients are investigated frequently . However , the aim of this study was to evaluate the efficacy of a particular source producing 660 nm and 890 nm wavelengths that was recommended to reduce of the pain in the masticatory muscles . This was a double-blind and placebo-controlled trial . Sixteen MPDS patients were r and omly divided into two groups . For the laser group , two diode laser probes ( 660 nm ( nanometers ) , 6.2 J/cm2 , 6 min , continuous wave , and 890 nm , 1 J/cm2 ( joules per square centimetre ) , 10 min , 1,500 Hz ( Hertz ) ) were used on the painful muscles . For the control group , the treatment was similar , but the patients were not irradiated . Treatment was given twice a week for 3 weeks . The amount of patient pain was recorded at four time periods ( before and immediately after treatment , 1 week after , and on the day of complete pain relief ) . A visual analog scale ( VAS ) was selected as the method of pain measurement . Repeated- measures analysis of variance ( ANOVA ) , the t-test and the paired t-test were used to analyze the data . In each group the reduction of pain before and after the treatment was meaningful , but , between the two groups , low-level laser therapy ( LLLT ) was more effective ( P = 0.031 ) According to this study , this type of LLLT was the effective treatment for pain reduction in MPDS patients A comparative double blind study testing low level laser therapy ( Gallium/Aluminium/Arsenide laser [ GaAlAs ] ) against placebo was carried out in the management of dentinal tooth hypersensitivity . Subjects demonstrating dentinal hypersensitivity and complying with strict selection criteria were r and omly assigned to an active and placebo group . Low level laser therapy was applied for one minute to both the apex and cervical area of the tooth ; and reapplied at one week , two-week and eight-week intervals . Dentinal hypersensitivity was rated at each visit . There were 28 subjects in the placebo group and 22 and 21 subjects , respectively , in the tactile sensitivity and thermal sensitivity groups . Comparisons between the groups were conducted using independent groups t-test . In both the tactile and thermal sensitivity groups differences between the active and placebo groups were significant from the first week and increased further in the second and eighth weeks . The mean value of thermal sensitivity decreased 67 per cent ( p < 0.001 ) compared with placebo ( 17 per cent ) and tactile sensitivity decreased 65 per cent ( p = .002 ) compared with placebo ( 21 per cent ) at eight weeks . Results demonstrate that the GaAlAs laser is an effective method for the treatment of both thermal and tactile dentinal hypersensitivity . There were no reported adverse reactions or instances of oral irritation Temporom and ibular joint pain dysfunction syndrome ( TMJPDS ) comprises of a constellation of signs and symptoms including joint tenderness and pain on function , restricted jaw movement , clicking , jaw locking and tenderness in the muscles of mastication . Headache may also be a feature . Physiotherapy is commonly employed in the treatment of this condition but there is little published material reporting the relative efficacy of the different types of treatment currently available . Further , no attempt seems to have been made to compare the costs of physiotherapy with other forms of treatment of this disorder such as occlusal splint therapy . This paper reports a comparative evaluation of four different physiotherapy treatments and placebo in the management of TMJPDS and comments on their cost benefit aspects compared with that of splint therapy . The four methods of physiotherapy tested were short-wave diathermy , megapulse , ultrasound and soft laser . There was no statistically significant difference in success rate between any of the four tested ( range 70.4–77.7 % ) although each individually was significantly better than placebo treatment . The time of improvement appeared to vary between the four The effect of helium-neon ( He-Ne ) laser on the prevention of pain , swelling and trismus following the removal of an impacted third molar was studied in 100 patients r and omly allocated to receive He-Ne laser , ibuprofen or placebo in a prospect i ve double-blind parallel clinical trial . Trismus was significantly reduced in the He-Ne laser and ibuprofen treatment groups . Pain was significantly less in the ibuprofen group with regard to He-Ne laser and placebo groups . Swelling was the same in the three treatment groups Abstract Limited studies have demonstrated that low intensity laser therapy ( LILT ) may have a therapeutic effect on the treatment of myofascial pain syndrome ( MPS ) . Sixty ( 60 ) patients with MPS and having one active trigger point in the anterior masseter and anterior temporal muscles were selected and assigned r and omly to six groups ( n=10 ) : Groups I to III were treated with GaAlAS ( 780 nm ) laser , applied in continuous mode and in a meticulous way , twice a week , for four weeks . Energy was set to 25 J/cm2 , 60 J/cm2 and 105 J/cm2 , respectively . Groups IV to VI were treated with placebo applications , simulating the same parameters as the treated groups . Pain scores were assessed just before , then immediately after the fourth application , immediately after the eighth application , at 15 days and one month following treatment . A significant pain reduction was observed over time ( p<0.001 ) . The analgesic effect of the LILT was similar to the placebo groups . Using the parameters described in this experiment , LILT was effective in reducing pain experienced by patients with myofascial pain syndrome . Thus , it was not possible to establish a treatment protocol . Analyzing the analgesic effect of LILT suggests it as a possible treatment of MPS and may help to establish a clinical protocol for this therapeutic modality OBJECTIVE The purpose of this study was to assess the effectiveness of low-level laser therapy ( LLLT ) in the treatment of myogenic originated temporom and ibular disorders ( TMD ) . BACKGROUND DATA Limited studies have demonstrated that LLLT may have a therapeutic effect on the treatment of TMD . METHODS Thirty-nine patients with myogenic TMD-associated orofacial pain , limited m and ibular movements , chewing difficulties , and tender points were included in this study . Twenty-four of them were treated with LLLT for 10 sessions per day excluding weekends as test group , and 15 patients with the same protocol received placebo laser treatment as a control group . These parameters were assessed just before , just after , and 1 month after the treatment . RESULTS Maximal mouth-opening improvement , and reductions in pain and chewing difficulty were statistically significant in the test group when compared with the control group . Statistically significant improvements were also detected between two groups regarding reduction in the number of tender points . CONCLUSION Based on the results of this placebo-controlled report , LLLT is an appropriate treatment for TMD and should be considered as an alternative to other methods Abstract The purpose of this study was to evaluate the effectiveness of low intensity laser therapy ( LILT ) for the control of pain from temporom and ibular disorder ( TMD ) in a r and om and double-blind research design . Forty-eight ( 48 ) patients presenting temporom and ibular joint ( TMJ ) pain were divided into an experimental group ( GI ) and a placebo group ( GII ) . The sample was su bmi tted to the treatment with infrared laser ( 780 nm , 70 mW , 10 s , 89.7 J/cm2 ) applied in continuous mode on the affected temporom and ibular region , at one point : inside the external auditive duct toward the retrodiskal region , twice a week , for four weeks . For the control group , two identical probes ( one active and one that does not emit radiation ) were used unknown by the clinician and the subjects . A tip planned for laser acupuncture was used and connected to the active point of the probe . The parameter evaluated was the intensity of pain after palpation of the condylar lateral pole , pre-auricular region and external auditive duct , according to the Visual Analogue Scale ( VAS ) . Four evaluations were performed : Ev1 ( before laser application ) , Ev2 ( after 4th application ) , Ev3 ( after 8th application ) and Ev4 ( 30 days after the last application ) . Data were su bmi tted to statistical analysis . The results showed a decrease in the pain level mainly for the active probe . Among the evaluations , the Ev3 exhibited lower sensitivity to palpation . In conclusion , the results show that low intensity laser is an effective therapy for the pain control of subjects with TMD The aim of this study was to evaluate in vivo the use of low-level galium-aluminium-arsenide ( GaAlAs ) ( BDP 600 ) laser and sodium fluoride varnish ( Duraphat ) in the treatment of cervical dentine hypersensitivity . Twelve patients , with at least two sensitive teeth were selected . A total of 60 teeth were included in the trial . Prior to desensitizing treatment , dentine hypersensitivity was assessed by a thermal stimulus and patients ' response to the examination was considered to be a control . The GaAlAs laser ( 15 mW , 4 J/cm2 ) was irradiated on contact mode and fluoride varnish was applied at cervical region . The efficiency of the treatments was assessed at three examination periods : immediately after first application , 15 and 30 days after the first application . The degree of sensitivity was determined following predefined criteria . Data were su bmi tted to analysis and no statistically significant difference was observed between fluoride varnish and laser . Considering the treatments separately , there was no significant difference for the fluoride varnish at the three examination periods , and for laser therapy , significant difference ( P < 0.05 ) was found solely between the values obtained before the treatment and 30 days after the first application . It may be concluded that both treatments may be effective in decreasing cervical dentinal hypersensitivity . Moreover , the low-level GaAlAs laser showed improved results for treating teeth with higher degree of sensitivity OBJECTIVE The objective of this study was to assess the effectiveness of low-level laser therapy ( LLLT ) in the management of temporom and ibular joint ( TMJ ) pain in a r and om and double-blind research design . STUDY DESIGN TMJ pain patients , r and omly assigned , received 2 to 3 treatments per week for 8 weeks of active LLLT ( Helium Neon , 632.8 nm , 30 mW ) ( n = 26 ) or sham LLLT ( n = 26 ) . Measures of TMJ pain during function were evaluated at baseline and weeks 2 , 4 , and 8 after the first laser therapy . RESULTS At the 8-week point , within-group improvements were present for TMJ pain during function , for both the active and sham LLLT groups ( P = .000 ) . Between-group differences were not highly evident ( P > .05 ) . CONCLUSION The study suggests that LLLT is not better than placebo at reducing TMJ pain during function OBJECTIVE The aim of this study was to evaluate the effectiveness of low-level laser therapy ( LLLT ) and transcutaneous electrical neural stimulation ( TENS ) on the improvement of mouth opening in patients with temporom and ibular disorder ( TMD ) . BACKGROUND DATA TMDs are conditions that affect the form and /or function of the temporom and ibular joint ( TMJ ) , masticatory muscles , and dental apparatus . Often TMD is associated with pain localized in the TMJ and /or in the muscles of the face and neck . METHODS This clinical trial was performed in 10 patients , 18 - 56 years old , diagnosed with TMD of multiple causes . All patients received both methods of treatment in two consecutive weeks . LLLT was delivered via a 670-nm diode laser , output power 50 mW , fluence 3 J per site/4 sites ( masseter muscle , temporal muscle , m and ibular condyle , and intrauricular ) . TENS therapy was applied with a two-electrode machine at 20 W , maximum frequency of 60 Hz , adjusted by the patient according to their sensitivity . The amplitude of mouth opening was recorded before treatment and immediately after using a millimeter rule ; the measurements were performed from the incisal of the upper incisors to the incisal of the lower incisors . A paired t-test was applied to verify the significance of the results . RESULTS A significant improvement in the range of motion for both therapies was observed immediately after treatment . Comparing the two methods , the values obtained after LLLT were significantly higher than those obtained after TENS ( p < 0.01 ) . CONCLUSIONS Both methods are effective to improve mouth opening . Comparing the two methods , LLLT was more effective than TENS applications Abstract The purpose of this study was to evaluate the analgesic effect of Low Intensity Laser Therapy ( LILT ) and its influence on masticatory efficiency in patients with temporom and ibular dysfunction ( TMD ) . This study was performed using a r and om , placebo-controlled , and double-blind research design . Fourteen patients were selected and divided into two groups ( active and placebo ) . Infrared laser ( 780 nm , 70 mw , 60s , 105J/cm2 ) was applied precisely and continuously into five points of the temporom and ibular joint ( TMJ ) area : lateral point ( LP ) , superior point ( SP ) , anterior point ( AP ) , posterior point ( PP ) , and posterior-inferior point ( PIP ) of the condylar position . This was performed twice per week , for a total of eight sessions . To ensure a double-blind study , two identical probes supplied by the manufacturer were used : one for the active laser and one for the inactive placebo laser . They were marked with different letters ( A and B ) by a clinician who did not perform the applications . A Visual Analogue Scale ( VAS ) and a colorimetric capsule method were employed . Data were obtained three times : before treatment ( Ev1 ) , shortly after the eighth session ( Ev2 ) , and 30 days after the first application ( Ev3 ) . Statistical tests revealed significant differences at one percent ( 1 % ) likelihood , which implies that superiority of the active group offered considerable TMJ pain improvement . Both groups presented similar masticatory behavior , and no statistical differences were found . With regard to the evaluation session , Ev2 presented the lowest symptoms and highest masticatory efficiency throughout therapy . Therefore , low intensity laser application is effective in reducing TMD symptoms , and has influence over masticatory efficiency [ Ev2 ( 0.2423 ) and Ev3 ( 0.2043 ) , observed in the interaction Evaluations x Probes for effective dosage ] OBJECTIVE Low-level laser therapy ( LLLT ) treatment for pain caused by temporom and ibular joint disorders ( TMD ) was investigated in a controlled study comparing applied energy density , subgroups of TMD , and duration of disorders . BACKGROUND DATA Although LLLT is a physical therapy used in the treatment of musculoskeletal disorders , there is little evidence for its effectiveness in the treatment of TMD . METHODS The study group of 61 patients was treated with 10 J/cm(2 ) or 15 J/cm(2 ) , and the control group of 19 patients was treated with 0.1 J/cm(2 ) . LLLT was performed by a GaAlAs diode laser with output of 400 mW emitting radiation wavelength of 830 nm in 10 sessions . The probe with aperture 0.2 cm(2 ) was placed over the painful muscle spots in the patients with myofascial pain . In patients with TMD arthralgia the probe was placed behind , in front of , and above the m and ibular condyle , and into the meatus acusticus externus . Changes in pain were evaluated by self-administered question naire . RESULTS Application of 10 J/cm(2 ) or 15 J/cm(2 ) was significantly more effective in reducing pain compared to placebo , but there were no significant differences between the energy densities used in the study group and between patients with myofascial pain and temporom and ibular joint arthralgia . Results were marked in those with chronic pain . CONCLUSION The results suggest that LLLT ( application of 10 J/cm(2 ) and 15 J/cm(2 ) ) can be considered as a useful method for the treatment of TMD-related pain , especially long lasting pain |
1,675 | 17,347,960 | Calcimimetics used in patients receiving haemodialysis or peritoneal dialysis are more effective than placebo in controlling secondary hyperparathyroidism ( reduced parathyroid hormone levels , calcium levels and phosphorus levels ) .
All phosphate binders are effective in controlling hyperphosphatemia but different doses are to be used with different agents to achieve similar targets .
Dosing needs to be adjusted according to phosphorus levels .
Vitamin D and its analogues are recommended in CKD patients , although there is no significant evidence of superiority of individual agents in head-to-head comparisons .
Available evidence suggests that calcimimetics , phosphate binders and vitamin D or its analogues are effective in the treatment of secondary hyperparathyroidism . | BACKGROUND The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic review s ( SR ) of r and omized trials ( RCT ) or RCT data only .
In the present guideline , evidence of the use of calcimimetics , phosphate binders , vitamin D and vitamin D analogues for treating secondary hyperparathyroidism in chronic kidney disease ( CKD ) is presented . | The i.v . bolus administration of 1 alpha hydroxylated vitamin D derivatives is effective in the treatment of uremic hyperparathyroidism . However , few of the published studies of this mode of treatment have been adequately controlled , and recent reports have suggested that p.o . bolus administration may be just as effective . In this study , 16 hemodialysis patients with mild to moderate hyperparathyroidism were assigned , after a 4-wk run-in period , to receive a 6-wk course of either thrice-weekly i.v . or p.o . alfacalcidol ( initial dose , 4 micrograms ) . Then , after a further control period , they received a second 6-wk course , with either p.o . or i.v . alfacalcidol ( whichever was not given in the first treatment period ) . Plasma parathyroid hormone ( PTH ) was measured weekly by the use of an intact hormone assay . Both routes of therapy result ed in a significant suppression of plasma PTH ( P = 0.005 ) and an elevation in plasma ionized calcium ( P = 0.01 ) . The magnitude of the responses was similar for the two treatment phases , as was the relationship between the increment in calcium and the decrement in PTH . The most complete suppression of PTH was seen in those with the greatest increment in plasma calcium . The incidence of hypercalcemia and the mean dose reductions necessary were also similar in the two treatment phases . Oral bolus therapy and i.v . bolus therapy with alfacalcidol are equally effective in suppressing hyperparathyroidism . The postulated advantages of i.v . over p.o . therapy with 1 alpha hydroxylated vitamin D derivatives remain to be confirmed by controlled studies Thirteen patients in the predialysis phase of chronic renal failure ( CRF ) were treated with calcitriol ( 0.25 micrograms/day ) and 12 with placebo . After 1 year of study , an increase in bone mineral density in the calcitriol group measured by dual-energy X-ray absorptiometry was seen for the femoral neck and lumbar spine when compared to the placebo group ( p < 0.001 and p < 0.01 , respectively ) . We conclude that a steady low dose of calcitriol started in the predialysis phase of CRF is beneficial to the patients with CRF . This may be partly due to suppression of secondary hyperparathyroidism Our prospect i ve 1-year study comprises 93 patients of both sexes , various ages and various dialysis duration . Among them , 31 patients with a concentration of Ca in blood under 2.7 mmol/l , a concentration of P under 1.8 mmol/l and a concentration of PTHi over 65 pg/ml ( group 0 ) received calcitriol 0.25 microgramx418p4The control group consisted of patients not receiving calcitriol and having normal Ca and P metabolism ( group 1 ) . The rest of the patients had a concentration of P over 1.8 mmol/l and could not be given calcitriol . A comparison of the dynamics of average plasmic concentrations of Ca , P , AP , PTHi and X-ray changes in group 0 and 1 at the beginning of the investigation and 1 year later was carried out . At the termination of the 1-year treatment , when compared to the initial state , a statistically significant increase in the concentration of Ca ( p < 0.005 ) and in the concentration of P ( p < 0.005 ) was noted in group 0 . The average concentration of PTHi decreased to the desired level , the X-ray changes characteristic of secondary hyperparathyroidism progressed more slowly in group 0 BACKGROUND Intermittent oral or intravenous doses of calcitriol given two or three times per week are commonly used to treat secondary hyperparathyroidism ( secondary HPT ) . This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal ( i.p . ) versus oral doses of calcitriol in children with secondary HPT undergoing peritoneal dialysis ( CCPD ) . METHODS Forty-six patients aged 12.5+/-4.8 years on CCPD for 22+/-25 months were r and omly assigned to treatment with oral ( p.o . ) or i.p . calcitriol for 12 months ; 17 subjects given p.o . calcitriol and 16 subjects given i.p . calcitriol completed the study . Bone biopsies were performed at the beginning and at the end of the study , while determinations of serum and total ionized calcium , phosphorus , alkaline phosphatase , parathyroid hormone ( PTH ) and calcitriol levels were done monthly . RESULTS Serum total and ionized calcium levels were higher in subjects treated with i.p . calcitriol , P < 0.0001 , whereas serum phosphorus levels were higher in those given p.o . calcitriol , P < 0.0001 . For the i.p . group , serum PTH levels decreased from pre-treatment values of 648+/-125 pg/ml to a nadir of 169+/-57 pg/ml after nine months . In contrast , serum PTH levels did not change from baseline values of 670+/-97 pg/ml in subjects given p.o . calcitriol , P < 0.0001 by multiple regression analysis . Serum alkaline phosphatase levels were also lower in patients treated with i.p . calcitriol , P < 0.0001 , but there was no difference between groups in the average dose of calcitriol given thrice weekly . The skeletal lesions of secondary HPT improved in both groups , 33 % of patients developed adynamic bone lesion . CONCLUSION Differences in the bioavailability of calcitriol and /or in phosphorus metabolism may account for the divergent biochemical response to p.o . and i.p . calcitriol Management of secondary hyperparathyroidism is challenging with traditional therapy . The calcimimetic cinacalcet HCl acts on the calcium-sensing receptor to increase its sensitivity to calcium , thereby reducing parathyroid hormone ( PTH ) secretion . This phase 3 , multicenter , r and omized , placebo-controlled , double-blind study evaluated the efficacy and safety of cinacalcet in hemodialysis ( HD ) and peritoneal dialysis ( PD ) patients with PTH > or = 300 pg/ml despite traditional therapy . A total of 395 patients received once-daily oral cinacalcet ( 260 HD , 34 PD ) or placebo ( 89 HD , 12 PD ) titrated from 30 to 180 mg to achieve a target intact PTH ( iPTH ) level of < or = 250 pg/ml . During a 10-wk efficacy assessment phase , cinacalcet was more effective than control for PTH reduction outcomes , including proportion of patients with mean iPTH levels < or = 300 pg/ml ( 46 versus 9 % ) , proportion of patients with > or = 30 % reduction in iPTH from baseline ( 65 versus 13 % ) , and proportion of patients with > or = 20 , > or = 40 , or > or = 50 % reduction from baseline . Cinacalcet had comparable efficacy in HD and PD patients ; 50 % of PD patients achieved a mean iPTH < or = 300 pg/ml . Cinacalcet also significantly reduced serum calcium , phosphorus , and Ca x P levels compared with control treatment . The most common side effects , nausea and vomiting , were usually mild to moderate in severity and transient . Once-daily oral cinacalcet was effective in rapidly and safely reducing PTH , Ca x P , calcium , and phosphorus levels in patients who received HD or PD . Cinacalcet offers a new therapeutic option for controlling secondary hyperparathyroidism in patients with chronic kidney disease on dialysis BACKGROUND Calcium-based phosphate binders may induce tissue calcification , and little is known about their effects on bone density . We compared the effects of a calcium with a non-calcium phosphate binder on both arterial calcification and bone density measured by computed tomography . METHODS Seventy-two adult haemodialysis patients were r and omized to treatment with calcium carbonate ( CC ) or sevelamer ( SEV ) for 2 years . Electron beam CT scans were performed at baseline and at 6 , 12 and 24 months . Serum phosphorus , calcium , calcium x phosphorus product and intact parathyroid hormone ( iPTH ) were measured and other routine laboratory tests were also carried out . RESULTS The average calcium x phosphorus product was similar in the two treatment groups . However , patients receiving CC had significantly lower average iPTH ( P<0.01 ) , were more likely to have hypercalcaemic episodes ( P = 0.03 ) and had significantly greater increases in coronary artery ( CC median 484 , P<0.0001 , SEV median 37 , P = 0.3118 , between-group P = 0.0178 ) and aortic ( CC median 610 , P = 0.0003 , SEV median 0 , P = 0.5966 , between-group P = 0.0039 ) calcification scores . The CC group also had a significant decrease in trabecular bone density ( CC median -6 % , P = 0.0049 , SEV median + 3 % , P = 0.0296 , between-group P = 0.0025 ) . However , there was no significant difference in cortical bone density between the two groups . CONCLUSIONS This 2 year study shows that calcium carbonate use is continuously associated with progressive arterial calcification in haemodialysis patients . In addition , it suggests that it is also associated with decreased trabecular bone density . However , this latter finding requires confirmation by a study specifically devoted to this issue Controversy exists among various studies in regard to the efficacy of oral ( p.o . ) versus parenteral calcitriol . Some studies suggest that intravenous ( i.v . ) calcitriol is superior to p.o . calcitriol for treating renal osteodystrophy in hemodialysis patients ; others suggest that these routes of administration are equivalent . To our knowledge , no large , prospect i ve , r and omized study compares intraperitoneal ( i.p . ) to p.o . calcitriol in adult peritoneal dialysis patients . We conducted a prospect i ve r and omized study in 76 patients ( 38 on i.p . calcitriol and 38 on p.o . calcitriol ) , whom we followed for 48 months . Of the 76 patients , 34 ( 18 in the i.p . group and 16 in the p.o . group ) completed the 48-month study period . Calcitriol dosing was similar in both groups ( 3 - 6 micrograms per week in three divided doses ) . Dose adjustments were made depending on levels of parathyroid hormone ( PTH ) , serum calcium , phosphorus , and calcitriol . No significant difference was seen between the groups in regard to age , sex , race , body mass index , dialysis duration , or cause of ESRD . Neither was any difference in the incidence of peritonitis seen between the groups . In the first 3 - 6 months , PTH decreased equivalently in both groups . The PTH level remained suppressed in the i.p . group throughout the remainder of the study , but , in the p.o . group , PTH returned to its pretreatment level after 3 - 6 months . Mean serum calcium was not different in the two groups . In the p.o . group , a considerably higher mean follow-up phosphorus level ( 6.8 + /- 2.3 mg/dL versus 4.7 + /- 1.4 mg/dL , p = 0.008 ) , PTH level ( 384 + /- 146 pg/mL versus 162 + /- 64 pg/mL ; p = 0.005 ) , and alkaline phosphatase level ( 178 + /- 37 IU/L versus 72 + /- 21 IU/L , p = 0.02 ) were seen as compared to the i.p . group . In the i.p . group , resolution of osteodystrophy occurred in all patients at the end of the study ; in the p.o . group , 5 patients maintained or developed osteodystrophy by the end of the study ( p = 0.016 ) . We conclude that i.p . calcitriol is more effective than pulse p.o . calcitriol in lowering PTH and alkaline phosphatase levels and in resolving renal osteodystrophy , and that i.p . calcitriol is associated with a lower incidence of hyperphosphatemia and elevated Ca x PO4 byproduct BACKGROUND Higher doses of calcitriol are effective in lowering markedly elevated 1,84 PTH levels of patients with renal secondary hyperparathyroidism . It has not been established , however , whether prophylactic administration of low doses of calcitriol prevents an increase of 1,84 PTH without causing side-effects , i.e. hypercalcaemia , hypercalciuria , or hyperphosphataemia . STUDY DESIGN We carried out a placebo-controlled , double-blind prospect i ve multicentre trial over 12 months in 45 patients with mild to moderate renal failure . Criteria for inclusion were S-creatinine 1.4 mg/dl and 1,84 PTH > 6 pmol/l ( normal 6 ) . Calcitriol 0.125 microgram/day per os was compared with placebo . The patients received calcium carbonate per os if serum P exceeded 1.7 mmol/l . RESULTS Baseline 1,84 iPTH concentrations were not significantly different , i.e. 14.0 pmol/l ( 6.7 - 63.3 ) on placebo vs 16.2 ( 6.85 - 82.0 ) on calcitriol . Intention to treat analysis revealed a significant difference of final 1,84 iPTH , i.e. 27.8 ( 4.2 - 68.5 ) on placebo vs 18.2 ( 4.45 - 75.5 ) on calcitriol . On post-hoc analysis the difference was even more pronounced at S-creatinine concentrations above 3 mg/dl . S-calcium , S-phosphate , and urinary excretion of calcium did not change significantly on either placebo or on calcitriol . There were no episodes of hypercalcaemia or hyperphosphataemia . There was no significant difference of final S-creatinine or change in S-creatinine between placebo and calcitriol . One patient on calcitriol and two on placebo progressed to terminal renal failure . Bone alkaline phosphatase as a non-invasive index of bone metabolism was not decreased to subnormal levels . CONCLUSION The results document that a therapeutic window exists in patients with moderate renal failure and elevated of 1,84 iPTH , where low-dose calcitriol ( 0.125 microgram/day ) prevents the increase in 1,84 iPTH without causing side-effects . This observation suggests that the parathyroid is more sensitive to calcitriol than intestine and bone BACKGROUND Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients . So far , it has been evaluated only in patients receiving calcitriol , without comparison with CaCO(3 ) alone , although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3 ) in suppressing parathyroid hormone ( PTH ) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate . Moreover , this bile salt binder may decrease serum 25-OH vitamin D. Therefore , we compared for 5 months two strategies for controlling moderate hyperparathyroidism : CaCO(3 ) alone vs sevelamer in conjunction with measures to increase calcium balance . METHODS Forty-two patients were r and omized : 21 continued their treatment with 4.8 g/day CaCO(3 ) and 21 were switched to sevelamer ( initial dose : 2.4 g/day , increased to 4.4 g/day ) . Each month , when serum-corrected calcium decreased below 2.30 mmol/l , dialysate calcium was increased or alphacalcidol was given at each dialysis session , according to serum PO(4 ) levels . The following parameters were monitored : serum Ca , PO(4 ) , bicarbonate and protein , weekly ; and serum PTH , 25-OH vitamin D and total , LDL and HDL cholesterol monthly . RESULTS Except for higher serum phosphate at month 1 , lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group , no difference was found between the two groups . Compared with baseline levels , PTH increased and 25-OH vitamin D decreased significantly in both groups , these two parameters being inversely correlated . CONCLUSIONS Given comparable control of plasma calcium , phosphate and 25-OH vitamin D , PTH control is comparable in both strategies . Sevelamer does not induce greater vitamin D depletion than CaCO(3 ) . The transient decrease of serum bicarbonate after discontinuation of CaCO(3 ) in the sevelamer group suggests a less optimal prevention of acidosis . The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention Treatment with vitamin D sterols can lower plasma parathyroid hormone ( PTH ) in many patients with secondary hyperparathyroidism due to end-stage renal disease , but hypercalcemia , hyperphosphatemia , or both often develop during treatment . As such , alternative therapeutic approaches to managing excess PTH secretion are needed . Calcimimetic agents directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid gl and s , but clinical experience with them is limited . Fifty-two hemodialysis patients with secondary hyperparathyroidism were given single orally administered doses of the calcimimetic agent AMG 073 ranging from 5 to 100 mg , or placebo . Plasma PTH levels decreased 2 h after 25- , 50- , 75- , or 100-mg doses , falling by a maximum of 43 + /- 29 % , 40 + /- 36 % , 54 + /- 28 % , or 55 + /- 39 % , respectively . Plasma PTH levels decreased in all patients given doses of > or = 25 mg but did not change in those who received placebo . In patients treated with daily doses of 25 or 50 mg of AMG 073 for 8 d , plasma PTH levels declined for the first 3 to 4 d and remained below baseline values after 8 d of treatment . Serum calcium concentrations also decreased by 5 to 10 % from pretreatment levels in patients given 50 mg of AMG 073 for 8 d , but values were unchanged in those who received lower doses . Serum phosphorus levels and values for the calcium-phosphorus ion product both decreased after treatment with AMG 073 . Thus , 8 d of treatment with AMG 073 effectively lowers plasma PTH levels and improves several disturbances in mineral metabolism that have been associated with soft tissue and vascular calcification and with adverse cardiovascular outcomes in patients with end-stage renal disease BACKGROUND Patients with secondary hyperparathyroidism often require therapy that provides long-term control of parathyroid hormone concentrations without increasing calcium and phosphorus concentrations . Cinacalcet modulates the calcium-sensing receptor on the parathyroid gl and to reduce secretion of parathyroid hormone and lower serum calcium , phosphorus and calcium-phosphorus product in haemodialysis patients . METHODS Dialysis patients with secondary hyperparathyroidism [ parathyroid hormone ( PTH ) level > or = 300 pg/ml ] who were enrolled in one of four phase 2 placebo-controlled studies were eligible to enroll in an open-label extension study in which all patients received cinacalcet . For this extension study , cinacalcet was initiated at 30 mg in all patients and the dose was escalated to a maximum of 180 mg once daily if PTH concentrations were > 250 pg/ml . Use of concomitant vitamin D sterols and phosphate binders was not restricted . RESULTS The analysis of all patients ( n = 59 ) completing 100 weeks of cinacalcet treatment showed long-term control of PTH and calcium-phosphorus product . Approximately 55 % achieved a PTH concentration < or = 300 pg/ml at the week-100 study visit , and approximately 60 % had at least a 30 % reduction in PTH from baseline . Serum calcium , phosphorus and the calcium-phosphorus product did not increase during the study . Concomitant vitamin D sterol and phosphate binder therapy remained stable . Cinacalcet was safe and generally well tolerated at doses up to 180 mg/day . CONCLUSIONS In this long-term study , cinacalcet effectively sustained reductions in PTH for up to 3 years without increasing concentrations of serum calcium , phosphorus or calcium-phosphorus product BACKGROUND To identify differences between the effects of calcitriol and the calcitriol analogue , maxacalcitol , on parathyroid hormone ( PTH ) and bone metabolisms , we conducted a r and omized prospect i ve multicentre study on patients on chronic haemodialysis . METHODS We r and omly assigned 91 patients with secondary hyperparathyroidism [ intact PTH ( iPTH ) > or = 150 pg/ml ] to have either calcitriol ( 47 patients ) or maxacalcitol ( 44 patients ) therapy , for 12 months after a 1 month control period . Serum electrolytes , bone alkaline phosphatase ( bAP ) , iPTH , total PTH and PTH(1 - 84 ) ( whole PTH ) levels were measured periodically . The first end point was a serum iPTH of < 150 pg/ml , the second was the iPTH levels obtained . RESULTS Treatment was discontinued for various reasons in nine patients in each group , but no serious side effects were observed in either group . The numbers of cases reaching the first end point were not significantly different between the two groups . Serum calcium concentration was significantly higher in the maxacalcitol than the calcitriol group during early treatment , but not at the end of treatment . Throughout the treatment period there were no significant differences between the two groups in serum iPTH , inorganic phosphate , the product of the serum calcium and inorganic phosphorus concentrations , bAP , or the ratio of whole PTH to total PTH minus whole PTH . Nor were the changes in these parameters significantly different between the two groups comparing the patients with moderate to severe hyperparathyroidism ( basal iPTH > or = 500 pg/ml ) . CONCLUSION Calcitriol and maxacalcitol are equally effective on PTH and bone metabolism BACKGROUND Treatment of persistent hyperparathyroidism in renal transplant patients resistant to calcium and vitamin D sterols is limited and often requires parathyroidectomy . Given the potential hazards linked to surgery , an alternative approach to manage excess parathyroid hormone ( PTH ) secretion is needed . Calcimimetics inhibit PTH secretion by modulating the calcium-sensing receptor in the parathyroid . Lowering of the serum calcium concentration with the calcimimetic cinacalcet has previously been demonstrated in patients with primary hyperparathyroidism or with secondary hyperparathyroidism on dialysis . Here we present the first clinical observations of a calcimimetic in patients with persistent hyperparathyroidism . METHODS A 30 mg dose of cinacalcet was prescribed once daily for 3 months to seven female and seven male stable renal transplant patients , aged 23 - 65 years , 7 months to 14 years after transplantation , with a serum creatinine ranging from 89 to 229 micromol/l and persistent hyperparathyroidism . Concomitant medication included cyclosporin and low-dose prednisone in all patients . RESULTS On cinacalcet , serum calcium decreased and normalized in all but two patients ( baseline 2.72+/-0.03 mmol/l ; 1 month 2.42+/-0.04 mmol/l , P<0.001 ) , whereas serum PTH and phosphate levels did not change significantly . A slight reduction in renal function , as assessed by serum creatinine concentration , was observed at months 2 and 3 ( P<0.05 ) . An immunoglobulin-deficient patient developed colitis after 1 week of treatment and cinacalcet was withdrawn . No patient stopped cinacalcet because of other presumed side effects . CONCLUSION Calcimimetics are a promising therapy in renal transplant patients with persistent hyperparathyroidism . Prospect i ve controlled studies must now be design ed focusing on functionally relevant musculo-skeletal end-points and allowing the exclusion of negative effects on long-term renal and general outcome of such patients Background : We recently determined that in hemodialysis patients , the use of calcium salts to correct hyperphosphatemia led to progressive coronary artery and aortic calcification as determined by sequential electron beam tomography ( EBT ) while the use of the non-calcium-containing binder sevelamer did not . Whether the specific calcium preparation ( acetate vs. carbonate ) might influence the likelihood of progressive calcification was debated . Methods : To determine whether treatment with calcium acetate was specifically associated with hypercalcemia and progressive vascular calcification , we conducted an analysis restricted to 108 hemodialysis patients r and omized to calcium acetate or sevelamer and followed for one year . Results : The reduction in serum phosphorus was roughly equivalent with both agents ( calcium acetate –2.5 ± 1.8 mg/dl vs. sevelamer –2.8 ± 2.0 mg/dl , p = 0.53 ) . Subjects given calcium acetate were more likely to develop hypercalcemia ( defined as an albumin-corrected serum calcium ≧10.5 mg/dl ) ( 36 vs. 13 % , p = 0.015 ) . Treatment with calcium acetate ( mean 4.6 ± 2.1 g/day – equivalent to 1.2 ± 0.5 g of elemental calcium ) led to a significant increase in EBT-determined calcification of the coronary arteries ( mean change 182 ± 350 , median change + 20 , p = 0.002 ) and aorta ( mean change 181 ± 855 , median change + 73 , p < 0.0001 ) . These changes were similar in magnitude to those seen with calcium carbonate . There were no significant changes in calcification among sevelamer-treated subjects . Conclusion : Despite purported differences in safety and efficacy relative to calcium carbonate , calcium acetate led to hypercalcemia and progressive vascular calcification in hemodialysis patients BACKGROUND The bone abnormalities that lead to symptomatic renal osteodystrophy commence early in the course of renal failure , but the optimal time to start treatment needs clarifying . The present study examined the effect of alfacalcidol treatment on bone metabolism and bone density in patients with pre-dialysis chronic renal failure ( CRF ) in a prospect i ve , r and omized , placebo-controlled double blind design . METHODS Repetitive measures of bone mineral density ( BMD ) estimated by dual energy X-ray absorptiometry and plasma levels of biochemical markers of bone turnover [ osteocalcin , bone alkaline phosphatase , propeptide of type-I collagen ( PICP ) and telopeptide of type-I collagen ] and parameters of calcium homeostasis were performed in 36 patients with a glomerular filtration rate ( GFR ) of 6 - 60 ml/min . RESULTS A significant difference in BMD between the treatment groups in favour of the alfacalcidol-treated patients was found in the spine ( 4.2 % ) , the femoral neck ( 4.9 % ) and the total femur ( 3.0 % ) ( P<0.05 ) . In the alfacalcidol group , plasma levels of parathyroid hormone 1 - 84 decreased from baseline values by 47+/-9 % , and p-osteocalcin and bone alkaline phosphatase decreased by 24+/-9 % and 48+/-8 % , respectively ( P<0.05 ) . In the placebo group , PICP increased by 32+/-26 % ( P<0.05 ) . No significant changes were found in plasma levels of vitamin D metabolites . GFR decreased significantly from baseline values in the alfacalcidol group ( by 28+/-4 ml/min ) and in the placebo group ( by 26+/-5 ml/min ) ( P<0.05 ) , with no difference being detected between the groups . CONCLUSIONS Long-term treatment with alfacalcidol is safe and might be beneficial for the preservation of bone mass in the pre-dialysis stages of CRF , most likely through a reduction in bone turnover as estimated from the changes of the biochemical bone markers Active vitamin D3 is extensively used for the treatment of secondary hyperparathyroidism in hemodialysis patients . But it is often impossible to administer enough dose to suppress parathyroid hormone ( PTH ) level , because of hypercalcemia and hyperphosphatemia . New modalities with higher specificity for PTH suppression are desirable . We conducted a crossover comparative study of falecalcitriol , an active vitamin D3 analog , and alfacalcidol ( 1alpha[OH]D3 ) . In this study , 25 hemodialysis patients with moderate to severe secondary hyperparathyroidism who had normal serum calcium levels were enrolled . They received daily oral doses of alfacalcidol during an 8-week observation period . Based on serum calcium levels and intact PTH , the subjects were allocated into two groups , and a comparative study was conducted using unmasked crossover design of two drugs x two periods . The dosage of both drugs was adjusted to maintain the initial serum calcium levels , and the relative change ( % change ) of serum biochemical parameters were compared . Comparison of two drugs in period 1 was taken as primary efficacy evaluation . Reproducibility of drug action was confirmed by comparing the effect of falecalcitriol between period 1 and 2 . The percent change of PTH of falecalcitriol was lower than that of alfacalcidol : Those were , respectively , -7.89 % and + 30.42 % for c-terminal PTH ( P = 0.022 ) , -4.39 % and + 38.88 % for i-PTH ( P = 0.077 ) , and + 3.68 % and + 30.52 % for midregion PTH ( P = 0.099 ) . The similar changes were observed in the falecalcitriol group during period 2 , confirming the reproducibility . Falecalcitriol was found to be superior to alfacalcidol in suppression of PTH levels in patients with moderate to severe secondary hyperparathyroidism when it is administered in equivalent doses that might maintain similar serum calcium levels BACKGROUND Elevated calcium and phosphorus levels after therapy with injectable vitamin D for secondary hyperparathyroidism may accelerate vascular disease and hasten death in patients undergoing long-term hemodialysis . Paricalcitol , a new vitamin D analogue , appears to lessen the elevations in serum calcium and phosphorus levels , as compared with calcitriol , the st and ard form of injectable vitamin D. METHODS We conducted a historical cohort study to compare the 36-month survival rate among patients undergoing long-term hemodialysis who started to receive treatment with paricalcitol ( 29,021 patients ) or calcitriol ( 38,378 patients ) between 1999 and 2001 . Crude and adjusted survival rates were calculated and stratified analyses were performed . A subgroup of 16,483 patients who switched regimens was also evaluated . RESULTS The mortality rate among patients receiving paricalcitol was 3417 per 19,031 person-years ( 0.180 per person-year ) , as compared with 6805 per 30,471 person-years ( 0.223 per person-year ) among those receiving calcitriol ( P<0.001 ) . The difference in survival was significant at 12 months and increased with time ( P<0.001 ) . In the adjusted analysis , the mortality rate was 16 percent lower ( 95 percent confidence interval , 10 to 21 percent ) among paricalcitol-treated patients than among calcitriol-treated patients . A significant survival benefit was evident in 28 of 42 strata examined , and in no stratum was calcitriol favored . At 12 months , calcium and phosphorus levels had increased by 6.7 and 11.9 percent , respectively , in the paricalcitol group , as compared with 8.2 and 13.9 percent , respectively , in the calcitriol group ( P<0.001 ) . The two-year survival rate among patients who switched from calcitriol to paricalcitol was 73 percent , as compared with 64 percent among those who switched from paricalcitol to calcitriol ( P=0.04 ) . CONCLUSIONS Patients who receive paricalcitol while undergoing long-term hemodialysis appear to have a significant survival advantage over those who receive calcitriol . A prospect i ve , r and omized study is critical to confirm these findings BACKGROUND Hyperphosphataemia in dialysis patients is associated with significant morbidity . We assessed the ability of lanthanum carbonate to control phosphate levels in patients undergoing haemodialysis or continuous ambulatory peritoneal dialysis ( CAPD ) in a short-term , placebo-controlled study . METHODS This was a double-blind , placebo-controlled , parallel-group study consisting of three phases : a 2 week washout period ; a 4 week , open-label , dose-titration phase ; and a 4 week , double-blind , placebo-controlled phase . After washout , patients ( n = 59 ) received lanthanum ( 375 mg/day ) , titrated up to a maintenance dose ( maximum : 2250 mg ) that achieved control of serum phosphate levels between 1.3 and 1.8 mmol/l ( 4.03 - 5.58 mg/dl ) . After titration , patients were r and omized to receive their maintenance dose of lanthanum ( n = 17 ) or placebo ( n = 19 ) for 4 weeks . Control of serum phosphate was the primary efficacy assessment . Levels of calcium , parathyroid hormone , calcium x phosphate product and lanthanum as well as adverse events were evaluated . RESULTS By the end of titration , 70 % of patients had serum phosphate levels < or = 1.8 mmol/l . Lanthanum carbonate continued to control serum phosphate levels in the double-blind phase . At the end of the study , 64.7 % of lanthanum carbonate-treated patients were controlled compared with 21.4 % in the placebo group . Results in patients receiving CAPD were similar to those seen in the group as a whole . Mean parathyroid hormone levels ( P = 0.41 ) and calcium x phosphate product ( P<0.001 ) were both higher in the placebo than the lanthanum carbonate group . CONCLUSIONS Lanthanum carbonate is an effective phosphate binder able to control serum phosphate and calcium x phosphate product BACKGROUND Cinacalcet lowers plasma parathyroid hormone ( PTH ) levels in primary and secondary hyperparathyroidism . The efficacy and safety of cinacalcet have not been examined in renal transplant patients with persistent hyperparathyroidism . The aim of this study was to evaluate the effect of cinacalcet as a novel therapy for the management of such patients . METHODS Eleven renal allograft recipients with persistent hyperparathyroidism were treated with cinacalcet . The total study time was 10 weeks . Individual cinacalcet doses were adjusted to obtain a serum calcium in the predefined normal target range of 2.10 - 2.60 mmol/l . RESULTS Serum calcium decreased significantly from 2.73+/-0.05 mmol/l to 2.44+/-0.05 and 2.42+/- 0.04 mmol/l after 2 and 10 weeks of treatment , respectively . All patients reached the target range rapidly and remained normocalcaemic throughout the study . Serum PTH significantly decreased 16.1 and 21.8 % at study weeks 2 and 10 , respectively , compared with week 0 . Serum phosphate increased . Renal function remained stable and no allograft rejection was observed . From weeks 2 to 10 , daily cinacalcet doses administered were 30 mg ( n = 8) , 15 mg ( n = 1 ) and 60 mg ( n = 1 ) , respectively . CONCLUSION Cinacalcet was effective in correcting the hypercalcaemia associated with persistent hyperparathyroidism after renal transplantation . It appears to be safe . Thus , cinacalcet represents a promising alternative for parathyroidectomy in these patients Recent studies in adults have suggested that parenteral 1,25-dihydroxyvitamin D3 ( 1,25[OH]2D3 ) may have advantages over oral therapy in the management of renal osteodystrophy . The purpose of this study was to determine whether there were clear differences between oral and IP 1,25(OH)2D3 treatments in children who did not pose a treatment problem . Seven children ( 5 males , 2 females , aged 1.8 to 16 years , median 4.8 years ) undergoing peritoneal dialysis were initially treated with oral 1,25(OH)2D3 for a one month equilibration period They were r and omly assigned to 3 months of either oral or intraperitoneal ( IP ) therapy with 1,25(OH)2D3 followed by 3-months-treatment using the alternative route . No significant differences in serum creatinine , phosphate , or parathyroid hormone concentrations were found between the different routes of administration in the patients . No significant differences in height st and ard deviation scores or renal osteodystrophy scores were found over the six-month study . Paired oral and IP pharmacokinetic studies were performed on these 7 patients and 2 other children who had been treated for at least 2 months using either oral or IP 1,25(OH)2D3 . Serum was taken prior to one of the usual 1,25(OH)2D3 doses and 0.5 , 1.5 , 3 , 6 , and 24 h afterward . The highest measured concentrations of 1,25(OH)2D3 were found at 1.5 h for both oral and IP treatments ( mean Cmax [ SD ] : oral 116 [ 23 ] pmol/l , IP 121 [ 24 ] pmol/l , p > 0.05 ) . The AUC 's for oral and IP therapy were similar ( 1701 [ 276 ] and 1645 [ 301 ] pmol/h/l , respectively ) . In the paired pharmacokinetic studies no significant differences were found between oral and IP treatments for the serum half life ( 27.4 [ 11.6 ] h and 19.2 [ 8.1 ] h , respectively ) and total body clearance ( 15.3 [ 2.1 ] h and 18.4 [ 3.3 ] h , respectively ) of 1,25(OH)2D3 . In children who respond appropriately to oral 1,25(OH)2D3 there is no biological advantage to the use of IP 1,25(OH)2D3 Abstract Objective : To determine whether alfacalcidol — used in management of overt renal bone disease — may safely prevent renal bone disease when used earlier in course of renal failure . Design : Double blind , prospect i ve , r and omised , placebo controlled study . Setting : 17 nephrology centres from Belgium , France , the Netherl and s , and the United Kingdom . Subjects : 176 patients aged 18–81 with mild to moderate chronic renal failure ( creatinine clearance 15–50 ml/min ) and with no clinical , biochemical , or radiographic evidence of bone disease . Interventions : Alfacalcidol 0.25 μg ( titrated according to serum calcium concentration ) or placebo given for two years . Main outcome measures : Quantitative histology of bone to assess efficacy of treatment and renal function to assess safety . Results : 132 patients had histological evidence of bone disease at start of study . Biochemical , radiographic , and histological indices of bone metabolism were similar for the 89 patients given alfacalcidol and the 87 controls given placebo . After treatment , mean serum alkaline phosphatase activity and intact parathyroid hormone concentration had increased by 13 % and 126 % respectively in controls but had not changed in patients given alfacalcidol ( P<0.001 ) . Hypercalcaemic episodes occurred in 10 patients given alfacalcidol ( but responded to decreases in drug dose ) and in three controls . Histological indices of bone turnover significantly improved in patients given alfacalcidol and significantly deteriorated in controls : among patients with abnormal bone histology before treatment , bone disease resolved in 23 ( 42 % ) of those given alfacalcidol compared with two ( 4 % ) of the controls ( P<0.001 ) . There was no difference in rate of progression of renal failure between the two groups . Conclusion : Early administration of alfacalcidol can safely and beneficially alter the natural course of renal bone disease in patients with mild to moderate renal failure . Key messages Key messages Treating such patients with alfacalcidol ( up to 1 μg/day for two years ) significantly improved their osteomalacia and hyperparathyroid disease Treatment had no apparent adverse effect on renal function Hypercalcaemic episodes were uncommon and readily responded to decreases in drug dose Alfacalcidol might be used more widely for patients with moderate renal failure not yet needing Fifty-seven patients who had been receiving maintenance haemodialysis for a mean of 4.6 years were given 0.25 - 0.5 microgram oral 1,25-dihydroxy ( 1,25-(OH)2 ) vitamin D3 or a placebo in a double-blind manner for one to two years . In patients with normal radiographs ( mean plasma parathyroid hormone concentration 205 microliterEq/ml ) 1,25-(OH)2 vitamin D3 prevented the development of the radiological appearances of hyperparathyroidism . In patients with abnormal radiographs ( mean plasma parathyroid concentration 709 microliterEq/ml ) 1,25-(OH)2 vitamin D3 arrested or reversed the radiological changes of hyperparathyroidism . Nevertheless , the response was slow and the concentration of the hormone remained considerably raised ( mean 445 microliterEq/ml ) . It is concluded from these results that giving 1,25-(OH)2 vitamin D3 to patients receiving maintenance haemodialysis who have normal h and radiographs or minimal erosions is beneficial . In patients with more advanced hyperparathyroidism parathyroidectomy should be considered unless there is a rapid response This study compared the effects of oral and intravenous calcitriol on serum biochemistry parameters and levels of bone-resorptive cytokines in haemodialysis patients . Patients were r and omized to receive oral ( n = 18 ) or intravenous ( n = 16 ) calcitriol treatment for 6 months . Serum levels of total calcium , ionized calcium , intact parathyroid hormone ( iPTH ) , magnesium , alkaline phosphatase , tumour necrosis factor-α ( TNF-α ) , interleukin (IL)-1 and IL-6 were measured at baseline and after 3 and 6 months of treatment . After treatment , serum levels of iPTH , total calcium , ionized calcium , TNF-α , IL-1 and IL-6 were not significantly different from baseline . The intravenous calcitriol treatment group showed significant decreases in levels of iPTH , TNF-α , IL-1 and IL-6 and a significant increase in total calcium level after 3 and 6 months . There was no significant change in serum ionized calcium levels . Significantly decreased serum alkaline phosphatase and magnesium levels were found in both treatment groups after 3 and 6 months . In conclusion , intravenous calcitriol treatment has a significant depressive effect on iPTH and bone-resorptive cytokines in patients undergoing haemodialysis BACKGROUND Management of secondary hyperparathyroidism has included the use of active vitamin D or vitamin D analogs for the suppression of parathyroid hormone ( PTH ) secretion . Although , these agents are effective , therapy is frequently limited by hypercalcemia , hyperphosphatemia , and /or elevations in the calcium-phosphorus ( Ca x P ) product . In clinical studies , paricalcitol was shown to be effective at reducing PTH concentrations without causing significant hypercalcemia or hyperphosphatemia as compared to placebo . A comparative study was undertaken in order to determine whether paricalcitol provides a therapeutic advantage to calcitriol . METHODS A double-blind , r and omized , multicenter study comparing the safety and effectiveness of intravenous paricalcitol and calcitriol in suppressing PTH concentrations in hemodialysis patients was performed . A total of 263 r and omized patients were enrolled at domestic and international sites . Following the baseline period , patients with serum Ca x P < 75 , and a PTH level > or = 300 pg/mL were r and omly assigned to receive either paricalcitol or calcitriol in a dose-escalating fashion for up to 32 weeks . Dose adjustments were based on laboratory results for PTH , calcium , and Ca x P. The primary end point was the greater than 50 % reduction in baseline PTH . Secondary end points were the occurrence of hypercalcemia and elevated Ca x P product . RESULTS Paricalcitol-treated patients achieved a > or = 50 % reduction from baseline PTH significantly faster than did the calcitriol-treated patients ( P = 0.025 ) and achieved a mean reduction of PTH into a desired therapeutic range ( 100 to 300 pg/mL ) at approximately week 18 , whereas the calcitriol-treated patients , as a group , were unable to achieve this range . Moreover , paricalcitol-treated patients had significantly fewer sustained episodes of hypercalcemia and /or increased Ca x P product than calcitriol patients ( P = 0.008 ) . CONCLUSION Paricalcitol treatment reduced PTH concentrations more rapidly with fewer sustained episodes of hypercalcemia and increased Ca x P product than calcitriol therapy The efficacy of 1 alpha-hydroxycholecalciferol in the prevention of renal osteodystrophy in children commencing continuous ambulatory peritoneal dialysis was studied in 12 patients , 0.8 - 17 years of age , who were r and omly assigned to either group I receiving st and ard therapy or to group II receiving in addition 10 - 20 ng/kg body weight/day of 1 alpha-hydroxycholecalciferol . Calcium carbonate compounds were used to control hyperphosphataemia . Mean plasma calcium ( total and ionised ) and phosphate levels were not significantly different between the two groups . All group I patients continued to have elevated plasma immunoreactive parathyroid hormone levels at 6 months compared to only 1 patient in group II ( p less than 0.05 ) . Four patients in group I developed subperiosteal erosions on radiography compared to the healing of mild lesions in 2 patients in group II . Bone histomorphometry on iliac crest needle biopsy specimens revealed a significant reduction in osteoid index and seam width in group II . Serum aluminum levels decreased during the course of continuous ambulatory peritoneal dialysis , and the significant staining for bone aluminum in 6 patients at the beginning of the study was no longer present in 5 patients at 6 months . Our data demonstrate that 1 alpha-hydroxycholecalciferol is beneficial in the prevention and treatment of bone disease in children on continuous ambulatory peritoneal dialysis Secondary hyperparathyroidism is a common feature of chronic renal failure and vitamin D deficiency plays an important role in the development of this abnormality . Several therapeutical calcitriol schedules have been used in treating uremic hyperparathyroidism but recently oral boluses have been proposed as more effective . In this study we compare the efficacy of three different oral calcitriol regimens in suppressing iPTH secretion in predialytic chronic renal failure . Sixteen ( 16 ) patients ( mean age 51 + /- 16 years ; creatinine clearance 22.9 + /- 9.8 ml ; range 8 - 32 ml/min ) were treated in a cross-over r and omized design with oral daily calcitriol 0.5 micrograms/die ( Treatment A ) , three oral boluses of 2 micrograms of calcitriol a week ( Treatment B ) and a single oral bolus of 2 micrograms of calcitriol a week ( Treatment C ) . All treatment periods lasted three months and were followed by a wash-out period of one month . Serum iPTH ( Allegro Nichols ) , 1 - 25 vitamin D ( IRMA-MAB ) , total and ionized calcium ( Nova 8 Pabish ) , serum phosphate , alkaline phosphatase and creatinine clearance were measured every two weeks . Serum iPTH was also determined in a control group of fifteen ( 15 ) patients ( mean age 47 + /- 12 years , creatinine clearances of 21 + /-12 ml/min ) observed for three months without calcitriol treatment . Daily oral intake of 0.5 micrograms of calcitriol prevents an increase of iPTH without causing hypercalcemia , but only oral boluses ( B and C ) decreased iPTH : from 270 + /- 169 pg/ml to 135 + /- 76 pg/ml ( p < 0.01 ; B ) and to 165 + /- 121 pg/ml ( p < 0.05 ; C ) . Serum iPTH increased from 293 + /- 121 to 323 + /- 129 pg/ml ( p = n.s . ) . No significant differences in renal function were observed during the different study periods . Our results confirm the good efficacy of multiple calcitriol oral boluses but also suggest for the first time a single weekly bolus as a reliable approach to the treatment of secondary hyperparathyroidism in pre-dialytic renal failure Introduction : Increased serum levels of bone-resorptive cytokines such as interleukin-1β ( IL-1β ) and interleukin-6 ( IL-6 ) have been implicated for changes in bone remodeling in hemodialysis patients . In this prospect i ve r and omized study , we aim ed to compare the effect of oral and intravenous ( IV ) pulse calcitriol on serum levels of IL-1β and IL-6 . Patients and Methods : Twenty-eight hemodialysis patients were included and consecutively r and omized to receive either oral ( n = 14 , M/F = 7/7 , mean age 42 ± 15 years ) or IV pulse ( n = 14 , M/F = 6/8 , mean age 38 ± 14 years ) calcitriol treatment . No difference was found between groups for age , sex distribution , primary renal disease , mean time on hemodialysis and baseline biochemical parameters including serum levels of IL-1β and IL-6 . Results : The percent fall of intact parathyroid hormone ( iPTH ) was significantly less with oral compared to IV calcitriol between 0 and the 3rd month ( 32 ± 21 vs. 56 ± 28 % , p = 0.03 ) . However , the percent fall in iPTH at the 6th month of the therapy was not different in the oral group compared to the IV group ( 57 ± 22 vs. 73 ± 24 % , p = 0.12 ) . The increase in bone mineral densities was higher in the IV group than the oral group . Oral and IV calcitriol caused a significant fall in IL-1β ( p = 0.02 and p = 0.03 , respectively ) and IL-6 levels ( p = 0.02 and p < 0.001 , respectively ) at the 6th month of treatment . The percent fall in serum IL-6 levels at the 6th month was significantly greater in the IV compared to the oral group ( 61 ± 18 vs. 36 ± 33 % , p = 0.04 ) , while the percent changes in serum IL-1β levels were similar . Conclusion : IV calcitriol therapy has a greater suppression of PTH at the 3rd month of the therapy . Despite no difference in serum PTH levels at the 6th month , IV therapy has a greater increase in bone mineral densities and a greater decrease in serum IL-6 levels . These findings suggest IV calcitriol treatment has a superior effect on bone remodeling by influencing the levels of bone-resorptive cytokines as compared to the oral therapy group , beyond its suppressive effect on iPTH BACKGROUND Cardiovascular disease is frequent and severe in patients with end-stage renal disease . Disorders of mineral metabolism may contribute by promoting cardiovascular calcification . METHODS We conducted a r and omized clinical trial comparing sevelamer , a non-absorbed polymer , with calcium-based phosphate binders in 200 hemodialysis patients . Study outcomes included the targeted concentrations of serum phosphorus , calcium , and intact parathyroid hormone ( PTH ) , and calcification of the coronary arteries and thoracic aorta using a calcification score derived from electron beam tomography . RESULTS Sevelamer and calcium provided equivalent control of serum phosphorus ( end-of- study values 5.1 + /- 1.2 and 5.1 + /- 1.4 mg/dL , respectively , P = 0.33 ) . Serum calcium concentration was significantly higher in the calcium-treated group ( P = 0.002 ) , and hypercalcemia was more common ( 16 % vs. 5 % with sevelamer , P = 0.04 ) . More subjects in the calcium group had end-of- study intact PTH below the target of 150 to 300 pg/mL ( 57 % vs. 30 % , P = 0.001 ) . At study completion , the median absolute calcium score in the coronary arteries and aorta increased significantly in the calcium treated subjects but not in the sevelamer-treated subjects ( coronary arteries 36.6 vs. 0 , P = 0.03 and aorta 75.1 vs. 0 , P = 0.01 , respectively ) . The median percent change in coronary artery ( 25 % vs. 6 % , P = 0.02 ) and aortic ( 28 % vs. 5 % , P = 0.02 ) calcium score also was significantly greater with calcium than with sevelamer . CONCLUSIONS Compared with calcium-based phosphate binders , sevelamer is less likely to cause hypercalcemia , low levels of PTH , and progressive coronary and aortic calcification in hemodialysis patients Intermittent bolus administration of calcitriol -- i.e . , 1,25-dihydroxycholecalciferol or 1,25-(OH)2D3 - -is highly efficacious in dialysis patients . In experimental studies , intermittent administration of calcitriol is superior to continuous administration in suppressing preproparathyroid hormone ( PTH ) mRNA and circulating PTH concentrations . In a r and omized , prospect i ve , open multicenter trial 45 dialysis patients with elevated 1,84-iPTH ( > or = 20 pmol/l , normal 1 - 6 pmol/l ) levels were r and omly allocated to daily administration of 0.75 microgram calcitriol ( continuous ) or twice weekly administration ( intermittent ) ; the two protocol s provided an identical total weekly doses of 5.25 micrograms calcitriol . Patients were dialyzed with a dialysate Ca concentration of 1.75 mmol/l and had oral CaCO3 or Ca acetate . 1,84-iPTH ( immunoradiometric assay ) and serum Ca and Pi levels were measured weekly . At the beginning of the study , the median 1,84-iPTH value was 37 pmol/l ( range 20 - 115 ) in the intermittent versus 36 pmol/l ( range 21 - 72 ) in the continuous calcitriol group . After 2 weeks , the median 1,84-iPTH level was 18.5 pmol/l ( range 1.4 - 106 ) versus 18 pmol/l ( range 1.2 - 48 ) . After 12 weeks , 11 of 21 of the patients in the intermittent and 18 of 24 patients in the continuous group had reached the treatment goal , i.e. , 1,84-iPTH < or = 10 pmol/l without hypercalcemia or hyperphosphatemia . There were seven episodes of hypercalcemia ( > 2.7 mmol/l ) in the intermittent versus two in the continuous group ; the mean peak Ca level was 2.8 mmol/l ( range 2.76 - 3.0 ) versus 2.9 mmol/l ( range 2.74 - 3.06 ) . There were 21 versus 17 episodes , respectively , of hyperphosphatemia ( > 2.2 mmol/l ) Paricalcitol ( 19-nor-1alpha-25-dihydroxyvitamin D2 ) , a new vitamin D analog developed for the treatment of secondary hyperparathyroidism , was evaluated in three double-blind , placebo-controlled , dose-escalating , r and omized multicenter trials . A total of 78 patients ( 40 Paricalcitol injection , 38 placebo ) achieved treatment phase eligibility , which included intact parathyroid hormone ( iPTH ) > or = 400 pg/ml , normalized serum calcium levels between 8.0 and 10.0 mg/dl , and calcium x phosphorus product values less than 75 . Study end points included a decrease in iPTH of at least 30 % or a maximum of five dose escalations . After a 4-wk washout , paricalcitol or placebo was administered intravenously three times per week after dialysis for 12 wk . Study drug was started at a dose of 0.04 microg/kg and was increased by 0.04 microg/kg every 2 wk to a maximal allowable dose of 0.24 microg/kg or until at least a 30 % decrease in serum iPTH was achieved . The dose of paricalcitol that decreased iPTH by at least 30 % became the maintenance dose . Of 40 patients receiving paricalcitol , 27 ( 68 % ) had at least a 30 % decrease in serum iPTH for 4 consecutive weeks , compared with three of 38 patients ( 8 % ) receiving placebo ( P < 0.001 ) . For patients who received 12 wk of treatment with paricalcitol , the levels of iPTH decreased significantly from 795+/-86 to 406+/-106 pg/ml ( P < 0.001 ) , whereas the values for PTH were 679+/-41 pg/ml before and 592+/-41 pg/ml after 12 wk of therapy in patients receiving placebo ( P = NS ) . Also , there was a significant difference between treatment groups for the change from baseline PTH levels ( P < 0.001 ) . Paricalcitol treatment result ed in a significant reduction in serum alkaline phosphatase from 148+/-23 U/L to 101+/-14 U/L ( P < 0.001 ) in patients treated for 12 wk compared with 120+/-9 U/L to 130+/-11 U/L ( P = NS ) in patients receiving placebo for 12 wk . Importantly , hypercalcemia did not occur before achieving target serum iPTH levels in any of the paricalcitol-treated patients . There was no significant difference for the change from baseline in serum phosphorus within or between treatment groups . There was no significant difference in adverse events between the paricalcitol and placebo-treated groups . These studies demonstrate that paricalcitol safely and effectively suppresses iPTH levels in hemodialysis patients . This second generation vitamin D analog may have a wider therapeutic window than current vitamin D preparations , and thus may allow reduction in PTH with less hypercalcemia Because intravenous ( iv ) calcitriol has greater bioavailability than oral calcitriol , it may be more efficacious in suppressing parathyroid hormone ( PTH ) secretion . In this study , the pharmacokinetics and efficacy of pulse oral and i.v . calcitriol were compared . Patients were r and omized to receive 2 micrograms of i.v . or oral calcitriol after each dialysis . Two pharmacokinetic studies ( PK1 , PK2 ) were performed 10 days apart , during which the patients received calcitriol after each dialysis . Calcitriol bioavailability was determined from the area under the curve ( AUCtime interval ( hours ) in pg/mL per h ) . After the PK phase , PTH was lowered to < 200 pg/mL by titrating calcitriol to a maximum of 12 micrograms/wk over 4 wk . Calcitriol was then maintained for another 18 wk unless serum calcium exceeded 11.5 mg/dL or Ca x P product exceeded 70 ; when these limits were reached , calcitriol was held and then restarted at a lower dose . After i.v . administration , peak serum calcitriol exceeded that achieved orally but by 1 h , calcitriol levels were similar . The AUC0 - 0.5 ( 105 + /- 12 , i.v . ; 9 + /- 4 , oral ) and AUC0.5 - 1 ( 68 + /- 6 , i.v . ; 30 + /- 7 , oral ) were higher with i.v . ( P < 0.05 ) , but cumulative AUC0 - 48 did not differ . Individual t1/2 values ranged from 10 to 129 h for PK1 and from 10 to 50 h for PK2 . The t1/2 for oral calcitriol was 38 + /- 14 h for PK1 and 30 + /- 4 h for PK2 ( not significant ( NS ) ) . The t1/2 for i.v . calcitriol was 26 + /- 5 h for PK1 and 19 + /- 3 h for PK2 ( NS , PK1 versus PK2 and oral versus i.v . ) . When the PK1 oral and i.v . data were combined , the mean t1/2 was 32 + /- 7 h whereas the t1/2 for PK2 ( oral and i.v . ) was 22 + /- 3 h ( P < 0.05 ) . Baseline PTH levels were 510 + /- 90 pg/mL and 499 + /- 79 pg/mL , oral and i.v . , respectively . Serum PTH level at 22 wk was not different between oral and i.v . groups , 153 + /- 38 pg/mL and 214 + /- 124 pg/mL in i.v . ( NS ) . The percentage of PTH suppression was 66 + /- 7.4 % in the oral group and 69 + /- 12 % in the i.v . group ( NS ) . A major degree of serum iPTH suppression occurred during the initial 4 wk of treatment , concomitant with a rise in serum calcium levels . Adverse effects were similar between groups , as were the average dosages of calcitriol and phosphate binders . In conclusion , the efficacy of intravenous and pulse oral calcitriol were similar in hemodialysis patients with secondary hyperparathyroidism . The early rise in serum calcium levels observed with treatment may have contributed significantly to the suppression of serum iPTH levels . The difference in bio-availability between the different routes does not have a clinical ly apparent effect . The t1/2 varied widely among individuals , whereas exposure to calcitriol may decrease the t1/2 The dose-response relationships and the safety of administering 22-oxacalcitriol ( OCT ) to patients with secondary hyperparathyroidism ( 2HPT ) under regular three-times-weekly hemodialysis ( HD ) were evaluated by double-blind parallel group design . A total of 203 patients with 2HPT were r and omly allocated into four groups , and 5 microg ( Group L ) , 10 microg ( Group M ) , or 15 microg ( Group H ) OCT , or placebo ( Group P ) was administrated at the end of every HD for 12 weeks . Reductions of intact-parathyroid hormone ( iPTH ) concentration greater than 30 % from baseline were observed in 7.7 % of Group P as compared to 77.3 % of the pooled OCT groups after 12 weeks of treatment ( Mantel test : P < 0.001 ) . Time-trends ( slopes ) of log-iPTH concentration calculated by least-squares line fitting to each patient 's data during treatment differed between Group P and the pooled OCT groups ( t-test : P < 0.001 ) and these iPTH slopes decreased dose-dependently ( linear trend by t-test : P < 0.001 ) . Slopes of serum calcium corrected for albumin ( corrected-sCa ) concentrations also differed between Group P and the pooled OCT groups ( t-test : P < 0.001 ) , and increased dose-dependently ( linear trend by t-test : P < 0.0001 ) . Serum phosphorus and Ca x P product increased significantly only in high dose groups . Slopes of log(iPTH ) and corrected-sCa concentrations were reciprocally related . Most adverse events were hypercalcemia and dose-related , but occasionally comprised pruritus or increased serum creatinine phosphokinase . These results indicate that OCT produced a strong and dose-dependent suppression of PTH and an increase of corrected-sCa concentration in patients with 2HPT . The recommended initial dosages of OCT would appear to be 5 microg when pretreatment iPTH concentrations are less than 500 pg/mL , and 10 microg when greater than 500 pg/mL for safe and effective treatment . As in the case of PTH , calcium and phosphorus showed dose-dependent increases . It is therefore essential to take pre caution s as to possible increases in calcium and phosphorus Both intermittent intravenous and intermittent oral calcitriol have been shown to be effective in the treatment of secondary hyperparathyroidism in hemodialysis patients and it has been cl aim ed that intravenous calcitriol causes less hypercalcemia . However , there has been no published systematic comparison of the two routes of administration of intermittent calcitriol . Therefore in a prospect i ve crossover study 11 ( 9 male ) patients on maintenance hemodialysis were r and omized to receive intravenous followed by oral calcitriol for 4 months each , or oral followed by intravenous calcitriol , commencing at 2 micrograms postdialysis three times per week . Initial serum immunoreactive parathyroid hormone ( PTH ) was 446 + /- 111 ( normal < 65 ) pg/ml . Calcium-containing phosphate binders were not used . Calcitriol was ceased if hypercalcemia developed and restarted at 2 micrograms or 1 microgram when calcium returned to normal . Hypercalcemia was frequent ( 11 episodes in 8 patients on intravenous calcitriol and 10 episodes in 7 patients on oral calcitriol ) and dose reduction to 1 microgram was necessary in 7 patients on intravenous and on 6 patients on oral . Serum PTH fell during both treatments . Parathyroid enlargement was seen in 10 gl and s from 4 patients , but no size reduction was demonstrated with treatment . There was no reduction in activity on quantitative metabolic bone scan . In summary , intermittent oral calcitriol and intermittent intravenous calcitriol were equally effective in reducing serum parathyroid hormone levels and at a dose of 2 micrograms postdialysis caused hypercalcemia with equal frequency A controlled study of the effects of the potent vitamin-D metabolite , 1 , 25-dihydroxycholecalciferol ( 1,25[OH]2D3 ) , and vitamin D3 was done in 18 non-dialysed patients with chronic renal failure ( C.R.F. ) . Patients with a creatinine clearance below 35 ml/min and mild renal osteodystrophy were selected . After 6 months ' observation of the spontaneous course the patients were r and omly allocated to 6 months ' oral treatment with either 1 , 25 (OH)2D3 or vitamin D3 in initial daily doses of 1microgram and 4000 I.U. , respectively , combined with 0.5 g calcium . 1,25(OH)2D3 quickly corrected hypocalcaemia , reduced serum-alkaline-phosphatases and serum-immunoreactive-parathyroid-hormone , and more than doubled the urinary excretion rate of calcium . D3 had similar , but less pronounced effects . 7 out of 8 patients on 1,25(OH)2D3 , developed hypercalcaemia which necessitated a reduction in dosage . None of the patients on D3 treatment developed hypercalcaemia . The percentage fall in creatinine clearance was greater during treatment than before treatment in all patients on 1 , 25 (OH)2D3 ( P less than 0.01 ) and in 7 of 9 patients on vitamin D3 treatment ( though the group change here was not significant ) . Deterioration of renal function is a major limitation of the clinical use of 1 , 25(OH)2D3 and D3 in non-dialysed patients with C.R.F. In fact , the decrased formation of 1 , 25(OH)2D3 seen in C.R.F. might protect renal function at the expense of abnormalities in mineral metabolism UNLABELLED Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients . BACKGROUND In the management of patients with mild secondary hyperparathyroidism , it is not known whether calcium supplementation alone is sufficient to correct abnormalities in bone and mineral metabolism or if calcitriol is needed in either physiologic oral or intravenous pharmacologic doses . METHODS This was a 40-week prospect i ve nonmasked trial of 52 patients [ parathyroid hormone ( PTH ) 150 to 600 pg/mL ] who were r and omized to receive escalating doses of either calcium carbonate ( CaCO3 ) alone ( calcium group , N = 11 ) , daily oral calcitriol ( oral group , N = 20 ) , or intermittent intravenous calcitriol ( IV group , N = 21 ) . The groups were compared with regard to changes in serum intact PTH , serum bone-specific alkaline phosphatase ( BAP ) , incidence of hypercalcemia ( > 10.5 mg/dL ) , and hyperphosphatemia ( > 6.5 mg/dL ) . RESULTS PTH levels decreased in all groups ( P < 0.01 , paired t-test ) . In the calcium group , PTH ( mean + /- SEM ) decreased from 325 + /- 46.2 to 160 + /- 44.5 pg/mL. In the oral group , it decreased from 265 + /- 26.4 to 125 + /- 23.7 pg/mL , and in the IV group , it decreased from 240 + /- 27.7 to 65 + /- 10.0 pg/mL. Upon analysis of covariance , controlling for the initial PTH level , we found no differences in the PTH response between the groups ( P > 0.10 ) . In contrast , the BAP concentration increased from 20.7 + /- 7.6 to 27.5 + /- 7.0 microg/L in the calcium group ( P = 0.17 ) , decreased from 20 . 6 + /- 3.9 to 17.8 + /- 4.5 microg/L in the oral group ( P = 0.26 ) , and from 19.1 + /- 2.6 to 10.6 + /- 1.1 microg/L in the IV group ( P = 0 . 007 ) . Serum calcium increased significantly in all groups from 8.4 + /- 0.25 to 9.0 + /- 0.28 , 8.5 + /- 0.16 to 9.2 + /- 0.27 , and 8.7 + /- 0.16 to 9.4 + /- 0.18 mg/dL in the calcium , oral , and IV groups , respectively ( P = NS difference between groups ) . Serum phosphorus was significantly lower in the calcium group throughout the study ( P = 0.02 ) . Hypercalcemic episodes were 2.0 + /- 0.8 , 3.0 + /- 0.6 , and 3 . 4 + /- 0.6 per patient-year ( P > 0.10 ) , and hyperphosphatemic episodes were 0.9 + /- 0.56 , 4.2 + /- 0.79 and 4.9 + /- 0.84 in the calcium , oral , and IV groups , respectively ( P < 0.01 ) . CONCLUSION In mild secondary hyperparathyroidism , all three strategies are effective . High-dose CaCO3 alone may be sufficient to control PTH with a favorable side-effect profile , but calcitriol appears to have additional suppressive effects on bone that are greater following the intravenous route of administration and may increase the risk of adynamic bone disease Current treatment of secondary hyperparathyroidism in chronic kidney failure with calcium and active vitamin D is potentially limited by hypercalcemia and hyperphosphatemia . AMG 073 represents a new class of compounds for the treatment of hyperparathyroidism known as calcimimetics , which reduce parathyroid hormone ( PTH ) synthesis and secretion by increasing the sensitivity of the parathyroid calcium-sensing receptor ( CaR ) to extracellular calcium . The current study evaluates the efficacy and safety of AMG 073 when added to conventional treatment of secondary hyperparathyroidism in end-stage renal disease ( ESRD ) . Seventy-one hemodialysis patients with uncontrolled secondary hyperparathyroidism , despite st and ard therapy with calcium , phosphate binders , and active vitamin D sterols , were treated in this 18-wk , dose-titration study with single daily oral doses of AMG 073/placebo up to 100 mg . Changes in plasma PTH , serum calcium , serum phosphorus , and calcium x phosphorus levels were compared between AMG 073 and placebo groups . Mean PTH decreased by 33 % in the AMG 073 patients compared with an increase of 3 % in placebo patients ( P = 0.001 ) . A significantly greater proportion of AMG 073 patients ( 44 % ) had a mean PTH < or = 250 pg/ml compared with placebo patients ( 20 % ; P = 0.029 ) . Also , a significantly greater proportion of AMG 073 patients ( 53 % ) had a decrease in PTH > or = 30 % compared with placebo patients ( 23 % ; P = 0.009 ) . Calcium x phosphorus levels decreased by 7.9 % in AMG 073 patients compared with an increase of 11.3 % in placebo patients ( P = 0.013 ) . Adverse event rates were low and mostly mild to moderate in severity ; however , the incidence of vomiting was higher in AMG 073 patients . In this study , the calcimimetic AMG 073 at doses up to 100 mg for 18 wk provided a safe and effective means to attain significant reductions in PTH and calcium x phosphorus levels in ESRD patients . AMG 073 represents a novel and promising therapy to improve the management of secondary hyperparathyroidism BACKGROUND Secondary hyperparathyroidism develops early in patients with chronic kidney disease ( CKD ) . Clinical guidelines from the National Kidney Foundation-Kidney/Disease Outcomes Quality Initiative emphasize the need to control parathyroid hormone ( PTH ) , calcium , and phosphorus levels in patients with CKD not receiving dialysis to reduce poor outcomes . This phase 2 study evaluated the effects of the oral calcimimetic cinacalcet hydrochloride in patients with CKD not on dialysis therapy . METHODS A r and omized , double-blind , placebo-controlled , 18-week study enrolled adults with an estimated glomerular filtration rate of 15 to 50 mL/min/1.73 m2 ( 0.25 to 0.83 mL/s/1.73 m2 ) and an intact PTH ( iPTH ) level greater than 130 pg/mL ( ng/L ) . Cinacalcet ( or placebo ) was titrated from 30 to 180 mg once daily to obtain a 30 % or greater reduction in iPTH levels from baseline . RESULTS Baseline mean iPTH levels were 243 pg/mL ( ng/L ) in the cinacalcet group ( n = 27 ) and 236 pg/mL ( ng/L ) in the control group ( n = 27 ) . At baseline , 28 % of subjects were being administered vitamin D sterols and 43 % were being administered phosphate binders or calcium supplements . The addition of cinacalcet significantly decreased iPTH concentrations compared with controls during the efficacy- assessment phase : 56 % versus 19 % of subjects achieved a 30 % or greater reduction in iPTH levels ( P = 0.006 ) , and mean iPTH levels decreased by 32 % in the cinacalcet group , but increased by 6 % in the control group ( P < 0.001 ) . Mean serum calcium and phosphorus levels remained within normal range throughout the study . Cinacalcet generally was well tolerated ; the most frequent adverse events were gastrointestinal . CONCLUSION This preliminary study provides evidence that cinacalcet is efficacious for the treatment of secondary hyperparathyroidism in subjects with CKD not receiving dialysis Abstract Calcitriol oral pulse therapy has been suggested as the treatment of choice for secondary hyperparathyroidism , but its efficacy and safety are still under discussion . The present r and omized multicenter study compares the effect of an 8-week course of daily versus intermittent ( twice weekly ) calcitriol therapy on parathyroid hormone ( PTH ) suppression in 59 children ( mean age 8.4±4.7 years ) with chronic renal insufficiency ( mean Ccr 22.4±11.6 ml/min per 1.73 m2 ) and secondary hyperparathyroidism . After a 3-week washout period , the patients were r and omly assigned to treatment with daily oral calcitriol ( 10 ng/kg per day ) or intermittent oral calcitriol ( 35 ng/kg given twice a week ) . The calcitriol dose was not changed throughout the study period of 8 weeks . At start of the study , the median intact PTH ( iPTH ) level was 485 pg/ml ( range 83–2032 ) in the daily group ( n=29 ) and 315 pg/ml ( range 93–1638 ) in the intermittent group ( n=30 ) . After 8 weeks , the respective median iPTH concentrations were 232 pg/ml ( range 63–1614 ) and 218 pg/ml ( range 2–1785 ) ( ns ) . The mean iPTH decrease from baseline was 19.2±57.8 % and 13.7±46.7 % respectively ( not significant ) . Calcitriol reduced the iPTH concentration in 23/29 patients in the daily group and in 21/30 in the intermittent group . One episode of hypercalcemia ( > 11.5 mg/dl ) was observed in both groups and a single episode of hyperphosphatemia ( > 7.5 mg/dl ) was observed in the daily group . It is concluded that oral calcitriol pulse therapy does not control secondary hyperparathyroidism more effectively than the daily administration of calcitriol in children with chronic renal failure prior to dialysis To examine the most effective route ( intravenous vs. " pulse " oral ) , dose ( physiologic vs. pharmacologic ) and long-term efficacy of calcitriol therapy for secondary hyperparathyroidism in patients with end-stage renal disease ( ESRD ) , we r and omized 19 hemodialysis patients with severe hyperparathyroidism to receive over a 36-week study period either pulse orally administered calcitriol and intravenous placebo ( pulse oral group ; N = 9 ) or intravenous calcitriol and oral placebo ( intravenous group ; N = 10 ) . Calcitriol was given intermittently in a double-blinded fashion at an initial dose of 2 micrograms thrice weekly and increased as tolerated up to a maximum dose of 4 micrograms per treatment . All patients received similar daily calcium supplementation ( 2.5 g of elemental calcium ) and low dialysate calcium ( 1.25 mmol/liter ) throughout the study period . At the maximum tolerated calcitriol dose , serum 1,25-dihydroxyvitamin D levels were significantly greater 60 minutes following intravenous ( 389 pmol/liter ) compared to oral administration ( 128 pmol/liter ) . In spite of the different pharmacologic profiles , intravenous and oral administered calcitriol result ed in similar reductions of serum PTH over the 36 week period of observation ( P = 0.300 ) , achieving an overall maximum average PTH reduction of 43 % ( P = 0.016 ) . Long-term intensive calcitriol therapy ( independent of administration route ) , however , failed to decrease parathyroid gl and size as assessed by high resolution ultrasound and /or magnetic resonance imaging . Calcitriol therapy also failed to alter the calcium sensitivity as assessed by serial PTH measurements in response to calcium loading . Increases in serum calcium , but not calcitriol dose or parathyroid gl and size , predicted decrements in serum PTH , whereas hyperphosphatemia and the level of PTH suppression derived from the PTH/ionized calcium response curves predicted refractoriness to calcitriol therapy . Episodes of hypercalcemia and hyperphosphatemia were similar in both treatment groups and limited the dose of calcitriol that could be administered . These data indicate that intermittent intensive calcitriol therapy , regardless of administration route , is poorly tolerated , fails to correct parathyroid gl and size and functional abnormalities , and has a limited ability to achieve sustained serum PTH reductions in end-stage renal failure patients with severe hyperparathyroidism In this double-blind , placebo-controlled , r and omized , multicenter study , 35 patients with end-stage renal disease undergoing maintenance hemodialysis were treated three times weekly for 4 weeks with either 19-nor-1,25-dihydroxyvitamin D2 ( paricalcitol ) intravenously at doses ranging from 0.04 to 0.24 microg/kg or placebo . Eligible patients with secondary hyperparathyroidism ( HPT ; intact parathyroid hormone [ iPTH ] level > 300 pg/mL ) were initially withdrawn from any existing vitamin D therapy over a 4-week washout period and then r and omized to treatment for 4 weeks with either paricalcitol or placebo . Overall , there was a clinical ly and statistically significant reduction in iPTH level for patients receiving paricalcitol compared with placebo ( P = 0.006 ) . The study end point for efficacy was at least a 30 % reduction from maximum baseline in iPTH level for 75 % of the patients receiving paricalcitol per dosing group . The study end point for efficacy was at least a 30 % reduction from maximum baseline in iPTH for 75 % of patients receiving paricalcitol per dosing group . Sixty-eight percent ( 15 of 22 ) of patients receiving paricalcitol attained this efficacy end point regardless of dosage received ( 0.04 , 0.08 , 0.16 , and 0.24 microg/kg ) . Eighty-three percent ( 5 of 6 ) of the patients in each of the paricalcitol groups receiving 0.16- and 0.24-microg/kg dosages attained the efficacy end point . Only two patients receiving placebo attained the iPTH end point . There were no clinical ly relevant differences in serum calcium ( Ca ) or phosphorus ( P ) levels between the group treated with paricalcitol and that treated with placebo . Although there was a statistically significant difference between the change from baseline to final-visit Ca levels in the paricalcitol group and the placebo group ( P < 0.001 ) , the final-visit mean Ca level in the paricalcitol group was within the normal range ( 9.44 mg/dL ) . There was no statistically significant difference between groups for the change from baseline in P level ( P = 0.625 ) . Only one patient treated with paricalcitol developed hypercalcemia before or coincident with the iPTH end point . Three other patients receiving paricalcitol experienced elevated serum Ca levels subsequent to reaching the iPTH end point , with iPTH reductions of 83 % to 98 % . There were no significant differences between patients treated with paricalcitol and patients treated with placebo in adverse reactions . These results show that paricalcitol safely and effectively reduces iPTH levels in hemodialysis patients with secondary HPT Background / Aims : Although the PTH-suppressive effect of intravenous calcitriol has already been demonstrated by various studies , the precise dose-response to calcitriol has not been fully determined for uremic secondary hyperparathyroidism ( 2HPT ) . In order to investigate in detail the dose-response of intravenous calcitriol and the adequate initial dose against 2HPT , a r and omized prospect i ve double-blind study was conducted . Method : One-hundred and sixty-two patients with 2HPT undergoing hemodialysis three times per week were r and omly assigned to four calcitriol ( Ro21 - 5535 ) treatment groups , 0 ( placebo ) , 1 , 1.5 or 2 µg . Calcitriol or placebo was given intravenously after each dialysis for 12 weeks under double-blind conditions . Results : Calcitriol dose-dependently reduced both intact-PTH and high-sensitivity assay mid-terminal (HS)-PTH levels . The rate of per-week change in intact-PTH was 0.0 % in the placebo group , –7.8 % in the 1-µg group , –18.9 % in the 1.5-µg group and –24.1 % in the 2-µg group . Calcitriol dose-dependently increased the rate of increase in serum Ca adjusted by albumin level . The per-week increases in adjusted serum Ca were –0.01 , 0.08 , 0.23 and 0.35 mg/dl in the placebo , 1- , 1.5- and 2-µg groups , respectively . Although the degree of PTH suppression was correlated with the adjusted serum Ca increase , by- patients investigation revealed that the number of patients with suppression of PTH despite of no or slight elevation of adjusted serum Ca level was largest in the 1-µg group among the three calcitriol groups . Conclusion : Intravenous calcitriol was found to have a clear dose-dependent effect on PTH reduction in patients with 2HPT , and the appropriate initial dose of this agent was determined to be 1 µg per dialysis session BACKGROUND Administration of intravenous ( i.v . ) calcitriol three times weekly effectively controls the synthesis and secretion of PTH in most uremic patients . Administration of a single dose of 1.25(OH)2D3 reduces synthesis of PTH-mRNA for 6 days in rats . Moreover , it can lower PTH levels for up to 4 days in chronic hemodialysis patients . Therefore , a good response to the administration of i.v . calcitriol two times weekly can be expected . We studied - in a multicenter r and omized study in patients with moderate to severe secondary hyperparathyroidism - the effects of the same doses of intravenous calcitriol , administered two or three times weekly . METHODS Twenty-two hemodialysis patients were r and omized into two frequencies of treatment groups : two times ( G-2/w ) and three times weekly ( G-3/w ) . Both groups were treated with increasing doses of intravenous calcitriol for 3 months ( first month 3 microg , second month 4 microg , third month 6 microg weekly ) . RESULTS After 12 weeks of therapy with intravenous calcitriol the G-2/w group showed a significant reduction in serum PTH levels ( from 821 + /- 392 to 350 + /- 246 pg/ml ; mean reduction = 57.4 % ) comparable to the decrease observed in the G-3/w group ( from 632 + /- 116 to 246 + /- 190 pg/ml ; mean reduction = 61.2 % ) . Ionized calcium ( G-2/w from 1.13 + /-0.10 to 1.14 + /- 0.08 and G-3/w 1.21 + /- 0.13 to 1.26 + /- 0.18 mmol/l ) and phosphate levels ( G-2/w from 4.99 + /- 1.01 to 5.99 + /- 1.78 and G-3/w 5.31 + /- 0.73 to 5.81 + /- 1.18 mg/dl ) did not change significantly and phosphate binders were not modified during the study . CONCLUSION This study confirms that intravenous calcitriol is an effective therapy for moderate to severe secondary hyperparathyroidism . The administration of two doses per week of intravenous calcitriol is as efficacious as three doses per week in suppressing PTH secretion BACKGROUND Calcitriol therapy is the mainstay of therapy for the treatment of secondary hyperparathyroidism . Oral administration of calcitriol is necessary in CAPD patients , but no studies have directly compared different routes of administration in this patient population . METHODS To determine if the peak serum calcitriol level ( pulse therapy ) is more important than the total delivered dose , we r and omized CAPD patients with mild to moderate secondary hyperparathyroidism to receive either pulse ( 3.0 microg twice a week , n = 10 ) or daily ( 0.75 microg a day , n = 8) oral calcitriol in comparable weekly doses . The main comparison was the rate of decline of serum intact parathyroid hormone ( PTH ) levels to reach the desired end-point of 100 pg/ml . The patients were dialysed with low-calcium dialysate and received only calcium-containing phosphate binders . RESULTS Pharmacokinetic analysis after a single dose of 3.0 microg ( pulse ) vs 0.75 microg ( daily ) revealed 1,25(OH)2-vitamin D levels to be higher in the pulse group at 3 and 6 h , but equivalent by 12 h. The area under the curve for 1 week of daily and 1 week of pulse therapy was equal . The patients in the 2 arms had equivalent basal serum levels of PTH ( pulse = 562 + /- 291 vs daily = 454 + /- 113 pg/ml ) , calcium ( pulse = 2.32 + /- 0.20 vs daily = 2.32 + /- 0.12 mmol/l ) and phosphorus ( pulse = 1.32 + /- 0.52 vs daily = 1.35 + /- 0.26 mmol/l ) . The time required for the PTH to decrease to 100 pg/ml and the rate of decline in PTH were similar ( time : pulse = 14.2 + /- 6.8 weeks , daily = 12.2 + /- 7 weeks ; rate : pulse = 7.4 + /- 4.2 vs daily = 8.4 + /- 4.2 % PTH/week ; P = NS ) . The serum calcium increased similarly in both groups . Hypercalcaemia ( > 2.9 mmol/l ) was rare ( pulse = 3 , daily = 2 episodes ) . CONCLUSIONS This study demonstrates that pulse and daily calcitriol are similarly effective and safe for the treatment of mild to moderate secondary hyperparathyroidism in CAPD patients despite higher peak levels of 1,25(OH)2-vitamin D with pulse therapy BACKGROUND Hemodialysis patients are at increased risk for progressive coronary artery calcification ; however , the development and progression of this disease process in patients new to hemodialysis is unknown . METHOD One hundred and twenty-nine patients new to hemodialysis were r and omized to receive calcium containing phosphate binders or the noncalcium phosphate binder sevelamer hydrochloride . Subjects underwent electron beam computed tomography scanning ( EBCT ) at entry into the study and again at 6 , 12 , and 18 months . RESULTS One hundred and nine patients underwent baseline and at least one additional assessment of coronary calcification . At baseline , 37 % of sevelamer treated and 31 % of calcium treated patients had no evidence of coronary calcification . No subject with a zero coronary artery calcium score ( CACS ) at baseline progressed to a CACS > 30 over 18 months . Subjects with a CACS > 30 at baseline showed progressive increases in CACS in both treatment arms ( P < 0.05 for each time point in both groups ) . Subjects treated with calcium containing phosphate binders showed more rapid and more severe increases in CACS when compared with those receiving sevelamer hydrochloride ( P= 0.056 at 12 months , P= 0.01 at 18 months ) . CONCLUSION New hemodialysis patients with no evidence of coronary calcification showed little evidence of disease development over 18 months independent of phosphate binder therapy . However , subjects with evidence of at least mild coronary calcification had significant progression at 6 , 12 , and 18 months . Use of calcium containing phosphate binders result ed in more rapid progression of coronary calcification than did use of sevelamer hydrochloride UNLABELLED We performed a post hoc analysis of a 52-week r and omized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer , a nonabsorbable polymer , on parameters of mineral metabolism and vascular calcification by electron beam tomography . In this analysis , we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover . Subjects r and omized to calcium salts experienced a significant reduction in trabecular bone attenuation and a trend toward reduction in cortical bone attenuation , in association with higher concentrations of serum calcium , lower concentrations of PTH , and reduced total and bone-specific alkaline phosphatase . INTRODUCTION In patients with chronic kidney disease , hyperphosphatemia is associated with osteodystrophy , vascular and soft tissue calcification , and mortality . Calcium-based phosphate binders are commonly prescribed to reduce intestinal phosphate absorption and to attenuate secondary hyperparathyroidism . Clinicians and investigators have presumed that , in hemodialysis patients , calcium exerts beneficial effects on bone . MATERIAL S AND METHODS We performed a post hoc analysis of a 52-week r and omized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer , a nonabsorbable polymer , on parameters of mineral metabolism and vascular calcification by electron beam tomography . In this analysis , we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover . RESULTS AND CONCLUSIONS The average serum phosphorus and calcium x phosphorus products were similar for both groups , although the average serum calcium concentration was significantly higher in the calcium-treated group . Compared with sevelamer-treated subjects , calcium-treated subjects showed a decrease in thoracic vertebral trabecular bone attenuation ( p = 0.01 ) and a trend toward decreased cortical bone attenuation . More than 30 % of calcium-treated subjects experienced a 10 % or more decrease in trabecular and cortical bone attenuation . On study , sevelamer-treated subjects had higher concentrations of total and bone-specific alkaline phosphatase , osteocalcin , and PTH ( p < 0.001 ) . When used to correct hyperphosphatemia , calcium salts lead to a reduction in thoracic trabecular and cortical bone attenuation . Calcium salts may paradoxically decrease BMD in hemodialysis patients Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia and aluminum-based binders that result in total body aluminum accumulation over time . This investigation describes the use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis patients and compares it with a st and ard calcium-based phosphate binder . An open-label , r and omized , crossover study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients . After a 2-week phosphate binder washout period , stable hemodialysis patients were administered either sevelamer or calcium acetate , and the dosages were titrated upward to achieve improved phosphate control over an 8-week period . After a 2-week washout period , patients crossed over to the alternate agent for 8 weeks . Eighty-four patients from eight centers participated in the study . There was a similar decrease in serum phosphate values over the course of the study with both sevelamer ( -2.0 + /- 2.3 mg/dL ) and calcium acetate ( -2.1 + /- 1.9 mg/dL ) . Twenty-two percent of patients developed a serum calcium greater than 11.0 mg/dL while receiving calcium acetate , versus 5 % of patients receiving sevelamer ( P < 0.01 ) . The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period . Patients treated with sevelamer also sustained a 24 % mean decrease in serum low-density lipoprotein cholesterol levels . Sevelamer was effective in controlling hyperphosphatemia without result ing in an increase in the incidence of hypercalcemia seen with calcium acetate . This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients , and its usage may be advantageous in the treatment of dialysis patients In a double-blind controlled study , 15 patients received 1,25-dihydroxycholecalciferol ( 1,25[OH]2D3 ) ( 0.5 - 1.5 microgram/day ) and 16 patients received vitamin D3 ( D3 ) ( 400 - 1,200 IU/day ) . The patients receiving 1,25(OH)2D3 had a rise in mean serum calcium concentration from 9.05 + /- 0.15 to 10.25 + /- 0.20 mg/dl ( p less than .001 ) with a return to 9.37 + /- 0.16 ( p less than .001 ) in the post-control period ; however , hypercalcemia ( greater than 11.5 mg/dl ) occurred in 5 of 15 patients . Likewise , patients who received 1,25(OH)2D3 but not those given D3 had a reversible decrease in immunoreactive parathyroid levels . 9 of 12 patients given D3 had serial iliac crest bipsies showing histologic deterioration , while 6 of 7 patients who received 1,25(OH)2D3 were improved or unchanged ( p less than 0.025 ) . Bone mineral and calcium content decreased in patients on D3 ( p less than .05 ) but not in those on 1,25(OH)2D3 . We conclude that the administration of 1,25(OH)2D3 to dialysis patients : ( 1 ) has a calcemic effect . ( 2 ) decreases levels of immunoreactive parathyroid hormone , and ( 3 ) is associated with histologic improvement in bone disease Background / Aims : Hyperphosphatemia is an important clinical consequence of renal failure , and its multiple adverse systemic effects are associated with significantly increased risks of morbidity and mortality in dialysis patients . Existing oral phosphate binders have not permitted control of serum phosphate within currently accepted guidelines . This study compares lanthanum carbonate with calcium carbonate for control of serum phosphate in hemodialysis patients . Methods : In this European multicentre study , 800 patients were r and omised to receive either lanthanum or calcium carbonate and the dose titrated over 5 weeks to achieve control of serum phosphate . Serum levels of phosphate , calcium and parathryoid hormone were followed over the following 20 weeks . Results : Around 65 % of patients in each group achieved phosphate control , but in the calcium carbonate group this was at the expense of significant hypercalcemia ( 20.2 % of patients vs. 0.4 % ) . Consequently , calcium x phosphate product tended to be better controlled in the lanthanum group . Conclusion : This 6-month study demonstrates that serum phosphate control with lanthanum carbonate ( 750–3,000 mg/day ) is similar to that seen with calcium carbonate ( 1,500–9,000 mg/day ) , but with a significantly reduced incidence of hypercalcemia . Lanthanum carbonate is well tolerated and may be more effective in reducing calcium x phosphate product than calcium carbonate BACKGROUND Calcitriol lowers parathyroid hormone ( PTH ) levels in patients with chronic kidney disease ( CKD ) stages 3 and 4 , but its use is limited by a low therapeutic index and concerns regarding hypercalcemia and acceleration of kidney disease . We evaluated doxercalciferol ( 1alpha-hydroxyvitamin D2 ) as an alternative therapy in a r and omized , double-blinded , placebo-controlled , multicenter trial . METHODS Fifty-five adults with stage 3 or 4 CKD and an intact PTH ( iPTH ) level greater than 85 pg/mL ( ng/L ) completed 8 baseline weeks , followed by 24 weeks of oral therapy with doxercalciferol or placebo . Pretreatment demographics and biochemical features did not differ between groups . Dosages were increased gradually if iPTH level was not decreased by 30 % or greater and serum calcium and phosphorus levels were stable . Regular monitoring included plasma iPTH , serum calcium and phosphorus , urinary calcium , bone-specific serum markers , and serum lalpha,25-dihydroxyvitamin D levels . Glomerular filtration rate ( GFR ) was measured before and after treatment . RESULTS Mean plasma iPTH level decreased by 46 % from baseline after 24 weeks of doxercalciferol treatment ( P < 0.001 ) , but was unchanged with placebo . After 6 weeks , iPTH level reductions with doxercalciferol treatment exceeded those with placebo at all subsequent intervals ( P < 0.001 ) . No clinical ly significant differences in mean serum calcium or phosphorus or urinary calcium levels or incidence of hypercalcemia , hyperphosphatemia , or hypercalciuria were noted between groups . Serum C- and N-telopeptide and bone-specific alkaline phosphatase levels decreased with doxercalciferol treatment relative to both baseline and placebo ( P < 0.01 ) . Adverse-event rates and changes in GFR did not differ between groups . CONCLUSION Doxercalciferol is safe and effective in controlling secondary hyperparathyroidism of patients with CKD stages 3 and 4 BACKGROUND Calcitriol is widely used in conjunction with phosphorus-binders containing calcium to treat secondary hyperparathyroidism in dialysis patients . Its efficacy in patients with severe hyperparathyroidism is diminished , in part , due to gl and ular hyperplasia associated with decreased calcitriol and calcium receptors . SUBJECTS AND METHODS We , therefore , developed a prospect i ve , r and omized trial comparing i.v . calcitriol plus calcium carbonate ( CaCO3 ) compared to CaCO3 alone ( control ) in patients with mild to moderate hyperparathyroidism who were within the first year of initiating hemodialysis . Patients underwent calcium ( Ca ) suppression/stimulation testing at baseline and after six and twelve months of treatment to indirectly assess parathyroid gl and hyperplasia . RESULTS In the calcitriol group , the amino-terminal parathyroid hormone ( N-PTH ) decreased significantly from a baseline value of 70 + /- 12 pg/ml at month zero to 22 + /- 7 and 19 + /- 6 pg/ml at months 6 and 12 , respectively ( the conversion factor of amino-terminal PTH to intact PTH is 6 , i.e. , 10 pg/ml N-PTH equals 60 pg/ml intact PTH ) . In contrast , the N-PTH levels in the CaCO3 alone group did not change . The change in nadir N-PTH levels at month 12 compared to month zero decreased by 14 + /- 7 % in the calcitriol group but increased by 96 + /- 59 % in the control group ( p < 0.05 ) . In addition , the increment in N-PTH levels during hypocalcemic stimulation decreased by 68 + /- 6 % at month 12 compared to month zero but increased by 61 + /- 42 % in the control group . Although total calcium and phosphorus levels were not different between the two groups , ionized calcium values were higher in the calcitriol group . The incidence of hypercalcemia was the same in both groups and the episodes were asymptomatic . CONCLUSION Pulse calcitriol therapy is effective in preventing progression of secondary hyperparathyroidism in hemodialysis patients with mild to moderate disease . Based on Ca suppression/stimulation tests , calcitriol was more successful in preventing gl and growth than CaCO3 alone . Further studies are needed to determine if the strategy of early treatment of mild to moderate hyperparathyroidism by pulse calcitriol is safe and effective in hemodialysis in patients We report on a 5-year , prospect i ve , double-blind trial of 1,25 dihydroxycholecalciferol ( calcitriol ) versus placebo in 76 hemodialysis patients without biochemical or radiological evidence of bone disease . Calcitriol , 1 microgram daily , regularly induced hypercalcemia . Doses of 0.25 microgram daily or less proved satisfactory in most patients . During calcitriol treatment , plasma calcium concentration was significantly higher and serum parathyroid hormone concentration significantly lower than on placebo . There was no difference in the rates of development or of progression of vascular calcification in the two groups . Significantly more patients on placebo ( 17 vs. 6 , p less than 0.05 ) developed a sustained elevation of plasma alkaline phosphatase concentration . Calcitriol appeared to protect against the development of histological evidence of osteitis fibrosa but not of osteomalacia , but accumulation of aluminum in bone occurred during the study . We conclude that calcitriol delays and may prevent the development of osteitis fibrosa in patients receiving regular hemodialysis and may reasonably be prescribed routinely in hemodialysis patients without biochemical or radiological abnormality , unless there is a substantial prospect of early renal transplantation BACKGROUND Treatment of secondary hyperparathyroidism with vitamin D and calcium in patients receiving dialysis is often complicated by hypercalcemia and hyperphosphatemia , which may contribute to cardiovascular disease and adverse clinical outcomes . Calcimimetics target the calcium-sensing receptor and lower parathyroid hormone levels without increasing calcium and phosphorus levels . We report the results of two identical r and omized , double-blind , placebo-controlled trials evaluating the safety and effectiveness of the calcimimetic agent cinacalcet hydrochloride . METHODS Patients who were receiving hemodialysis and who had inadequately controlled secondary hyperparathyroidism despite st and ard treatment were r and omly assigned to receive cinacalcet ( 371 patients ) or placebo ( 370 patients ) for 26 weeks . Once-daily doses were increased from 30 mg to 180 mg to achieve intact parathyroid hormone levels of 250 pg per milliliter or less . The primary end point was the percentage of patients with values in this range during a 14-week efficacy- assessment phase . RESULTS Forty-three percent of the cinacalcet group reached the primary end point , as compared with 5 percent of the placebo group ( P<0.001 ) . Overall , mean parathyroid hormone values decreased 43 percent in those receiving cinacalcet but increased 9 percent in the placebo group ( P<0.001 ) . The serum calcium-phosphorus product declined by 15 percent in the cinacalcet group and remained unchanged in the placebo group ( P<0.001 ) . Cinacalcet effectively reduced parathyroid hormone levels independently of disease severity or changes in vitamin D sterol dose . CONCLUSIONS Cinacalcet lowers parathyroid hormone levels and improves calcium-phosphorus homeostasis in patients receiving hemodialysis who have uncontrolled secondary hyperparathyroidism The effects of a small dose of calcitriol ( less than or equal to 0.50 micrograms/day ) on parathyroid and renal function , bone histomorphometry , and aluminum ( Al ) metabolism were studied in a r and omized double blind study of 30 patients with predialysis chronic renal failure . The patients were followed at least monthly for 8 months . Serum Al levels were measured , and transiliac bone biopsies , double labeled with tetracycline , were obtained at both the beginning and end of the 8-month treatment period . Serum calcium and ionized calcium concentrations increased in the treatment group , and the calcitriol dosage had to be reduced in 8 patients at least once because of hypercalcemia . Calcitriol treatment did not significantly influence either serum A1 levels or the presence of stainable Al in bone . Serum PTH , urinary cAMP excretion , and bone resorption indices decreased in the treatment group , indicating suppression of parathyroid hyperfunction . Throughout the study renal function decreased at a similar rate in both groups , suggesting that calcitriol treatment had no depressive effect on renal function . We conclude that a low dose of calcitriol may be used to preserve or even restore bone metabolism in patients with predialysis chronic renal failure if serum calcium is closely followed and hypercalcemia promptly treated The suppressive effects of intravenous ( IVC ) and oral ( ORC ) 1,25(OH)2D3 ( calcitriol ) therapies on parathyroid hormone ( PTH ) secretion were compared in 10 hemodialysis ( HD ) patients with secondary hyperparathyroidism ( SHPT ) . These patients were r and omized to receive either IVC or ORC therapy for 12 weeks , both followed by a 12-week washout period . After the washout , the patients who received IVC then switched to ORC therapy for another 12 weeks , and the patients who received ORC switched to IVC therapy . The mean dose of IVC was 2.45 + /- 0.30 micrograms/dialysis session ( approximately equal to 1.05 micrograms/day ) and that of ORC was 0.69 + /- 0.07 micrograms/day . A significant reduction in serum levels of intact PTH was observed after 8 weeks and that of C-PTH after 10 weeks of ORC therapy , but both fell after 6 weeks of IVC treatment . There was a concomitant reduction in serum alkaline phosphatase ( AP ) , but it became significant 4 weeks later than in intact PTH . The maximal reductions of serum levels of intact PTH , C-PTH and AP were 74.28 , 64.91 , 41.97 % , respectively , after IVC , and 31.57 , 24.39 , 22.50 % , respectively , after ORC therapy . Serum calcium rose faster during ORC treatment . There were no significant changes in serum levels of phosphorus , magnesium , and albumin throughout the treatment period . We conclude that both IVC or ORC treatments result in a significant decrement in blood levels of PTH in chronic HD patients with SHPT . However , this PTH-suppressive effect is more pronounced with IVC therapy , and can not be totally explained by either the higher dose or elevated serum calcium Calcitriol has shown a benefit in various small uncontrolled studies of ex vivo immune function . We hypothesized that paricalcitol , a new vitamin D derivative , will have a positive effect on the immune system with minimal adverse effects on calcium homeostasis . Thirty-one hemodialysis patients not administered vitamin D because of low intact parathyroid hormone ( PTH ) levels were r and omized to placebo or 4 microg of paricalcitol intravenously with the hemodialysis session three times weekly for 12 weeks . Effects on in vivo and ex vivo assessment s of immune function were evaluated . All patients achieved the target dose of paricalcitol . Twenty patients were anergic at the start of the study ; 4 of 11 patients in the paricalcitol group and 0 of 9 patients in the placebo group converted to reactive ( P = 0.09 ) . The in vivo response to st and ard hepatitis B booster vaccine and in vitro proliferation and release of interleukin-2 ( IL-2 ) , IL-6 , tumor necrosis factor-alpha , and interferon-gamma from stimulated lymphocytes were not different between the groups . In contrast to clinical immune effects , paricalcitol increased serum calcium levels and decreased PTH and bone alkaline phosphatase levels ( all P < 0.05 ) . However , hypercalcemia was infrequent . In vitro experiments showed that paricalcitol led to greater dose-dependent thymidine uptake than calcitriol in lymphocytes isolated from either dialysis patients or control subjects . Paricalcitol has a tendency toward improving delayed hypersensitivity reactions , but did not have other proimmune effects . However , as expected , paricalcitol had significant effects on calcium homeostasis compared with placebo . Thus , patients with low PTH levels are unlikely to experience the proimmune effects of vitamin D therapy without more profound and potentially adverse oversuppression of PTH BACKGROUND Lanthanum carbonate is a novel , non-calcium , non-aluminum phosphate binder under evaluation for the treatment of hyperphosphatemia in end-stage renal disease ( ESRD ) patients receiving either hemodialysis or continuous ambulatory peritoneal dialysis . METHODS This 16-week study assessed the control of serum phosphorus with lanthanum carbonate , and its effects on serum calcium , calcium x phosphorus product , and parathyroid hormone ( PTH ) . Hemodialysis patients > or = 18 years old entered into a 1- to 3-week washout period during which serum phosphorus levels rose to > 5.9 mg/dL ( 1.90 mmol/L ) . In total , 126 patients were titrated with lanthanum carbonate at doses containing 375 , 750 , 1,500 , 2,250 , or 3,000 mg/d elemental lanthanum , given in divided doses with meals over a 6-week period , to achieve serum levels < or = 5.9 mg/dL. By the end of dose titration , 11/126 ( 9 % ) patients received < or = 750 mg/d of lanthanum , 25 ( 20 % ) received 1,500 mg/d , 37 ( 29 % ) received 2,250 mg/d , and 53 ( 42 % ) received 3,000 mg/d . Following titration , patients were r and omized to receive either lanthanum carbonate or placebo during a 4-week , double-blind maintenance phase . RESULTS At the study endpoint , the mean difference in serum phosphorus between the lanthanum carbonate and placebo treatment arms was 1.91 mg/dL ( 0.62 mmol/L ) ( P < 0.0001 ) . Calcium x phosphorus product ( P < 0.0001 ) and serum PTH levels ( P < 0.01 ) were also significantly lower with lanthanum carbonate versus placebo . The incidence of drug-related adverse events was similar between placebo- and lanthanum carbonate-treated patients . CONCLUSION Lanthanum carbonate is an effective and well-tolerated agent for the treatment of hyperphosphatemia in patients with ESRD BACKGROUND Lanthanum carbonate ( LC ) ( Fosrenol ) is a novel new treatment for hyperphosphatemia . In this phase III , open-label study , we compared the effects of LC and calcium carbonate ( CC ) on the evolution of renal osteodystrophy ( ROD ) in dialysis patients . METHODS Ninety-eight patients were r and omized to LC ( N = 49 ) or CC ( N = 49 ) . Bone biopsies were taken at baseline and after one year of treatment . Acceptable paired biopsies were available for static and dynamic histomorphometry studies in 33 LC and 30 CC patients . Blood sample s were taken at regular intervals for biochemical analysis and adverse events were monitored . RESULTS LC was well tolerated and serum phosphate levels were well controlled in both treatment groups . The incidence of hypercalcemia was lower in the LC group ( 6 % vs. 49 % for CC ) . At baseline , subtypes of ROD were similarly distributed in both groups , with mixed ROD being most common . At one-year follow-up in the LC group , 5 of 7 patients with baseline low bone turnover ( either adynamic bone or osteomalacia ) , and 4 of 5 patients with baseline hyperparathyroidism , had evolved toward a normalization of their bone turnover . Only one lanthanum-treated patient evolved toward adynamic bone compared with 6 patients in the CC group . In the LC group , the number of patients having either adynamic bone , osteomalacia , or hyperpara decreased overall from 12 ( 36 % ) at baseline to 6 ( 18 % ) , while in the calcium group , the number of patients with these types of ROD increased from 13 ( 43 % ) to 16 ( 53 % ) . CONCLUSION LC is a poorly absorbed , well-tolerated , and efficient phosphate binder . LC-treated dialysis patients show almost no evolution toward low bone turnover over one year ( unlike CC-treated patients ) , nor do they experience any aluminum-like effects on bone We conducted a 7‐month r and omized , single , double , single‐blind comparison of calcitriol ( 1,25(OH)2D3 ) with vitamin D3 in 22 hemodialysis patients to study the effects on the biochemical abnormalities associated with osteodystrophy . Calcitriol was given for 3 mo . All patients had initial pre study calcium values ≤9.5 mg/100 ml , and phosphate values ≤4.5 mg/100 ml . Data were analyzed using the Normalized Trend Index ( NTI ) . Calcitriol induced a rise in calcium ( 8.7 to 10.25 mg/100 ml ) ( p < 0.001 ) and a fall in alkaline phosphatase ( p < 0.005 ) , while D3 had no appreciable effect . The mean dose of calcitriol during treatment was 0.579 µg/day while that for D3 was 706 IU/day . The effect on serum phosphate concentration was variable . Hypercalcemia as high as 13.2 mg/100 ml occurred in 2 of 13 patients on 1,25(OH)2D3 , but in every instance promptly returned to normal with dose reduction . No other adverse effects were noted with therapy . We conclude that calcitriol reverses the biochemical abnormalities of osteodystrophy . Since its effects are rapidly reversed with discontinuation , the drug is probably safe as well as effective To assess the effect of the different modes of calcitriol administration on PTH-ionized calcium relationship we conducted a prospect i ve clinical trial in 33 patients on chronic haemodialysis with secondary hyperparathyroidism ( four times upper normal limit intact PTH ) who were r and omly assigned , with stratification to PTH levels , to receive daily oral , intermittent oral , or intermittent intravenous calcitriol at the same dose of 0.045 micrograms/kg/weekly . PTH-iCa curves were generated by inducing hypo- or hypercalcaemia in sequential haemodialysis 1 week apart , before and after 10 weeks on treatment . All patients were dialysed against a dialysate calcium concentration of 2.5 mEq/l throughout the study period . After drop-outs , 26 patients completed the study : 11 on intravenous calcitriol ( mean basal PTH + /- SD : 666 + /- 280 pg/ml ) , eight on intermittent oral calcitriol ( mean basal PTH : 831 + /- 361 ) , and seven on daily oral calcitriol ( mean basal PTH : 719 + /- 280 ) . Serum ionized calcium and phosphorus significantly increased in intravenous and daily oral groups after calcitriol treatment , but not in the intermittent oral group . Basal PTH did not significantly change in the three groups after 10 weeks on treatment . Maximal PTH significantly decreased in intravenous group ( 1449 + /- 660 versus 1122 + /- 691 pg/ml , P = 0.0085 ) and at the limit of statistical significance in the intermittent oral group ( 1701 + /- 774 versus 1445 + /- 634 , P = 0.12 ) , but it did not change in the daily oral group . Minimal PTH did not modify in the three groups . In all three groups , a shift to the right in the PTH-iCa relationships were observed , with significant changes in the set point of calcium . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of this prospect i ve and r and omized study was to compare the efficacy , side effects , and costs of ' pulse oral ' versus intravenous calcitriol in the treatment of secondary hyperparathyroidism in hemodialysis ( HD ) patients . A total of 20 patients were r and omized to receive over a 4-month period pulse orally administered calcitriol ( pulse oral group ; n = 10 ) or intravenous calcitriol ( intravenous group ; n = 10 ) . All patients used st and ard dialysate calcium ( 1.75 mmol/l ) throughout the study period . In accordance with the study design calcium dialysate concentrations were reduced when this was necessary to avoid hypercalcemic crises . The patients were stratified into two subgroups according to their initial serum PTH levels : patients with mild or moderate degree of hyperparathyroidism ( 17 patients ) and patients with severe hyperparathyroidism ( 3 patients ) . Intravenous and pulse oral cacitriol did not significantly reduce serum PTH concentrations in patients with severe hyperparathyroidism ( 1,157 + /- 156 vs. 807 + /- 228 pg/ml [ corrected ] , p = 0.09 ) . Intermittent calcitriol , administered by intravenous or oral route , significantly reduced serum PTH levels ( 326 + /- 119 vs. 109 + /- 79 pg/ml [ corrected ] , p = 0.0001 ) in patients with mild or moderate hyperparathyroidism . In patients with mild or moderate hyperparathyroidism , intravenous calcitriol significantly reduced PTH concentrations at the end of the 1st month , before the increase of serum ionized calcium levels , whereas ' pulse oral ' calcitriol significantly suppressed parathyroid activity at the end of the 2nd month . Calcium dialysate concentration was reduced in 9 out of 10 ( 90 % ) patients of the pulse oral group and in all patients ( 10/10 ) of intravenous group . The incidence of hypercalcemic crises was 24 % ( 39/160 ) in the pulse oral group and 14 % ( 27/160 ) in the intravenous group . Analysis of costs showed that intravenous calcitriol was more expensive compared to pulse oral calcitriol . These data indicate that intermittent intensive calcitriol therapy , regardless of the route of administration , is effective in suppressing parathyroid activity in HD patients with mild or moderate hyperparathyroidism . In contrast , intermittent calcitriol therapy has a limited ability to achieve sustained serum PTH reductions in HD patients with severe hyperparathyroidism . Intravenous calcitriol was more expensive than pulse oral calcitriol , and we recommend the use of pulse oral calcitriol in HD patients with mild or moderate secondary hyperparathyroidism 27 patients on hemodialysis ( dialysate aluminium less than 0.7 mumol/l for 2 years , and 2 mumol/l before ) whose plasma Ca and PO4 were adequately controlled for already 6 months by high doses of CaCO3 alone ( mean + /- SD : 9 + /- 5 g/day ) , were r and omly divided into 2 groups , a control group ( c group ) which was kept on the same treatment , and a group in which CaCO3 was reduced to 3 g/day but in which plasma Ca was kept normal due to 1 alpha-OH-vitamin D3 administration ( 1 microgram/day at the beginning , 0.3 microgram/day after 6 months ; 1 alpha group ) whereas plasma phosphate was kept below 6.0 mg/dl because of Al(OH)3 ( 2.7 - 5 g/day ) . Initially , the 2 groups were comparable as regards the plasma concentrations of total and ionized Ca , phosphate , alkaline phosphatases , medium and C-terminal parathyroid hormone ( PTH ) and aluminium , but the control group had lower plasma 25-OH-vitamin D ( 25-OHD . ) After 6 months , the same difference in plasma 25-OHD was found with comparable plasma concentrations of total and ionized calcium as well as of medium and C-terminal PTH ( beta error 1 % ) . However , plasma concentration of phosphate and the plasma Ca phosphate product , as well as the plasma aluminium were higher in the 1 alpha group whereas their PCO3H- was lower . Although the alkaline phosphatase values were not significantly different between the 2 groups , they increased only in the control group because of 1 patient who developed a vitamin-D-deficient osteomalacia ( plasma 25-OHD 3 ng/ml ) , which was subsequently cured by physiological doses of 25-OHD3 . The incidence of transient hypercalcemia ( 15 vs. 21 episodes ) and worsening of soft tissue calcifications ( 3 in each group ) was the same in the 2 groups In the present study , we compared the efficacy of two intravenous forms of vitamin D3[Calcijex : 1,25(OH)2D3 and One-Alpha : 1(OH)D3 ] and that of oral One-Alpha in the treatment of secondary hyperparathyroidism in patients receiving maintenance hemodialysis . Twenty patients were assigned to 1 of 2 treatment groups ( A and B ) which were matched for age , sex , and duration of maintenance hemodialysis . None of the patients included had chronic liver disease or had received drugs known to interfere with hepatic enzymes . All patients had received a stable dose of oral calcium and One-Alpha for a minimum period of 1 year , which maintained corrected serum calcium at the upper limit of the normal range . At the start of the study , oral One-Alpha was replaced by Calcijex in group A and injectable One-Alpha in group B. Treatment was maintained for 3 months ( phase I ) . Subsequently , injectable vitamin D3 was discontinued and all patients received their previous dose of oral One-Alpha for a period of 1 month . Finally , oral One-Alpha was discontinued again and the injectable forms of vitamin D3 were crossed over in the 2 treatment groups for another 3 months ( phase II ) . The results showed that the serum concentrations of 1,25(OH)2D3 , measured 48 h after intravenous injection of One-Alpha , were not different from that produced by an equivalent dose of Calcijex in the same group of patients . Furthermore , overall analysis of intact parathyroid levels during the cross-over , using ANOVA with repeated responses , indicated that the two analogues were equipotent as regards suppression of PTH secretion . In our study , treatment with intravenous vitamin D3 led to significant suppression of PTH secretion . These results were achieved by a lower drug dosage of vitamin D3 and at lower trough blood levels of 1,25(OH)2D3 as compared to those of oral One-Alpha . Our findings are in favor of the early use of either forms of injectable vitamin D3 in the treatment of secondary hyperparathyroidism Vitamin D therapy for patients with end-stage renal disease ( ESRD ) on hemodialysis therapy has relied on patient dry weight to determine the initial dose of medication . Obtaining a patient 's dry weight can be difficult , and no correlation has been established between a patient 's body weight and severity of secondary hyperparathyroidism . We conducted a double-blind , double-dummy , r and omized , 12-week , multicenter trial to compare the incidence of hypercalcemia ( single occurrence ) between two dosing regimens : one regimen based on baseline intact parathyroid hormone ( iPTH ; PTH/80 ) level , and the other regimen based on patient body weight ( 0.04 microgram/kg ) . One hundred twenty-five adult patients with ESRD on maintenance hemodialysis therapy were enrolled at multiple sites . Before treatment , all patients were required to have PTH levels of 300 pg/mL or greater , calcium levels of 8.0 mg/dL or greater and 10.5 mg/dL or less , and a calcium x phosphorus ( Ca x P ) product of 70 or less . Patients were r and omized to one of two regimens : the nonr and omized treatment was also administered as a placebo dummy . No incidence of hypercalcemia occurred in either treatment group during the study . Patients treated according to the formula iPTH/80 required fewer dose adjustments and achieved the first of four consecutive reductions from baseline PTH level of 30 % or greater more rapidly than patients treated based on body weight ( P = 0.0306 ) . Incidences of elevated Ca x P product levels were similar between treatment groups . Treatment with paricalcitol injection based on degree of secondary hyperparathyroidism incurred no greater risk for hypercalcemia and achieved meaningful therapeutic results with fewer dose adjustments than dosing based on patient body weight |
1,676 | 30,157,133 | The results indicate that epidermal nerve fiber loss , in isolation , is not a useful indicator of painful symptoms or their severity in DSP .
Intraepidermal nerve fiber density correlated reasonably well with neuropathy scores on tools assessing signs and symptoms ( such as the Michigan Neuropathy Screening Instrument and the Total Neuropathy Score ) , but less so with symptom measures only .
Among various psychophysical sensory measures , warmth detection and heat pain thresholds correlated best with intraepidermal nerve fiber density , particularly when assessed at the same anatomical site . | Abstract The diagnosis of distal symmetric polyneuropathies ( DSPs ) relies on the presenting symptomatology and neurological sensory examination , supported by objective ly quantified structural and functional changes in sensory nerves .
Although these separate components have important diagnostic utility , the associations between the structural vs the symptomatic and functional findings in painful DSP are still unclear .
It is assumed that delineation of the correlations , or lack of such , between structure , clinical presentation , and function will contribute to a better underst and ing and treatment of DSP . | A r and omized , double-blind , placebo-controlled study of brain-derived neurotrophic factor ( rhBDNF ) was conducted in 30 patients with insulin-treated diabetes mellitus , with obligatory abnormalities of sural nerve conduction studies and vibration perception threshold ( VPT ) at the great toe on recruitment . Nine patients received placebo , 11 rhBDNF ( 25 microg/ kg ) and 10 rhBDNF ( 100 microg/kg ) s.c . daily for 3 months , and were assessed at days 0 , 8 , 15 , 29 , 43 , 57 and 85 with nerve conduction and quantitative sensory and autonomic tests including VPT , thermal and light touch thresholds , and cutaneous axon-reflexes . No statistically significant differences were found among the 3 treatment groups between baseline and day 85 values . To examine possible reasons for lack of effect , post hoc analysis was performed . In the subset of patients with abnormal but detectable cool detection threshold ( CDT ) at baseline , there was improvement of CDT at day 85 when compared to baseline in the treated ( p < 0.02 ) but not placebo group . Further , from days 43 to 85 , in the treated group but not the placebo group , CDT was indistinguishable from a group of matched normal subjects ( p > 0.05 ) . Skin biopsies failed to show evidence of structural change ; assessment of innervation of hair follicles , which is partly dependent on BDNF , was not possible because of the marked loss of this end-organ in diabetic neuropathic skin . The only side effects of rhBDNF were infrequent non-painful injection-site skin reactions and increased gut motility at the higher dose . We conclude that further pre clinical studies are warranted before any future clinical trials to see if rhBDNF improves CDT and constipation in diabetics Background : The Norfolk Quality of Life Question naire-Diabetic Neuropathy ( Norfolk QOL-DN ) is a vali date d comprehensive question naire design ed to capture the entire spectrum of DN related to large fiber , small fiber , and autonomic neuropathy not captured in existing instruments . We aim ed to determine if the Norfolk QOL-DN could be used to capture changes in QOL that correlate with nerve fiber-specific objective measures in a placebo-controlled trial of two agents that affect different nerve fibers . Methods : Sixty patients with DN were allocated to treatment on ruboxistaurin ( RBX ) ( n = 18 ) , topiramate ( TPX ) ( n = 18 ) , or placebo ( n = 18 ) . QOL-DN was administered and objective measures of nerve function were performed at entry and end of the study period . Results : Total QOL scores improved significantly in the active treatment groups ( RBX −9.56 ± 4.13 ; TPX −12.22 ± 2.76 ) but not in placebo ( −5.56 ± 3.49 ) . There were differences in nerve function improvement between treatments . Neurological symptom scores ( NSS ) improved with TPX from 5.5 ( 2.3 ) to 4.3 ( 0.65 ) ( p = .007 ) , sensory scores improved with TPX from 15.5 ( 1.79 ) to 8.3 ( 1.19 ) ( p < .001 ) , motor scores did not change , and sensory and motor impairment scores improved with TPX from 18.8 ( 2.15 ) to 12.1 ( 1.71 ) ( p = .003 ) . Total neuropathy scores ( TNS ) improved with TPX from 24.35 ( 2.61 ) to 16.35 ( 2.02 ) ( p = .001 ) . Neuropathy total symptom score−6 ( NTSS−6 ) changes were significant for both treatments : RBX 4.38 ( 0.75 ) to 1.49 ( 0.38 ) ( p < .001 ) and TPX 7.57 ( 1.3 ) to 4.26 ( 0.95 ) ( p = .036 ) . Changes in QOL-DN large fiber subscores correlated ( Spearman 's rank ) significantly with changes in NTSS-6 ( r = 0.55 ; p < .0001 ) , NSS ( r = 0.31 ; p < .04 ) , neuropathy impairment score ( NIS ) ( r = 0.35 ; p < .02 ) , and TNS ( r = 0.48 ; p < .0006 ) . Changes in QOL-DN small fiber subscores correlated significantly with changes in NTSS-6 total scores ( r = 0.40 ; p < .005 ) and intraepidermal nerve fiber density ( IENFD ) ( r = −0.29 ; p < .05 ) . Conclusion : Ruboxistaurin produced significant improvement in large fiber measures while TPX produced significant changes in small fiber measures . The Norfolk QOL-DN tool differentiated between these changes captured in the fiber-specific domains . Correlations were found between objective measures of neuropathy and total QOL , but those with nerve fiber domain scores were modest and reinforce the need to quantify QOL as an endpoint in neuropathy independent of other measures Summary The role of afferent sensory input in neuropathic pain was examined in 2 groups . Peripheral nerve blocks abolished spontaneous and evoked pain in all patients . Systemic lidocaine was more effective in pain due to polyneuropathy than nerve injury . Central sensitization does not act as an autonomous spontaneous pain‐generating mechanism . Peripheral sensory input is critical in maintaining pain after peripheral nerve damage . ABSTRACT Central sensitization after peripheral nerve injury may result in ectopic neuronal activity in the spinal cord dorsal horn , implying a potential autonomous pain‐generating mechanism . This study used peripheral nerve blockade and systemic lidocaine administration , with detailed somatosensory assessment , to determine the contribution of primary afferent input in maintaining peripheral neuropathic pain . Fourteen patients with neuropathic pain ( 7 with unilateral foot pain due to peripheral nerve injury and 7 with bilateral pain in the feet due to distal polyneuropathy ) underwent comprehensive characterization of somatosensory function by quantitative sensory testing . Patients were then administered an ultrasound‐guided peripheral nerve block with lidocaine and intravenous lidocaine infusion in r and omized order . The effect of these interventions on spontaneous pain intensity and on evoked cold , warm , pinprick , and brush responses was assessed at each session . All patients had sensory disturbances at baseline . The peripheral nerve block result ed in a complete abolition of ipsilateral pain within 10 min ( median ) in all patients , with lidocaine plasma concentrations being too low to account for a systemic effect of the drug . Intravenous lidocaine infusion reduced the spontaneous pain by 45.5 % ( ±31.7 % ) , and it reduced mechanical and thermal hypersensitivity in most patients who displayed such signs . However , the improvement in evoked hypersensitivity was not related to the effect of the drug on spontaneous pain intensity . This study demonstrated that regardless of the individual somatosensory phenotype and signs of central sensitization , primary afferent input is critical for maintaining neuropathic pain in peripheral nerve injury and distal polyneuropathy Background Fabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy . We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials ( PREP ) . Methods In this case – control study we prospect ively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology . Data were compared with healthy controls using non-parametric statistical tests . All patients underwent neurological examination and were investigated with pain and depression question naires . Small fiber function ( quantitative sensory testing , QST ) , morphology ( skin punch biopsy ) , and electrical conduction ( PREP ) were assessed and correlated . Patients were stratified for gender and disease severity as reflected by renal function . Results All Fabry patients ( 31 men , 45 women ) had small fiber neuropathy . Men with Fabry disease showed impaired cold ( p < 0.01 ) and warm perception ( p < 0.05 ) , while women did not differ from controls . Intraepidermal nerve fiber density ( IENFD ) was reduced at the lower leg ( p < 0.001 ) and the back ( p < 0.05 ) mainly of men with impaired renal function . When investigating A-delta fiber conduction with PREP , men but not women with Fabry disease had lower amplitudes upon stimulation at face ( p < 0.01 ) , h and s ( p < 0.05 ) , and feet ( p < 0.01 ) compared to controls . PREP amplitudes further decreased with advance in disease severity . PREP amplitudes and warm ( p < 0.05 ) and cold detection thresholds ( p < 0.01 ) at the feet correlated positively in male patients . ConclusionS mall fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity . PREP are well-suited to measure A-delta fiber conduction & NA ; The sodium channel blocker oxcarbazepine is efficacious in peripheral neuropathic pain patients , with preserved thermal sensation and some gain of sensory function , that is , the “ irritable nociceptor ” phenotype . & NA ; In neuropathic pain it has been suggested that pain phenotype based on putative pain mechanisms may predict response to treatment . This was a r and omised , double‐blind , placebo‐controlled , and phenotype‐stratified study with 2 6‐week treatment periods of oxcarbazepine ( 1800‐2400 mg ) and placebo . The primary efficacy measure was change in median pain intensity between baseline and the last week of treatment measured on an 11‐point numeric rating scale , and the primary objective was to compare the effect of oxcarbazepine in patients with and without the irritable nociceptor phenotype as defined by hypersensitivity and preserved small nerve fibre function determined by detailed quantitative sensory testing . Ninety‐seven patients with peripheral neuropathic pain due to polyneuropathy , surgical or traumatic nerve injury , or postherpetic neuralgia were r and omised . The intention‐to‐treat population comprised 83 patients : 31 with the irritable and 52 with the nonirritable nociceptor phenotype . In the total sample , oxcarbazepine relieved pain of 0.7 points ( on a numeric rating scale 0‐10 ; 95 % confidence interval [ CI ] 0.4‐1.4 ) more than placebo ( P = 0.015 ) and there was a significant interaction between treatment and phenotype of 0.7 ( 95 % CI 0.01‐1.4 , P = 0.047 ) . The number needed to treat to obtain one patient with more than 50 % pain relief was 6.9 ( 95 % CI 4.2‐22 ) in the total sample , 3.9 ( 95 % CI 2.3‐12 ) in the irritable , and 13 ( 95 % CI 5.3‐∞ ) in the nonirritable nociceptor phenotype . In conclusion , oxcarbazepine is more efficacious for relief of peripheral neuropathic pain in patients with the irritable vs the nonirritable nociceptor phenotype Summary Topical clonidine significantly reduces pain associated with diabetic neuropathy in subjects with functional nociceptors in the affected skin , as revealed by testing with topical capsaicin . Abstract A length‐dependent neuropathy with pain in the feet is a common complication of diabetes ( painful diabetic neuropathy ) . It was hypothesized that pain may arise from sensitized‐hyperactive cutaneous nociceptors , and that this abnormal signaling may be reduced by topical administration of the α2‐adrenergic agonist , clonidine , to the painful area . This was a r and omized , double‐blind , placebo‐controlled , parallel‐group , multicenter trial . Nociceptor function was measured by determining the painfulness of 0.1 % topical capsaicin applied to the pretibial area of each subject for 30 minutes during screening . Subjects were then r and omized to receive 0.1 % topical clonidine gel ( n = 89 ) or placebo gel ( n = 90 ) applied 3 times a day to their feet for 12 weeks . The difference in foot pain at week 12 in relation to baseline , rated on a 0–10 numerical pain rating scale ( NPRS ) , was compared between groups . Baseline NPRS was imputed for missing data for subjects who terminated the study early . The subjects treated with clonidine showed a trend toward decreased foot pain compared to the placebo‐treated group ( the primary endpoint ; P = 0.07 ) . In subjects who felt any level of pain to capsaicin , clonidine was superior to placebo ( P < 0.05 ) . In subjects with a capsaicin pain rating ⩾2 ( 0–10 , NPRS ) , the mean decrease in foot pain was 2.6 for active compared to 1.4 for placebo ( P = 0.01 ) . Topical clonidine gel significantly reduces the level of foot pain in painful diabetic neuropathy subjects with functional ( and possibly sensitized ) nociceptors in the affected skin as revealed by testing with topical capsaicin . Screening for cutaneous nociceptor function may help distinguish c and i date s for topical therapy for neuropathic pain This study aim ed at evaluating the performance of a battery of morphological and functional tests for the assessment of small nerve fiber loss in asymptomatic diabetic neuropathy ( DNP ) . Patients diagnosed for ≥10 years with type 1 ( n = 10 ) or type 2 ( n = 13 ) diabetes mellitus ( DM ) without conventional symptoms or signs of DNP were recruited and compared with healthy controls ( n = 18 ) and patients with overt DNP ( n = 5 ) . Intraepidermal nerve fiber density ( IENFd ) was measured with PGP9.5 immunostaining on punch skin biopsies performed at the distal leg . Functional tests consisted of quantitative sensory testing ( QST ) for light-touch , cool , warm and heat pain detection thresholds and brain-evoked potentials with electrical ( SEPs ) and CO2 laser stimulation [ laser-evoked potentials ( LEPs ) ] of h and dorsum and distal leg using small ( 0.8 mm2 ) and large ( 20 mm2 ) beam sizes . Results confirmed a state of asymptomatic DNP in DM , but only at the distal leg . Defining a critical small fiber loss as a reduction of IENFd ≤−2 z scores of healthy controls , this state prevailed in type 2 ( 30 % ) over type 1 DM ( 10 % ) patients despite similar disease duration and current glycemic control . LEPs with the small laser beam performed best in terms of sensitivity ( 91 % ) , specificity ( 83 % ) and area-under-the ROC curve ( 0.924 ) . Although this performance was not statically different from that of warm and cold detection threshold , LEPs offer an advantage over QST given that they bypass the subjective report and are therefore unbiased by perceptual factors Hepatitis C virus (HCV)-related cryoglobulinemia commonly causes disabling complications including peripheral neuropathy and neuropathic pain . In this prospect i ve clinical , neurophysiological , and skin biopsy study we aim ed at assessing clinical characteristics and risk factors of peripheral neuropathy and neuropathic pain in patients with HCV-related cryoglobulinemia . We enrolled 69 consecutive patients with HCV-related cryoglobulinemia . We diagnosed neuropathic pain with the DN4 ( Neuropathic Pain Diagnostic ) question naire , and rated the various neuropathic pains with the Neuropathic Pain Symptom Inventory ( NPSI ) . All patients underwent a st and ard nerve conduction study to assess Aβ-fiber function , laser-evoked potentials to assess Aδ-fiber function , and skin biopsy to assess C-fiber terminals . Of the 69 patients studied , 47 had a peripheral neuropathy , and 29 had neuropathic pain . Patients with peripheral neuropathy were older than those without ( P < 0.0001 ) . While peripheral neuropathy was significantly associated with the duration of HCV infection ( P < 0.01 ) , it was unrelated to the duration of cryoglobulinemia and cryocrit ( P > 0.5 ) . The severity of peripheral neuropathy significantly correlated with the duration of HCV infection ( P < 0.05 ) . Laser-evoked potential amplitudes were significantly lower in patients with than in those without neuropathic pain ( P < 0.05 ) . Conversely , no difference was found in nerve conduction study and skin biopsy findings ( P > 0.05 ) . Our findings show that peripheral neuropathy is related to age and HCV infection , rather than to cryoglobulinemia , and neuropathic pain is associated with damage to nociceptive pathways as assessed with laser-evoked potentials ; this might be useful for design ing more effective clinical interventions for these common HCV related-cryoglobulinemia complications Objectives To determine whether small nerve fiber dysfunction predicts pain in diabetic neuropathy using quantitative sensory testing of thermal thresholds . Methods Diabetic patients with or without painful neuropathy ( n=191 ) were studied . Small nerve fiber function was assessed by quantitative sensory testing of cold detection and heat pain thresholds . Subjects were also categorized as being hyperalgesic ( < 10th percentile ) or hyposensitive ( > 90th percentile ) by comparing with normative data . Vibration perception threshold , a large nerve fiber function , was measured using a biothesiometer ( Bio-medical Instrument , Newbury , OH ) . Results In the patients with pain , cold stimulus was detected after a greater reduction in temperature from baseline ( −3.7 ° C vs. −0.6 in the no-pain group , P<0.0001 ) . There were no differences between the pain and painless groups in the heat pain tests , with hyperalgesia noted in about 60 % of subjects . Vibration perception threshold and loss of ankle reflexes were significant determinants of pain , but together they accounted for only 6.8 % of the variance . If these were removed from the model , cold detection threshold became a significant determinant of pain but accounted for only 3.0 % of the variance . Conclusions Quantitative sensory testing of small nerve fiber function is a useful test to detect the presence of neuropathy , and overall diabetic patients with neuropathic pain have more sensory loss . However , small nerve fiber abnormalities detected by quantitative sensory testing do not predict the presence of pain in diabetic neuropathy We sought to determine whether early nerve damage may be detected by corneal confocal microscopy ( CCM ) , skin biopsy , and neurophysiological tests in 86 recently diagnosed type 2 diabetic patients compared with 48 control subjects . CCM analysis using novel algorithms to reconstruct nerve fiber images was performed for all fibers and major nerve fibers ( MNF ) only . Intraepidermal nerve fiber density ( IENFD ) was assessed in skin specimens . Neurophysiological measures included nerve conduction studies ( NCS ) , quantitative sensory testing ( QST ) , and cardiovascular autonomic function tests ( AFTs ) . Compared with control subjects , diabetic patients exhibited significantly reduced corneal nerve fiber length ( CNFL-MNF ) , fiber density ( CNFD-MNF ) , branch density ( CNBD-MNF ) , connecting points ( CNCP ) , IENFD , NCS , QST , and AFTs . CNFD-MNF and IENFD were reduced below the 2.5th percentile in 21 % and 14 % of the diabetic patients , respectively . However , the vast majority of patients with abnormal CNFD showed concomitantly normal IENFD and vice versa . In conclusion , CCM and skin biopsy both detect nerve fiber loss in recently diagnosed type 2 diabetes , but largely in different patients , suggesting a patchy manifestation pattern of small fiber neuropathy . Concomitant NCS impairment points to an early parallel involvement of small and large fibers , but the precise temporal sequence should be clarified in prospect i ve studies This prospect i ve observational cohort study addressed the long-term clinical effectiveness of the management of chronic neuropathic noncancer pain at 7 Canadian tertiary pain centers . Patients were treated according to st and ard guidelines and were followed at 3 , 6 , 12 , 18 , and 24 months . St and ard outcome measures for pain , mood , quality of life , and overall treatment satisfaction were administered , with the primary outcome measure design ated as the composite of 30 % reduction in average pain intensity and 1-point decrease in the mean Interference Scale Score ( 0 - 10 ) of the Brief Pain Inventory at 12 months relative to baseline . Of 789 patients recruited , mean age was 53.5 ± 14.2 years ( 55 % female ) and mean duration of pain was 4.88 ± 5.82 years . Mean average pain intensity ( 0 - 10 ) at baseline was 6.1 ± 1.9 . All st and ard outcome measures showed statistically significant improvement at 12 months relative to baseline ( P < .001 ) . However , only 23.7 % attained clinical ly significant improvement in pain and function at 12 months as the primary outcome measure . Univariable analyses showed poorer outcomes at 12-month follow-up with longer duration of pain ( P = .002 ) , greater cigarette use ( P = .01 ) , more disability compensation ( P = .001 ) , and higher opioid doses at baseline and at 12 months ( P < .02 ) . Our present treatment modalities provide significant long-term benefit in only about a quarter of patients with neuropathic pain managed at tertiary care pain clinics . Opioid therapy may not be beneficial for the long term . Perspective : Evidence -based treatment of chronic neuropathic pain provides long-term benefit in only about one-quarter of patients seen in tertiary care centers . Opioid therapy may not be beneficial Objective : To determine the validity and reliability of the total neuropathy score ( TNS ) in normal subjects and in subjects with diabetic polyneuropathy . Background : Clinical research in peripheral neuropathy requires vali date d outcome measures . Multiple outcome measures have been used in clinical trials , including symptom measures , functional scales , quantitative clinical examinations , nerve conduction studies , computerized sensory examinations , and nerve biopsy . Each of these measures has its strengths and weaknesses . In two previous studies of toxic neuropathy from chemotherapeutic agents , the authors used the TNS as the outcome measure . The TNS combines information obtained from grading of symptoms , signs , nerve conduction studies , and quantitative sensory tests , and provides a single measure to quantify neuropathy . Methods : The authors measured the inter- and intrarater reliability of the TNS and preformed a cross-sectional validation study of the TNS and its subscales with the Mayo Clinic measures of neuropathy , neuropathy symptom score ( NSS ) , and the neurologic impairment score ( NIS ) in five healthy control subjects and 30 individuals with varying severities of diabetic polyneuropathy . Results : Inter- and intrarater reliability of the TNS was excellent ( 0.966 and 0.986 respectively ) . The cross-sectional validation study showed excellent correlations among all measures of neuropathy . Conclusions : The total neuropathy score is a vali date d measure of peripheral nerve function and could be used as an end point for clinical trials of peripheral neuropathy Objective : To investigate the effects of IV lidocaine on spontaneous and evoked pain ( allodynia and hyperalgesia ) due to peripheral nerve injury ( postherpetic neuralgia or nerve trauma ) using quantitative sensory testing . Method : The authors r and omized 22 patients to receive lidocaine 5 mg/kg IV during 30 minutes or placebo in a double-blind crossover design and 16 patients subsequently received mexiletine on an open basis titrated from 400 to 1,000 mg per day ( mean 737 mg/day ) . Results : Lidocaine induced a significant decrease in ongoing pain for up to 6 hours with a peak effect 60 to 120 minutes postinjection . The drug also decreased mechanical dynamic allodynia and static ( punctate ) mechanical allodynia/hyperalgesia , but not thermal allodynia and hyperalgesia . The effects of lidocaine and mexiletine on spontaneous pain intensity were significantly higher in patients with concomitant mechanical allodynia in comparison with those without allodynia . Conclusions : These data indicate modality-specific antihyperalgesic effects of IV lidocaine in patients with peripheral nerve injury . Patients with mechanical allodynia may be good c and i date s for treatment with local anesthetic-like drugs and possibly with other sodium-channel blockers In this prospect i ve study , intraepidermal nerve fiber densities ( IENFD ) and subepidermal nerve plexus densities ( SENPD ) were quantified by immunostaining in skin punch biopsies from the distal calf in 99 patients with clinical symptoms of painful sensory neuropathy and from 37 age-matched healthy volunteers . The clinical diagnosis was based on history and abnormal thermal thresholds on quantitative sensory testing ( QST ) . In patients with neuropathy , IENFD and SENPD were reduced to about 50 % of controls . Elevated warm detection thresholds on QST correlated with IENFD but not with SENPD . Using receiver-operating characteristic ( ROC ) curve analysis of IENFD values , the diagnostic sensitivity for detecting neuropathy was 0.80 and the specificity 0.82 . For SENPD , sensitivity was 0.81 and specificity 0.88 . With ROC analysis of both IENFD and SENPD together , the diagnostic sensitivity was further improved to 0.92 . The combined examination of IENFD and SENPD is a highly sensitive and specific diagnostic tool in patients suspected to suffer from painful sensory neuropathies but with normal values on clinical neurophysiological studies Dysesthesias of the lower limbs are a common complaint of patients and may be indicative of peripheral neuropathy . Here we investigated the prevalence and type of neuropathy in patients presenting with this complaint and compared the diagnostic performance of different diagnostic modalities . Forty-two patients were recruited prospect ively and underwent a clinical examination , nerve conduction studies , quantitative sensory testing ( QST ) , and skin biopsy at the dorsum of the foot . All patients had a correlate for their dysesthesias in at least one diagnostic modality . Most patients ( > 90 % ) had signs of small fiber loss or dysfunction . In about half of all patients large fibers were also affected . Nerve conduction studies were abnormal in 23/42 patients ( 54.8 % ) . Cold or warm detection thresholds in QST were abnormal in 15/42 ( 35.7 % ) patients . Decreased intraepidermal nerve fiber density ( IENFD ) was found in 37 patients ( 88.1 % ) , including some patients with normal QST findings . Nearly all patients with pathological QST had a reduced IENFD , indicating a high positive predictive value ( 93 % ) of QST in screening for reduced IENFD as correlate for neuropathy . Therefore in all patients with lower limb dysesthesias of unknown origin , the non-invasive methods of NCS and QST should be used and potentially complemented by skin biopsy OBJECTIVE To determine whether repetitive and cumulative exposure to low-frequency pulsed electromagnetic fields ( PEMF ) targeting painful feet can reduce neuropathic pain ( NP ) , influence sleep in symptomatic diabetic peripheral neuropathy ( DPN ) , and influence nerve regeneration . DESIGN R and omized , double-blind , placebo-controlled parallel study . SETTING Sixteen academic and clinical sites in 13 states . PARTICIPANTS Subjects ( N=225 ) with DPN stage II or III were r and omly assigned to use identical devices generating PEMF or sham ( placebo ) 2 h/d to feet for 3 months . INTERVENTIONS Nerve conduction testing was performed serially . MAIN OUTCOME MEASURES Pain reduction scores using a visual analog scale ( VAS ) , the Neuropathy Pain Scale ( NPS ) , and the Patient 's Global Impression of Change ( PGIC ) . A subset of subjects underwent serial 3-mm punch skin biopsies from 3 st and ard lower limb sites for epidermal nerve fiber density ( ENFD ) quantification . RESULTS Subjects ( N=225 ) were r and omized with a dropout rate of 13.8 % . There was a trend toward reductions in DPN symptoms on the PGIC , favoring the PEMF group ( 44 % vs 31 % ; P=.04 ) . There were no significant differences between PEMF and sham groups in the NP intensity on NPS or VAS . Twenty-seven subjects completed serial biopsies . Twenty-nine percent of PEMF subjects had an increase in distal leg ENFD of at least 0.5 SDs , while none did in the sham group ( P=.04 ) . Increases in distal thigh ENFD were significantly correlated with decreases in pain scores . CONCLUSIONS PEMF at this dosimetry was noneffective in reducing NP . However neurobiological effects on ENFD , PGIC and reduced itching scores suggest future studies are indicated with higher dosimetry ( 3000 - 5000 G ) , longer duration of exposure , and larger biopsy cohort OBJECTIVES Fibromyalgia ( FM ) is one of the most common chronic pain syndromes . Various pathogenetic mechanisms have been implicated but none is proven . Our scope was to determine if Intraepidermal Nerve Fiber Density ( IENFD ) is reduced in the skin of FM patients , as observed in patients with painful small fiber sensory neuropathy ( SFSN ) . DESIGN , SETTING AND PARTICIPANTS We prospect ively studied 46 FM patients ( 5 men and 41 women ) , aged 29 to 76 ( mean : 52.5 ) years , diagnosed according to the ACR 2010 criteria , and 34 controls ( 18 women and 16 men ) aged 19 to 84 ( mean : 31.7 ) years . IENFD was measured using published guidelines and immune markers were sought immunocytochemically . In 30 FM patients , pain intensity was assessed with the Neuropathic Pain Symptom Inventory ( NPSI ) , a scale vali date d for neuropathic pain . RESULTS 15 of 46 ( 32.6 % ) FM patients had reduced IENFD [ range : 0.6 - 12.5 fibers/mm ( mean : 4.83 SD : 2.5 ) ] , compared to healthy controls [ 2.8 - 11.5 fibers/mm ( mean : 7.35 , SD : 1.85 ) ] ( p<0.0001 ) . No significant correlation was noticed between NPSI scores and IENFD . No difference in the Langerhans cells , the major Antigen Presenting Cells ( APCs ) in the epidermis , or in IL-6 staining , was noted between FM and controls . IENFD was equally reduced in a subset of FM patients who also had another autoimmune disease . CONCLUSION This is one of the largest series of FM patients demonstrating a significant reduction of IENFD in their skin biopsies . The findings indicate that in a subset of FM patients , the pain syndrome is , at least partially , of neuropathic origin . Skin biopsy may prove a useful tool and a potential biomarker in future studies of FM patients Objective : To demonstrate the relationship between epidermal nerve fiber density ( ENFD ) in the leg and the phenotype of HIV-associated distal sensory polyneuropathy ( HIV-DSP ) in a multicenter prospect i ve study ( ACTG A5117 ) . Methods : A total of 101 HIV-infected adults , with CD4 cell count < 300 cells/mm3 and who had received antiretroviral therapy ( ART ) for at least 15 consecutive weeks , underwent st and ardized clinical and electrophysiologic assessment . All 101 subjects were biopsied at the distal leg ( DL ) and 99 at the proximal thigh ( PT ) at baseline . ENFD was assessed by skin biopsy using PGP9.5 immunostaining . Associations of ENFD with demographics , ART treatment , Total Neuropathy Score ( TNS ) , sural sensory nerve action potential ( SNAP ) amplitude and conduction velocity , quantitative sensory testing ( QST ) measures , and neuropathic pain were explored . Results : ENFD at the DL site correlated with neuropathy severity as gauged by TNS ( p < 0.01 ) , the level of neuropathic pain quantified by the Gracely Pain Scale ( GPS ) ( p = 0.01 ) and Visual Analogue Scale ( VAS ) ( p = 0.01 ) , sural SNAP amplitude ( p < 0.01 ) , and toe cooling ( p < 0.01 ) and vibration ( p = 0.02 ) detection thresholds . ENFD did not correlate with neurotoxic ART exposure , CD4 cell count , or plasma HIV-1 viral load . Conclusions : In subjects with advanced HIV-1 infection , epidermal nerve fiber density ( ENFD ) assessment correlates with the clinical and electrophysiologic severity of distal sensory polyneuropathy ( DSP ) . ENFD did not correlate with previously established risk factors for HIV-DSP , including CD4 cell count , plasma HIV-1 viral load , and neurotoxic antiretroviral therapy exposure Article abstract -Despite prominent symptoms of neuropathic pain , patients with small-fiber sensory neuropathies have few objective abnormalities on clinical examination and routine electrodiagnostic studies . We quantified intraepidermal nerve fiber ( IENF ) density in sections of skin obtained by punch skin biopsy , and found it to be significantly reduced in patients with painful sensory neuropathies compared with age-matched control subjects . In addition , IENF density correlated with clinical estimates of neuropathy severity , as judged by the extent of clinical ly identifiable sensory abnormalities . IENF density at the calf was lower than that obtained from skin at more proximal sites , indicating the length dependency of small-fiber loss in these neuropathies . NEUROLOGY 1997;48 : 708 - |
1,677 | 29,237,159 | Conclusion : Recent evidence suggests that SSB consumption is positively associated with or has an effect on obesity indices in children and adults . | Objective : Partly inconsistent findings from previous review s have fueled discussion s on the impact of sugar-sweetened beverages ( SSBs ) on obesity development .
The aim was to systematic ally review the recent evidence in children and adults . | BACKGROUND It has been extensively shown , mainly in US population s , that sugar-sweetened beverages ( SSBs ) are associated with increased risk of type 2 diabetes ( T2D ) , but less is known about the effects of artificially sweetened beverages ( ASBs ) . OBJECTIVE We evaluated the association between self-reported SSB , ASB , and 100 % fruit juice consumption and T2D risk over 14 y of follow-up in the French prospect i ve Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale-European Prospect i ve Investigation into Cancer and Nutrition cohort . DESIGN A total of 66,118 women were followed from 1993 , and 1369 incident cases of T2D were diagnosed during the follow-up . Cox regression models were used to estimate HRs and 95 % CIs for T2D risk . RESULTS The average consumption of sweetened beverages in consumers was 328 and 568 mL/wk for SSBs and ASBs , respectively . Compared with nonconsumers , women in the highest quartiles of SSB and ASB consumers were at increased risk of T2D with HRs ( 95 % CIs ) of 1.34 ( 1.05 , 1.71 ) and 2.21 ( 1.56 , 3.14 ) for women who consumed > 359 and > 603 mL/wk of SSBs and ASBs , respectively . Strong positive trends in T2D risk were also observed across quartiles of consumption for both types of beverage ( P = 0.0088 and P < 0.0001 , respectively ) . In sensitivity analyses , associations were partly mediated by BMI , although there was still a strong significant independent effect . No association was observed for 100 % fruit juice consumption . CONCLUSIONS Both SSB consumption and ASB consumption were associated with increased T2D risk . We can not rule out that factors other than ASB consumption that we did not control for are responsible for the association with diabetes , and r and omized trials are required to prove a causal link between ASB consumption and T2D BACKGROUND The accumulation of abdominal fat increases risk of metabolic disorders and premature death . There is a dearth of prospect i ve data on the association between caloric beverage consumption and surrogate markers of abdominal adiposity . OBJECTIVE The aim of this study was to assess the relation between consumption of nonalcoholic caloric beverages , including soft drinks , fruit juice , whole milk , and skim and low-fat milk , and changes in waist circumference ( WC ) and odds of 10-y incidence of abdominal obesity . METHODS We conducted a prospect i ve , population -based study of 2181 Spanish men and women aged 25 - 74 y who were followed from 2000 to 2009 . We measured weight , height , and WC , and recorded data on diet and leisure-time physical activity ( LTPA ) with the use of vali date d question naires . We fit multivariable linear and logistic regression models . RESULTS A 100 kcal increase in soft drink consumption was associated with a 1.1 cm increase in WC ( P = 0.018 ) after 10 y of follow-up . Substitution of 100 kcal of soft drinks with 100 kcal of whole milk or 100 kcal of juice was associated with a 1.3 cm ( 95 % CI : 0.3 , 2.4 ) and 1.1 cm ( 95 % CI : 0.03 , 2.2 ) decrease in WC , respectively . Increasing consumption of soft drinks from baseline to follow-up led to WC gain compared with maintaining nonconsumption . Greater soft drink consumption was positively associated ( P = 0.029 ) with increased odds of 10-y incidence of abdominal obesity . CONCLUSION Adults ' consumption of soft drinks was associated with increased WC and odds of 10-y incidence of abdominal obesity . This association was moderate but consistent in all statistical models Objective To evaluate the effectiveness of a school-based intervention involving the families and teachers that aim ed to promote healthy eating habits in adolescents ; the ultimate aim of the intervention was to reduce the increase in body mass index ( BMI ) of the students . Design Paired cluster r and omized school-based trial conducted with a sample of fifth grade rs . Setting Twenty classes were r and omly assigned into either an intervention group or a control group . Participants From a total of 574 eligible students , 559 students participated in the study ( intervention : 10 classes with 277 participants ; control : 10 classes with 282 participants ) . The mean age of students was 11 years . Intervention Students attended 9 nutritional education sessions during the 2010 academic year . Parents/guardians and teachers received information on the same subjects . Main Outcome Measurement Changes in BMI and percentage of body fat . Results Intention-to-treat analysis showed that changes in BMI were not significantly different between the 2 groups ( β = 0.003 ; p = 0.75 ) . There was a major reduction in the consumption of sugar-sweetened beverages and cookies in the intervention group ; students in this group also consumed more fruits . Conclusion Encouraging the adoption of healthy eating habits promoted important changes in the adolescent diet , but this did not lead to a reduction in BMI gain . Strategies based exclusively on the quality of diet may not reduce weight gain among adolescents . Trial Registration Clinical trials.gov NCT01046474 The aim of the present study was to examine the associations of sugary drink consumption and its substitution with alternative beverages with body weight gain among young children predisposed to future weight gain . Secondary analysis of the Healthy Start Study , a 1·5-year r and omised controlled trial design ed to prevent overweight among Danish children aged 2 - 6 years ( n 366 ) , was carried out . Multivariate linear regression models were used to investigate the associations of beverage consumption with change in body weight ( Δweight ) or BMI ( Δ BMI ) z-score . Substitution models were used to extrapolate the influence of replacing sugary drinks with alternative beverages ( water , milk and diet drinks ) on Δweight or Δ BMI z-score . Sugary drink intake at baseline and substitution of sugary drinks with milk were associated with both Δweight and Δ BMI z-score . Every 100 g/d increase in sugary drink intake was associated with 0·10 kg and 0·06 unit increases in body weight ( P=0·048 ) and BMI z-score ( P=0·04 ) , respectively . Substitution of 100 g/d sugary drinks with 100 g/d milk was inversely associated with Δweight ( β=-0·16 kg ; P=0·045 ) and Δ BMI z-score ( β=-0·07 units ; P=0·04 ) . The results of this study suggest that sugary drink consumption was associated with body weight gain among young children with high predisposition for future overweight . In line with the current recommendations , sugary drinks , whether high in added or natural sugar , should be discouraged to help prevent childhood obesity . Milk may be a good alternative to sugary drinks with regard to weight management among young obesity-predisposed children OBJECTIVES To examine the relationship between diet soda ( DS ) intake ( DSI ) and long-term waist circumference ( WC ) change ( ΔWC ) in the biethnic San Antonio Longitudinal Study of Aging ( SALSA ) . DESIGN Prospect i ve cohort study . SETTING San Antonio , Texas , neighborhoods . PARTICIPANTS SALSA examined 749 Mexican-American and European-American individuals aged 65 and older at baseline ( baseline , 1992 - 96 ) ; 474 ( 79.1 % ) survivors completed follow-up 1 ( FU1 , 2000 - 01 ) , 413 ( 73.4 % ) completed FU2 ( 2001 - 03 ) , and 375 ( 71.0 % ) completed FU3 ( 2003 - 04 ) . Participants completed a mean of 2.64 follow-up intervals , for 9.4 total follow-up years . MEASUREMENTS DSI , WC , height , and weight were measured at outset and at the conclusion of each interval : baseline , FU1 , FU2 , and FU3 . RESULTS Adjusted for initial WC , demographic characteristics , physical activity , diabetes mellitus , and smoking , mean interval ΔWC of DS users ( 2.11 cm , 95 % confidence interval ( CI ) = 1.45 - 2.76 cm ) was almost triple that of nonusers ( 0.77 cm , 95 % CI = 0.29 - 1.23 cm ) ( P < .001 ) . Adjusted interval ΔWCs were 0.77 cm ( 95 % CI = 0.29 - 1.23 cm ) for nonusers , 1.76 cm ( 95 % CI = 0.96 - 2.57 cm ) for occasional users , and 3.04 cm ( 95 % CI = 1.82 - 4.26 cm ) for daily users ( P = .002 for trend ) . This translates to ΔWCs of 0.80 inches for nonusers , 1.83 inches for occasional users , and 3.16 for daily users over the total SALSA follow-up . In subanalyses stratified for selected covariates , ΔWC point estimates were consistently higher in DS users . CONCLUSION In a striking dose-response relationship , increasing DSI was associated with escalating abdominal obesity , a potential pathway for cardiometabolic risk in this aging population Objective Sales of regular soda are declining , but sales of other sweetened beverages , such as sports drinks , are increasing . Our objective was to determine the prospect i ve associations between sports drinks and body mass index ( BMI ) gains among adolescents and young adults . Design and Methods We prospect ively followed 4,121 females and 3,438 males in the Growing Up Today Study II , aged 9–16 in 2004 , from across the United States . Data was collected by question naire in 2004 , 2006 , 2008 , and 2011 . Servings per day of various beverages were assessed with a food frequency question naire . Results Among the girls , each serving per day of sports drink predicted an increase of 0.3 BMI units ( 95 % confidence interval ( CI ) CI 0.03–0.54 ) more than their peers over the next 2–3 years . Among the males , each serving of sports drinks predicted a 0.33 BMI ( 95 % CI 0.09 , 0.66 ) increase . In addition , boys who increased their intake over the 2–3 year interval gained significantly more than their peers during the same time interval . Conclusions Intake of sports drinks predicted larger increases in BMI among both females and males . Our results suggest that school policies focused on obesity prevention should be augmented to restrict sports drinks Sugar-sweetened beverages ( SSB ) contribute to excessive weight gain through added energy intake . Replacing SSB with water is one strategy that has shown promise in helping lower excessive energy intake . Using nationally representative data from US adults ( n = 19,718 ) from NHANES 2007–2012 we examine the impact of replacing SSB with water on Healthy Beverage Index ( HBI ) scores and obesity prevalence . Replacing an 8-ounce serving of SSB with water lowered the percent of energy from beverages from 17 % to 11 % ( among those consuming 1 serving SSB/day ) . Reductions in the percent energy from beverages were observed across all SSB consumption groups ( 1–2 servings/day and > 2 servings/day ) . Among adults there was a 9 % to 21 % improvement in HBI score when one serving of water replaced one serving of SSB . Using previously published r and omized controlled trials ( RCT ) and meta-analyses of measured weight loss we also predicted a reduction in the prevalence of obesity ( observed : 35.2 % ; predicted 33.5%–34.9 % , p < 0.05 ) and increase in the prevalence of normal weight ( observed : 29.7 % ; high weight loss : 31.3 % , p < 0.05 ) . Our findings provide further epidemiologic evidence that water in the place of SSB can be used as a strategy to limit energy intake and help individuals meet beverage intake recommendations Background / Objectives : This longitudinal study describes the relationship between young children ’s screen time , dietary habits and anthropometric measures . The hypothesis was that television viewing and other screen activities at baseline result in increased consumption of sugar-sweetened beverages ( SSB ) and increased BMI , BMI z-score and waist to height ratio ( WHtR ) two years later . A second hypothesis was that SSB consumption mediates the association between the screen activities and changes in the anthropometric measures .Subjects/ Methods : The study is a part of the prospect i ve cohort study IDEFICS ( “ Identification and prevention of dietary and lifestyle-induced health effects in children and infants ” ) , investigating diet , lifestyle and social determinants of obesity in 2 to 9-year-olds in eight European countries ( baseline n=16 225 , two-year follow-up ; n=11 038 ) . Anthropometry was objective ly measured , and behaviours were parent-reported . Results : The main hypothesis was supported , but the second hypothesis was not confirmed . The odds ratio of being in the highest quintile of % change in WHtR was 1.26 ( 95 % CI : 1.17–1.36 ) and in BMI 1.22 ( 95 % CI : 1.13–1.31 ) , for each hour per day watching television . The odds ratio of having increased SSB consumption was 1.19 ( 95 % CI : 1.09–1.29 ) for each hour per day watching TV . The associations for total screen time were slightly weaker . Conclusions : The results indicate substantial effects of TV viewing and other screen activities for young children , both on their consumption of sugary drinks and on an increase in BMI and central obesity . Our findings suggest that television viewing seems to have a stronger effect on food habits and anthropometry than other screen activities in this age group OBJECTIVE To examine the prospect i ve association between glycemic index , glycemic load ( GL ) of diets and intakes of carbohydrates , sugars , fiber , and the main carbohydrate containing food groups ( e.g. , soft drinks ) with changes in percent body fat , body mass index ( BMI ) , and waist circumference among adolescents . DESIGN AND METHODS Students aged 12 at baseline ( n = 856 ) were examined both in 2004 - 2005 and 2009 - 2011 . A semiquantitative food frequency question naire was administered . Anthropometric parameters were measured and defined using st and ardized protocol s. RESULTS After multivariable adjustment , in girls , each 1-SD increase in dietary GL was associated with concurrent 0.77 kg/m2 and 1.45 cm increase in BMI and waist circumference , respectively ( both P = 0.01 ) . Conversely , each 1-SD increase in dietary fiber intake was associated with a concurrent 0.44 kg/m2 decrease in mean BMI in girls ( P = 0.02 ) and 1.45 cm decrease in waist circumference in boys ( P = 0.002 ) . Girls who consumed soft drinks once or more per day versus those who never/rarely consumed soft drinks , had a 4.45 % increase in percent body fat after 5 years ( Ptrend = 0.01 ) . CONCLUSIONS High-GL foods might adversely influence development of body composition , particularly in girls , whereas fiber-rich diets could limit excess weight during adolescence Consumption of sugar-sweetened beverages has been shown , largely in American population s , to increase type 2 diabetes incidence . We aim ed to evaluate the association of consumption of sweet beverages ( juices and nectars , sugar-sweetened soft drinks and artificially sweetened soft drinks ) with type 2 diabetes incidence in European adults . We established a case – cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . After exclusions , the final sample size included 11,684 incident cases and a subcohort of 15,374 participants . Cox proportional hazards regression models ( modified for the case – cohort design ) and r and om-effects meta-analyses were used to estimate the association between sweet beverage consumption ( obtained from vali date d dietary question naires ) and type 2 diabetes incidence . In adjusted models , one 336 g ( 12 oz ) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 ( 95 % CI 1.09 , 1.38 ) and 1.52 ( 95 % CI 1.26 , 1.83 ) , respectively . After further adjustment for energy intake and BMI , the association of sugar-sweetened soft drinks with type 2 diabetes persisted ( HR 1.18 , 95 % CI 1.06 , 1.32 ) , but the association of artificially sweetened soft drinks became statistically not significant ( HR 1.11 , 95 % CI 0.95 , 1.31 ) . Juice and nectar consumption was not associated with type 2 diabetes incidence . This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults Objectives To determine the relationship between the reduction in salt intake that occurred in Engl and , and blood pressure ( BP ) , as well as mortality from stroke and ischaemic heart disease ( IHD ) . Design Analysis of the data from the Health Survey for Engl and . Setting and participants Engl and , 2003 N=9183 , 2006 N=8762 , 2008 N=8974 and 2011 N=4753 , aged ≥16 years . Outcomes BP , stroke and IHD mortality . Results From 2003 to 2011 , there was a decrease in mortality from stroke by 42 % ( p<0.001 ) and IHD by 40 % ( p<0.001 ) . In parallel , there was a fall in BP of 3.0±0.33/1.4±0.20 mm Hg ( p<0.001/p<0.001 ) , a decrease of 0.4±0.02 mmol/L ( p<0.001 ) in cholesterol , a reduction in smoking prevalence from 19 % to 14 % ( p<0.001 ) , an increase in fruit and vegetable consumption ( 0.2±0.05 portion/day , p<0.001 ) and an increase in body mass index ( BMI ; 0.5±0.09 kg/m2 , p<0.001 ) . Salt intake , as measured by 24 h urinary sodium , decreased by 1.4 g/day ( p<0.01 ) . It is likely that all of these factors ( with the exception of BMI ) , along with improvements in the treatments of BP , cholesterol and cardiovascular disease , contributed to the falls in stroke and IHD mortality . In individuals who were not on antihypertensive medication , there was a fall in BP of 2.7±0.34/1.1±0.23 mm Hg ( p<0.001/p<0.001 ) after adjusting for age , sex , ethnic group , education , household income , alcohol consumption , fruit and vegetable intake and BMI . Although salt intake was not measured in these participants , the fact that the average salt intake in a r and om sample of the population fell by 15 % during the same period suggests that the falls in BP would be largely attributable to the reduction in salt intake rather than antihypertensive medications . Conclusions The reduction in salt intake is likely to be an important contributor to the falls in BP from 2003 to 2011 in Engl and . As a result , it would have contributed substantially to the decreases in stroke and IHD mortality Aims /hypothesisThis study aim ed to evaluate the association of types of sugar-sweetened beverages ( SSB ) ( soft drinks , sweetened-milk beverages , sweetened tea/coffee ) , artificially sweetened beverages ( ASB ) and fruit juice with incident type 2 diabetes and determine the effects of substituting non-SSB for SSB and the population -attributable fraction of type 2 diabetes due to total sweet beverages . Methods Beverage consumption of 25,639 UK-resident adults without diabetes at baseline ( 1993–1997 ) in the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Norfolk study was assessed using 7-day food diaries . During 10.8 years of follow-up 847 incident type 2 diabetes cases were verified . Results In adjusted Cox regression analyses there were positive associations ( HR [ 95 % CI ] per serving/day ] ) for soft drinks 1.21 ( 1.05 , 1.39 ) , sweetened-milk beverages 1.22 ( 1.05 , 1.43 ) and ASB 1.22 ( 1.11 , 1.33 ) , but not for sweetened tea/coffee 0.98 ( 0.94 , 1.02 ) or fruit juice 1.01 ( 0.88 , 1.15 ) . Further adjustment for adiposity attenuated the association of ASB , HR 1.06 ( 0.93 , 1.20 ) . There was a positive dose – response relationship with total sweet beverages : HR per 5 % energy 1.18 ( 1.11 , 1.26 ) . Substituting ASB for any SSB did not reduce the incidence in analyses accounting for energy intake and adiposity . Substituting one serving/day of water or unsweetened tea/coffee for soft drinks and for sweetened-milk beverages reduced the incidence by 14%–25 % . If sweet beverage consumers reduced intake to below 2 % energy , 15 % of incident diabetes might be prevented . Conclusions /interpretationThe consumption of soft drinks , sweetened-milk beverages and energy from total sweet beverages was associated with higher type 2 diabetes risk independently of adiposity . Water or unsweetened tea/coffee appear to be suitable alternatives to SSB for diabetes prevention . These findings support the implementation of population -based interventions to reduce SSB consumption and increase the consumption of suitable alternatives OBJECTIVE We examined whether drinking water per se is associated with drinking less of other beverages and whether changes in BMI are associated with the intake of water and other beverages . DESIGN Secondary analysis of a r and omized trial of fourth grade rs followed over 1 year . SETTING Public schools in the metropolitan area of Rio de Janeiro , Brazil . SUBJECTS Participants were 1134 students aged 10 - 11 years . RESULTS At baseline , a higher frequency of water consumption was associated with a greater daily intake of fruit juice ( P = 0.02 ) and a higher daily frequency of milk ( P = 0.005 ) . In the intervention group , the baseline frequency of water consumption was negatively associated with weight change over 1 year but without statistical significance ( coefficient = -0.08 kg/m2 ; 95 % CI -0.37 , 0.24 kg/m2 ) , whereas fruit juice intake frequency was positively associated with weight change : each increase in fruit juice intake of 1 glass/d was associated with a BMI increase of 0.16 ( 95 % CI 0.02 , 0.30 ) kg/m2 . CONCLUSIONS Our findings do not support a protective effect of water consumption on BMI , but confirm consumption of juice drinks as a risk factor for BMI gain . Students who reported high water consumption also reported high intake of other beverages ; therefore , the promotion of water consumption per se would not prevent excessive weight gain BACKGROUND AND OBJECTIVE : Although sugar-sweetened beverage ( SSB ) consumption has been tightly linked to weight status among older children , the data regarding these relationships in children aged 2 to 5 years have been mixed . Our objective was to evaluate longitudinal and cross-sectional relationships between SSB consumption and weight status among children aged 2 to 5 years . METHODS : We assessed SSB consumption and BMI z scores among 9600 children followed in the Early Childhood Longitudinal Survey — Birth Cohort , using linear and logistic regression and adjusting for race/ethnicity , socioeconomic status , mother ’s BMI , and television viewing . RESULTS : Higher rates of SSB consumption were associated with higher BMI z scores among children age 4 ( P < .05 ) and 5 ( P < .001 ) but not yet at 2 years . Children aged 5 years who drank SSB regularly ( compared with infrequent/nondrinkers ) had a higher odds ratio for being obese ( 1.43 , confidence interval 1.10–1.85 , P < .01 ) . In prospect i ve analysis , children drinking SSB at 2 years ( compared with infrequent/nondrinkers ) had a greater subsequent increase in BMI z score over the ensuing 2 years ( P < .05 ) . CONCLUSIONS : Similar to what is seen among older children , children aged 2 to 5 years drinking SSB demonstrate both prospect i ve and cross-sectional correlations with higher BMI z score . Pediatricians and parents should discourage SSB consumption to help avoid potential unhealthy weight gain in young children . From a public health st and point , strong consideration should be made toward policy changes leading to decreases in SSB consumption among children OBJECTIVE To determine the prospect i ve relationship between changes in sugar-sweetened beverage ( SSB ) intake and central adiposity in older children . DESIGN Dietary intakes of children were obtained by 3 d food records at ages 10 and 13 years . Waist circumference ( WC ) and weight and height to determine BMI were measured at 10 and 13 years and total body fat mass ( TBFM ) at 13 years by dual-energy X-ray absorptiometry . Analyses were conducted using multivariable linear regression . Reporting errors were measured and participants were categorized as under- , plausible and over-reporters of dietary intakes . SETTING Community-based British cohort of children participating in the Avon Longitudinal Study of Parents and Children . RESULTS Among 2455 older children , increased SSB consumption from ages 10 to 13 years was associated with higher WC ( st and ardized β=0.020 , P=0.19 ) , BMI ( β=0.028 , P=0.03 ) and TBFM ( β=0.017 , P=0.20 ) at 13 years . Effects were strengthened among plausible dietary reporters ( n 1059 ) : WC ( β=0.097 , P<0.001 ) , BMI ( β=0.074 , P<0.001 ) and TBFM ( β=0.065 , P=0.003 ) . The association between change in SSB and WC was weakened , but remained statistically significant after accounting for BMI ( β=0.042 , P=0.02 ) and TBFM ( β=0.048 , P=0.01 ) . CONCLUSIONS Higher consumption of SSB from ages 10 to 13 years was associated with a larger WC at age 13 years independent of differences in total adiposity . Accounting for dietary reporting errors strengthened associations . Our findings further support recommendations to limit intakes of SSB to reduce excess weight gain in children and suggest that SSB have an additional deleterious effect on central adiposity Background — Sugar-sweetened beverages ( SSBs ) are consumed globally and contribute to adiposity . However , the worldwide impact of SSBs on burdens of adiposity-related cardiovascular diseases ( CVDs ) , cancers , and diabetes mellitus has not been assessed by nation , age , and sex . Methods and Results — We modeled global , regional , and national burdens of disease associated with SSB consumption by age/sex in 2010 . Data on SSB consumption levels were pooled from national dietary surveys worldwide . The effects of SSB intake on body mass index and diabetes mellitus , and of elevated body mass index on CVD , diabetes mellitus , and cancers were derived from large prospect i ve cohort pooling studies . Disease-specific mortality/morbidity data were obtained from Global Burden of Diseases , Injuries , and Risk Factors 2010 Study . We computed cause-specific population -attributable fractions for SSB consumption , which were multiplied by cause-specific mortality/morbidity to compute estimates of SSB-attributable death/disability . Analyses were done by country/age/sex ; uncertainties of all input data were propagated into final estimates . Worldwide , the model estimated 184 000 ( 95 % uncertainty interval , 161 000–208 000 ) deaths/y attributable to SSB consumption : 133 000 ( 126 000–139 000 ) from diabetes mellitus , 45 000 ( 26 000–61 000 ) from CVD , and 6450 ( 4300–8600 ) from cancers . Five percent of SSB-related deaths occurred in low-income , 70.9 % in middle-income , and 24.1 % in high-income countries . Proportional mortality attributable to SSBs ranged from < 1 % in Japanese > 65 years if age to 30 % in Mexicans < 45 years of age . Among the 20 most populous countries , Mexico had largest absolute ( 405 deaths/million adults ) and proportional ( 12.1 % ) deaths from SSBs . A total of 8.5 ( 2.8 , 19.2 ) million disability-adjusted life years were related to SSB intake ( 4.5 % of diabetes mellitus – related disability-adjusted life years ) . Conclusions — SSBs are a single , modifiable component of diet that can impact preventable death/disability in adults in high- , middle- , and low-income countries , indicating an urgent need for strong global prevention programs |
1,678 | 15,969,772 | The results suggest that stress management may prove to be an effective way to increase the quality of life .
For all other treatments , data are insufficient for demonstrating effectiveness . | The use of complementary and alternative medicine ( CAM ) is widespread .
Yet , little is known about the evidence supporting its use in HIV/AIDS . | OBJECTIVE We tested the effects of a 10-week group-based cognitive-behavioral stress management/expressive-supportive therapy intervention ( CBSM+ ) and a time-matched individual psychoeducational condition for 330 women with AIDS reporting moderate to poor baseline quality of life ( QOL ) . The goal of this study was to examine treatment effects on total QOL and 11 QOL domains from baseline to post-intervention follow-up . METHODS Participants were assessed at baseline , r and omized to a treatment condition ( individual psychoeducation condition n=180 , group-based CBSM+ condition n=150 ) , participated in the intervention for 10 weeks and assessed again within 4 weeks following the intervention . QOL was measured using the Medical Outcomes Study -HIV-30 . RESULTS QOL scores increased over the course of both interventions for the total QOL score and three QOL domains : cognitive functioning , health distress and overall health perceptions . While women in the CBSM+ group condition showed a significant improvement in mental health QOL from pre- to post-intervention , women in the individual condition did not change . No changes were observed for energy/fatigue , health transition , single-item overall QOL , pain , physical well-being , role functioning or social functioning in either condition . CONCLUSION Results suggest that group-based CBSM+ and individual psychoeducational interventions are effective at improving certain aspects of QOL and that group-based CBSM+ may be particularly effective at increasing QOL related to mental health in this population of women with AIDS Background Stress management interventions can reduce symptoms of distress as well as modulate certain immune system components in persons infected with human immunodeficiency virus ( HIV ) . These effects may occur in parallel with reductions in hypothalamic-pituitary-adrenal ( HPA ) axis hormones such as cortisol , which has been related in other work to a down-regulation of immune system components relevant to HIV infection . The present study tested the effects of a multimodal cognitive-behavioral stress management ( CBSM ) intervention on 24-hour urinary free cortisol levels and distressed mood in symptomatic HIV+ gay men . Methods Symptomatic HIV-infected gay men who were r and omized to either a 10-week group-based CBSM intervention or a 10-week wait-list period provided psychological responses and urine sample s pre-post intervention . Results Of the 59 participants providing matched question naire data , men assigned to CBSM ( n=40 ) showed significantly lower posttreatment levels of self-reported depressed affect , anxiety , anger , and confusion than those in the wait-list control group ( n=19 ) . Among the 47 men providing urine sample s ( 34 CBSM , 13 controls ) , those assigned to CBSM revealed significantly less cortisol output as compared to controls . At the individual level , depressed mood decreases paralleled cortisol reductions over this period across the entire sample . Conclusion A time-limited CBSM intervention reduced distress symptoms and urinary free cortisol output in symptomatic HIV+ gay men and greater reductions in some aspects of distress , especially depressed mood , paralleled greater decreases in cortisol over the intervention period . If persisting stressors and depressed mood contribute to chronic HPA axis activation in HIV-infected persons , then interventions such as CBSM , which teaches them to relax , alter cognitive appraisal s , use new coping strategies , and access social support re sources , may decrease distress and depressed mood and normalize HPA axis functioning We wished to determine the short-term safety and efficacy of a Chinese medicinal herb preparation in treating symptoms of human immunodeficiency virus ( HIV ) infection in a 12-week r and omized , double-blind , placebo-controlled clinical trial in a University-affiliated acquired immunodeficiency syndrome ( AIDS ) clinic at a public general hospital . Thirty adults with symptomatic HIV infection , no previous AIDS-defining diagnosis , and CD4 + counts of 0.200 - 0.499 x 10(9)/L ( 200 - 499/mm3 ) received 28 tablets each day of either a st and ardized oral preparation of 31 Chinese herbs or a cellulose placebo . Primary outcome measures were changes in life satisfaction , perceived health , and number and severity of symptoms . Other outcomes included adherence , and changes in weight , CD4 + count , depression , anxiety , physical and social function , and mental health . Two placebo- and no herb-treated subjects had mild adverse events ( AE ) . Subjects on both arms reported taking 94 % of prescribed tablets . No differences between treatment groups reached the p < 0.05 level . Life satisfaction improved in herb-treated [ + 0.86 , 95 % confidence interval ( CI ) : + 0.29 , + 1.43 ] but not in placebo-treated subjects ( + 0.20 , 95 % CI -0.35 , + 0.75 ) . Number of symptoms was reduced in subjects receiving herbs ( -2.2 , 95 % CI -4.1 , -0.3 ) but not in those receiving placebo ( -0.3 , 95 % CI -3.2 , + 2.7 ) . There were trends toward greater improvements among herb-treated subjects on all symptom subscales except dermatologic . Believing that one was receiving herbs was strongly associated with reporting that the treatment had helped ( p < 0.005 ) , but not with changes in life satisfaction or symptoms . There were improvements in life satisfaction and symptoms among subjects receiving the herbal therapy . Whether Chinese herbs are effective in the management of symptomatic HIV infection can be adequately addressed only by larger trials of longer duration Assigned r and omly 28 neonates born to HIV-positive mothers to a massage therapy or control group . The treatment infants were given three 15-minute massages daily for 10 days . The massaged group showed superior performance on almost every Brazelton newborn cluster score and had a greater daily weight gain at the end of the treatment period unlike the control group who showed declining performance CONTEXT Peripheral neuropathy is common in persons infected with the human immunodeficiency virus ( HIV ) but few data on symptomatic treatment are available . OBJECTIVE To evaluate the efficacy of a st and ardized acupuncture regimen ( SAR ) and amitriptyline hydrochloride for the relief of pain due to HIV-related peripheral neuropathy in HIV-infected patients . DESIGN R and omized , placebo-controlled , multicenter clinical trial . Each site enrolled patients into 1 of the following 3 options : ( 1 ) a modified double-blind 2 x 2 factorial design of SAR , amitriptyline , or the combination compared with placebo , ( 2 ) a modified double-blind design of an SAR vs control points , or ( 3 ) a double-blind design of amitriptyline vs placebo . SETTING Terry Beirn Community Programs for Clinical Research on AIDS ( HIV primary care providers ) in 10 US cities . PATIENTS Patients with HIV-associated , symptomatic , lower-extremity peripheral neuropathy . Of 250 patients enrolled , 239 were in the acupuncture comparison ( 125 in the factorial option and 114 in the SAR option vs control points option ) , and 136 patients were in the amitriptyline comparison ( 125 in the factorial option and 11 in amitriptyline option vs placebo option ) . INTERVENTIONS St and ardized acupuncture regimen vs control points , amitriptyline ( 75 mg/d ) vs placebo , or both for 14 weeks . MAIN OUTCOME MEASURE Changes in mean pain scores at 6 and 14 weeks , using a pain scale ranging from 0.0 ( no pain ) to 1.75 ( extremely intense ) , recorded daily . RESULTS Patients in all 4 groups showed reduction in mean pain scores at 6 and 14 weeks compared with baseline values . For both the acupuncture and amitriptyline comparisons , changes in pain score were not significantly different between the 2 groups . At 6 weeks , the estimated difference in pain reduction for patients in the SAR group compared with those in the control points group ( a negative value indicates a greater reduction for the " active " treatment ) was 0.01 ( 95 % confidence interval [ CI ] , -0.11 to 0.12 ; P=.88 ) and for patients in the amitriptyline group vs those in the placebo group was -0.07 ( 95 % CI , -0.22 to 0.08 ; P=.38 ) . At 14 weeks , the difference for those in the SAR group compared with those in the control points group was -0.08 ( 95 % CI , -0.21 to 0.06 ; P=.26 ) and for amitriptyline compared with placebo was 0.00 ( 95 % CI , -0.18 to 0.19 ; P=.99 ) . CONCLUSIONS In this study , neither acupuncture nor amitriptyline was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy CONTEXT Alternative medicine or complementary remedies that have not been scientifically tested are nonetheless widely used to treat chronic illnesses , particularly if curative options are limited . OBJECTIVES To assess the effectiveness of Chinese medicinal herbs in reducing symptoms and improving the quality of life of HIV-infected persons . DESIGN Prospect i ve , placebo-controlled double-blind study . SETTING University-based HIV outpatient clinic . PATIENTS 68 HIV-infected adults with CD4 cell counts < 0.5 x 10(9)/L. INTERVENTION Participants were r and omized to receive four daily doses of seven pills containing a st and ardized preparation of 35 Chinese herbs or placebo for 6 months . MAIN OUTCOME MEASURES Symptoms , HIV disease progression , HIV-1 RNA plasma viral loads , CD4 and CD8 cell counts , and scores on st and ard question naires for quality of life , depression , anxiety , and coping . RESULTS Intervention and placebo groups were equivalent at baseline regarding , respectively , previous antiretroviral therapy ( 74 % versus 79 % ) , median CD4 cell counts ( 0.20 x 10(9)/L versus 0.25 x 10(9)/L ) , and median HIV-1 plasma viral loads ( 35,612 copies/ml versus 52,027 copies/ml ) . At enrollment , none of the study subjects was seriously ill or depressed , and average coping and quality of life scores were in the normal range . In all , 53 ( 78 % ) participants completed the study . Patients taking Chinese herbs reported significantly more gastrointestinal disturbances ( 79 % versus 38 % ; p = .003 ) than those receiving placebo . No therapy-related toxicities were observed . At completion of the study , no significant differences between the intervention and placebo groups were found regarding plasma viral loads , CD4 cell counts , symptoms , and psychometric parameters . HIV-1 RNA level was unchanged at study end . Among participants who were not on concomitant antiretroviral therapy , median CD4 cell counts declined by 0.05 x 10(9)/L in both the intervention and placebo groups . CONCLUSIONS This st and ardized formulation of Chinese herbs for HIV-infected individuals did not improve quality of life , clinical manifestations , plasma virus loads , or CD4 cell counts . The data suggest that this formulation of Chinese herbs is not effective when administered in a Western medicine setting In this pilot study , 20 HIV-infected children , 6 to 12 years of age , were r and omly assigned into therapeutic touch ( TT ) and mimic TT groups . The effectiveness of TT in reducing anxiety was evaluated . The self-report measure , the A-State Anxiety subscale of the Spielberger State-Trait Anxiety Inventory For Children , was administered before and immediately after interventions . As predicted , the TT intervention result ed in lower overall mean anxiety scores , whereas the mimic TT did not . These findings provide preliminary support for the use of TT in reducing the state anxiety of children with HIV infection This study tested the effects of a 7-week individual self-management and coping skills training program on various measures of health and well-being of persons with HIV/AIDS . Forty men and women were r and omly assigned the treatment or wait-list control group . Treated participants showed significant posttreatment changes on all four major measures of mood , coping , and health attitudes . Treatment significantly improved coping strategies as measured by the use and effective measures of the Jalowiec Coping Scale and several of its subscales , including decreases in use of emotive , fatalistic , and palliative coping styles . Psychological mood was improved , as measured by the Profile of Moods Total Mood Disturbance ( POMS TMD ) score and specific subscales of the POMS , which were targeted in the intervention ( e.g. , Anger ) . Treated participants also showed significant increases on the Internal subscale of the Health Attribution Test Twenty-nine gay men ( 20 HIV+ , 9 HIV- ) received daily massages for one month . A subset of 11 of the HIV+ subjects served as a within subject control group ( one month with and without massages ) . Major immune findings for the effects of the month of massage included a significant increase in Natural Killer Cell number , Natural Killer Cell Cytotoxicity , soluble CD8 , and the cytotoxic subset of CD8 cells . There were no changes in HIV disease progression markers ( CD4 , CD4/CD8 ratio , Beta-2 microglobulin , neopterin ) . Major neuroendocrine findings , measured via 24 hour urines included a significant decrease in cortisol , and nonsignificant trends toward decrease of catecholamines . There were also significant decreases in anxiety and increases in relaxation which were significantly correlated with increases in NK cell number . Thus , there appears to be an increase in cytotoxic capacity associated with massage . Implication s for HIV+ men as those with other illnesses , particularly cancer , are discussed OBJECTIVE Changes in immunologic status were evaluated in 25 HIV-infected men r and omly assigned to a 10-week stress management intervention or a wait-list control condition . METHOD The authors monitored changes in number of transitional naive T cells ( CD4(+)CD45RA(+)CD29(+ ) ) over 6 - 12 months after the completion of the intervention . RESULTS Men receiving stress management had higher CD4(+ ) CD45RA(+)CD29(+ ) cell counts at follow-up than did the control subjects . This difference was independent of initial number of naive T cells and HIV virus load . CONCLUSIONS Stress management is associated with immunologic reconstitution in HIV-positive gay men OBJECTIVES Determine effects of massage therapy alone and in combination with exercise or stress management-biofeedback treatment on enumerative immune measures , and quality of life in moderately immunocompromised human immunodeficiency virus ( HIV ) subjects . DESIGN R and omized prospect i ve controlled trial with 42 subjects r and omly assigned to one of three treatment groups or a control group receiving st and ard care and intervention over a 12-week period . SETTING Academic medical center . SUBJECTS Forty-two ( 42 ) subjects with HIV infection ( 40 males ; 2 females ; aged 27 - 50 years ) met eligibility requirements of CD4 + lymphocyte cell count greater than 200 cells per microliter ; no present or recent signs or symptoms of acquired immunodeficiency syndrome ( AIDS ) , and were not hospitalized . INTERVENTIONS A 45-minute overall body massage once per week ; similar massage and supervised aerobic exercise 2 other days per week ; similar massage and biofeedback stress management once per week ; control receiving st and ard treatment . OUTCOME MEASURES Changes in peripheral blood levels of CD4 + lymphocytes , CD8 + lymphocytes , CD4+/CD8 + lymphocyte ratio and natural killer cells ; six dimension quality -of-life assessment . RESULTS No significant changes ( p > 0.05 ) were found in any enumerative immune measure . Significant ( p < 0.05 ) differences for quality -of-life assessment were in health care utilization and health perceptions , favoring massage and stress management compared to massage only and controls . CONCLUSIONS Massage administered once per week to HIV-infected persons does not enhance immune measures . Massage combined with stress management favorably alters health perceptions and leads to less utilization of health care re sources . This suggests that HIV-infected persons receiving massage and stress management would tend to not overutilize health care services , thus possibly reducing health care costs BACKGROUND This r and omized clinical trial compared 16-week interventions with interpersonal psychotherapy , cognitive behavioral therapy , supportive psychotherapy , and supportive psychotherapy with imipramine for human immunodeficiency virus (HIV)-positive patients with depressive symptoms . METHODS Subjects ( N = 101 ; 85 male , 16 female ) with known HIV seropositivity for at least 6 months were r and omized to 16 weeks of treatment . Inclusion criteria were 24-item Hamilton Depression Rating Scale score of 15 or higher , clinical judgment of depression , and physical health sufficient to attend outpatient sessions . Therapists were trained in manualized therapies specific for HIV-positive patients . Treatment adherence was monitored . RESULTS Subjects r and omized to interpersonal psychotherapy ( n = 24 ) and supportive psychotherapy with imipramine ( n = 26 ) had significantly greater improvement on depressive measures than those receiving supportive psychotherapy ( n = 24 ) or cognitive behavioral therapy ( n = 27 ) . Similar results appeared in the completer sub sample . CONCLUSIONS Depressive symptoms appear treatable in HIV-positive patients . Interpersonal psychotherapy may have particular advantages as a psychotherapy for patients who have experienced the significant life events of HIV infection Distal symmetrical peripheral neuropathy ( DSPN ) is a particularly distressing pain syndrome associated with human immunodeficiency virus ( HIV ) disease . Capsaicin has been found to be effective in relieving pain associated with other neuropathic pain syndromes , and is mentioned as a possible topical adjuvant analgesic for the relief of DSPN . This multicenter , controlled , r and omized , double-masked clinical trial studied patients with HIV-associated DSPN and compared measures of pain intensity , pain relief , sensory perception , quality of life , mood , and function for patients who received topical capsaicin to the corresponding measures for patients who received the vehicle only . Twenty-six subjects were enrolled in the study . At the end of 1 week , subjects receiving capsaicin tended to report higher current pain scores than did subjects receiving the vehicle ( Mann-Whitney test ; P = 0.042 ) . The dropout rate was higher for the capsaicin group ( 67 % ) than for the vehicle group ( 18 % ) ( chi 2 test of association ; P = 0.014 ) . There were no other statistically significant differences between the capsaicin and vehicle groups with respect to current pain , worst pain , pain relief , sensory perception , quality of life , mood , or function at study entry or at any time during the 4-week trial . These results suggest capsaicin is ineffective in relieving pain associated with HIV-associated DSPN To determine the quality of reporting of blinding in r and omized controlled trials ( RCTs ) , we evaluated 40 consecutive RCTs published in each of five leading journals . We noted whether authors reported the blinding status of participants , health care providers , data collectors , judicial assessors of outcomes , data analysts , and manuscript writers . Explicit reporting of blinding status occurred in < 25 % of RCTs for all groups . Eighty-three RCTs , reported as double-blind , provided eight combinations of blinded groups . In conclusion , prestigious journals do not currently report blinding status optimally . To do so , journals should ab and on the term " double blind " and explicitly report the blinding status of the groups involved in RCTs . Until such reporting occurs , clinicians will be left with uncertainty about the validity of RCTs that guide their clinical practice BACKGROUND Dietary fish oil ( FO ) has been shown to modulate the immune system . The purpose of this study was to explore the effects of FO supplementation on the production of dienoic eicosanoids and cytokines in patients with human immunodeficiency virus ( HIV ) infection . METHODS This was a r and omized , prospect i ve , double-blind study that included homosexual males with HIV infection . Patients were asked to consume voluntarily five food bars daily containing FO ( n = 10 ) or safflower oil ( SO ) ( n = 9 ) for 6 weeks . At baseline and week 6 , plasma was obtained to measure incorporation of omega-3 fatty acids . At baseline , week 3 , and week 6 , measurements were made of changes in dienoic eicosanoids and cytokines from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells ( P BMC ) or spontaneously releasing cells . RESULTS In the FO group but not the SO group , there was increased incorporation of the omega-3 fatty acid docosahexaenoic acid ( DHA ) into the phospholipids of the fatty acids of the plasma . In the FO group , there was a significant decrease ( p = .01 ) in 6-keto prostagl and in ( PG ) F1 alpha released from P BMC . There was a significant increase ( p = .01 ) in interleukin (IL)-6 released from the P BMC in the FO group between baseline and week 3 and between week 3 and week 6 . At week 6 , there was significantly more IL-6 ( p = .01 ) released from the P BMC in the FO group compared with the SO group . There was no change in CD4 cell counts by analysis of variance . CONCLUSIONS The FO-containing food bars were well tolerated and allowed incorporation of omega-3 fatty acids to occur . Despite evidence of significant metabolic effects on eicosanoid and cytokine production , widespread clinical use of FO for HIV-infected patients is not warranted without further study , particularly given the trend toward a decline in CD4 cell numbers at this dose and with this type of fish oil The effects of a 10-week group-based cognitive-behavioral stress management ( CBSM ) intervention on psychological distress and plasma free testosterone in symptomatic , HIV-seropositive men were examined . Participants were r and omized to either CBSM ( n = 42 ) or a wait-list control group ( n = 23 ) . Men in the CBSM intervention showed significant increases in testosterone , whereas control participants showed significant decreases . Those participating in CBSM had significant distress reductions , whereas controls showed no such change . Alterations in free testosterone were inversely related to changes in distress states over time , independent of any changes in cortisol . These findings demonstrate that a short-term CBSM intervention increases free testosterone levels among symptomatic , HIV-seropositive men , and alterations in free testosterone are associated with changes in psychological distress observed during CBSM OBJECTIVE This study was aim ed to evaluate the immuno-modulator role of homeopathic remedies in Human Immunodeficiency Virus ( HIV ) infection . METHODOLOGY A r and omised double blind clinical trial was conducted to compare the effect of homeopathic remedies with placebo , on CD4+ve T-lymphocytes in HIV infected individuals , conforming to Centres for Disease Control ( CDC ) stage II & III . 100 HIV+ve individuals between 18 - 50 y ( 71 % males ) were included in the study . 50 cases conformed to CDC stage II -- Asymptomatic HIV infection , and 50 cases to CDC stage III -- Persistent Generalised Lymphadenopathy ( PGL ) . Cases were stratified according to their clinical status and CD4+ve lymphocyte counts . The r and omisation charts were prepared much before the start of the trial by r and omly assigning placebo and verum codes to registration numbers from 1 to 50 . A single individualised homeopathic remedy was prescribed in each case and was followed up at intervals of 15 d to one month . A six months study was performed for each registered case . Assessment of progress was made by evaluation of CD+ve lymphocyte counts , which was the prospect ively-defined main outcome measure of the study ; the results were compared with the base line immune status . RESULTS In PGL , a statistically significant difference was observed in CD+ve T-lymphocyte counts between pre and post trial levels in verum group ( P < 0.01 ) . In the placebo group a similar comparison yielded non-significant results . ( P = 0.91 ) . Analysis of change in the pre and post trial counts of CD4+ve cells between groups was also statistically significant ( P = 0.04 ) . In asymptomatic HIV infection , differences in absolute CD4+ve lymphocyte counts between pre and post trial levels were not significant . Analysis of changes in pre and post trial CD4 levels of placebo and verum groups for combined strata of asymptomatic and PGL groups was also not significant . CONCLUSION The study suggests a possible role of homeopathic treatment in HIV infection in symptomatic phase , as evidence d by a statistically significant elevation of base line immune status in persistent generalised lymphadenopathy This study tested the effects of a 10-week group cognitive-behavioral stress management ( CBSM ) intervention on mood and immunologic parameters in HIV-seropositive gay men whose disease had progressed to a symptomatic stage . Men were r and omized to either CBSM or a modified waiting-list control group . The CBSM intervention significantly decreased self-reported dysphoria , anxiety , and total distress . Individuals who practice d relaxation more consistently had significantly greater drops in dysphoria . The intervention also decreased herpes simplex virus-Type 2 ( HSV-2 ) immunoglobulin G antibody titers . The control group showed no significant changes in either mood or antibody titers . Individual difference analyses revealed that decreases in dysphoria significantly predicted lower HSV-2 antibody titers by the end of the 10-week period . Neither group displayed changes in HSV-Type 1 antibody titers or in CD4 + or CD8 + cell numbers & NA ; The knowledge of being infected with the human immunodeficiency virus type 1 ( HIV‐1 ) brings about psychological distress and social problems including anxiety , depression , and social isolation . Participating in psychosocial intervention programs can help to reduce these problems . To date , however , very little is known about the efficacy of different intervention strategies . We implemented a study with a r and omized experimental design to investigate the effectiveness of a cognitive‐behavioral group psychotherapy ( CBT ) and an experiential group psychotherapy ( ET ) program for 39 asymptomatic HIV‐infected homosexual men . Both therapies consisted of 17 sessions over a 15‐week period . The major finding of this study was that psychosocial intervention , independent of the therapeutic orientation , decreased distress significantly , as compared with a waiting‐list control group ( WCG ) . There were no significant changes in the intervention groups as compared with the WCG in coping styles , social support , and emotional expression . Finally , CBT and ET did not differ in their effects on psychological distress or on the other psychosocial variables measured in this study HIV+ adolescents ( M CD4=466 mm3 ) recruited from a large urban university hospital 's outpatient clinic were r and omly assigned to receive massage therapy ( n = 12 ) or progressive muscle relaxation ( n = 12 ) two-times per week for 12 weeks . To assess treatment effects , participants were assessed for depression , anxiety and immune changes before and after treatment the 12 weeks treatment period . Adolescents who received massage therapy versus those who experienced relaxation therapy reported feeling less anxious and they were less depressed , and showed enhanced immune function by the end of the 12 week study . Immune changes included increased Natural Killer cell number ( CD56 ) and CD56+CD3- . In addition , the HIV disease progression markers CD4/CD8 ratio and CD4 number showed an increase for the massage therapy group only OBJECTIVE Although many studies have documented patterns of emotional distress in persons with HIV disease , there have been few controlled evaluations of therapy outcomes with these individuals . This research evaluated the effects of brief cognitive-behavioral or social support group therapy with this population . METHOD Sixty-eight depressed men with HIV infection were r and omly assigned to one of three conditions : eight-session cognitive-behavioral groups , eight-session social support groups , or a comparison condition . Before and after intervention and at 3-month follow-up , all participants were individually assessed by using measures of symptoms of distress as well as substance use and sexual practice s. RESULTS Relative to the comparison group , both the cognitive-behavioral and social support group therapies produced reductions in depression , hostility , and somatization . The social support intervention also produced reductions in overall psychiatric symptoms and tended to reduce maladaptive interpersonal sensitivity , anxiety , and frequency of unprotected receptive anal intercourse , while the cognitive-behavioral intervention result ed in less frequent illicit drug use during the follow-up period . Tests for clinical significance of change particularly underscored benefits of the social support group intervention both at postintervention and at long-term follow-up . CONCLUSIONS Brief group therapy for depressed persons with HIV infection produced reductions in symptoms of distress . The two forms of therapy result ed in shared and unique improvements in functioning , although social support groups focused on emotional coping presented greater evidence of clinical ly significant change . As more persons contract HIV infection and live longer with HIV disease , further research is needed to evaluate outcomes of mental health services with these individuals Forty-six Chinese patients with symptomatic human immunodeficiency virus ( HIV ) participated in a comparative study assessing the effectiveness of cognitive-behavioral group therapy ( CBT ) and peer support/counseling group therapy ( PSC ) in relation to improving mood and quality of life and decreasing uncertainty in illness as compared to a group receiving routine treatment with no formal psychosocial intervention . The CBT group consisted of 10 subjects , the PSC group of 10 subjects , and the comparison group of 26 subjects . There was a 24 % attrition rate . The intervention groups received 12 weekly sessions of therapy over 3 months . Assessment of mood states was carried out before r and omization ( baseline data ) , immediately postintervention ( 3-month time point ) and followed-up 3 months later ( 6-month time point ) . Assessment of quality of life and uncertainty in illness was carried out before r and omization and at the 6-month follow-up time point . Results indicated that the mood of the participants in the CBT group improved in terms of anger , tension-anxiety , depression , confusion , and overall mood . The quality of life in this group was significantly improved compared to the other two groups , as was uncertainty in illness . In the PSC group a worsening of psychologic functioning was observed immediately postintervention , but this picture dramatically improved at the follow-up assessment with improvements of up to 34 % . Quality of life also improved over time in this group by almost 5 % , but results did not reach statistical significance . This study demonstrated that psychologic interventions could decrease psychologic distress and improve quality of life in symptomatic HIV patients , indicating their use should be incorporated in the management of care of people living with HIV/AIDS We tested the impact of stress management training on sexual behavior and immune functioning in 64 gay men infected with human immunodeficiency virus ( HIV ) . Subjects r and omized to the stress management group met for eight two-hour sessions and one all day retreat to learn systematic relaxation , health behavior change , and stress management skills . Compared to those r and omized to a wait list control , treatment subjects reported significantly fewer sexual partners in the prior month at post-test ( 1.10 vs 2.29 for controls ) . There were no differences between groups in lymphocyte numbers and function STUDY OBJECTIVE To determine whether daily high-dose vitamin C alters the steady-state pharmacokinetics of indinavir , a protease inhibitor indicated for treatment of the human immunodeficiency virus type 1 . DESIGN Prospect i ve , open-label , longitudinal , two-period time series . SETTING University medical center . SUBJECTS Seven healthy volunteers . INTERVENTION Indinavir 800 mg every 8 hours was given to subjects for four doses on days 1 and 2 . Plasma sample s were then collected for indinavir pharmacokinetic determination . After a 7-day washout period , subjects were given vitamin C 1000 mg/day for 7 days . Beginning on day 6 of vitamin C administration , indinavir 800 mg every 8 hours was restarted for four doses . Plasma was then collected from subjects to determine indinavir pharmacokinetics . All subjects were given a vitamin C content-controlled diet for 1 week before the study began and throughout the study period . MEASUREMENTS AND MAIN RESULTS Steady-state plasma sample s were collected before dosing ( 0 hr ) and 0.5 , 1 , 2 , 3 , 4 , and 5 hours after dosing to determine indinavir pharmacokinetics . Parameters of interest were maximum plasma concentration ( C max ) , time to C max , area under the plasma concentration-time curve from 0 - 5 hours after the dose ( AUC 0 - 5 ) , an extrapolated 8-hour AUC ( AUC 0 - 8 ) , trough ( minimum ) plasma concentration ( C min ) , and oral clearance . Mean steady-state indinavir C max was significantly reduced ( 20 % ) after 7 days of vitamin C administration ( 10.3 + /- 1.5 vs 8.2 + /- 2.9 microg/ml , p=0.04 ) . The corresponding mean AUC 0 - 8 was also significantly decreased ( 14 % ; 26.4 + /- 7.2 vs 22.7 + /- 8.1 microg*hr/ml , p=0.05 ) . Although not statistically significant , the mean indinavir C min was 32 % lower in the presence of vitamin C ( 0.27 + /- 0.17 C vs 0.18 + /- 0.08 microg/ml , p=0.09 ) . Indinavir oral clearance and half-life were not significantly different . CONCLUSION Concomitant administration of high doses of vitamin C can reduce steady-state indinavir plasma concentrations . Subtherapeutic concentrations of antiretroviral agents have been associated with viral resistance and regimen failure , but the clinical significance of our findings remains to be established The use of complementary and alternative medicine ( CAM ) has grown dramatically in recent years , as has research on the safety and efficacy of CAM treatments . Minimal attention , however , has been devoted to the ethical issues relating to research on CAM . We argue that public health and safety dem and rigorous research evaluating CAM therapies , research on CAM should adhere to the same ethical requirements for all clinical research , and r and omized , placebo-controlled clinical trials should be used for assessing the efficacy of CAM treatments whenever feasible and ethically justifiable . In addition , we explore the legitimacy of providing CAM and conventional therapies that have been demonstrated to be effective only by virtue of the placebo effect OBJECTIVE : To examine the effect of dronabinol ( delta-9-tetrahydrocannabinol ) on appetite and nutritional status in patients with symptomatic HIV infection and weight loss . DESIGN : Double-blind , r and omized , placebo-controlled , crossover trial with two five-week treatment periods separated by a two-week washout period . Patients received dronabinol 5 mg twice daily before meals or placebo . SETTING : A university-based HIV/AIDS clinic and a large infectious disease private practice largely devoted to care of patients with HIV . PARTICIPANTS : Twelve HIV-infected patients who had had at least a 2.25-kg weight loss participated in the study . Five patients completed the protocol , and seven withdrew ( two because of drug intolerance , two because of disease progression , two because of noncompliance , and one because of experimental antiretroviral therapy ) . MAIN OUTCOME MEASURES : Main outcome measures included caloric intake , weight , percent body fat , serum prealbumin , and symptom distress . RESULTS : During dronabinol treatment , subjects experienced increased percent body fat ( one percent , p=0.04 ) ; decreased symptom distress ( p=0.04 ) ; and trends toward weight gain ( 0.5 kg , p=0.13 ) , increased prealbumin ( 29.0 mg/L , p=0.11 ) , and improved appetite score ( p=0.14 ) . CONCLUSIONS : In a selected group of HIV-infected patients with weight loss , short-term treatment with dronabinol may result in improvement in nutritional status and symptom distress The feasibility and acceptability of cognitive behavior therapy for HIV-related peripheral neuropathic pain was examined and the potential efficacy of the intervention was compared with that of supportive psychotherapy in reducing pain , pain-related interference with functioning , and distress . Sixty-one patients were r and omly assigned to receive six weekly sessions of cognitive behavior therapy or supportive psychotherapy . Thirty-three subjects completed the protocol . Both groups showed significant reductions in pain . The cognitive behavior group improved in most domains of pain-related functional interference and distress ; the supportive psychotherapy group showed fewer gains . The high dropout rate suggests that psychotherapeutic treatments for HIV-related pain may have limited feasibility and acceptability This study explored the effects of cognitive-behavioral interventions on quality of life in persons with HIV . In a r and omized , 3 x 3 block design , 69 participants were assigned to a guided imagery , progressive muscle relaxation or control group . Following brief instruction , subjects practice d their respective intervention over six weeks . Post intervention , perceived health status , but not quality of life , was significantly different across treatment groups . Findings suggested differential effects for guided imagery and progressive muscle relaxation , with larger effects for those at mid-stage disease and for low frequency users of guided imagery Objective We have previously reported decreases in dysphoria , anxiety , and total mood disturbance in symptomatic HIV seropositive gay men after a 10-week cognitive behavioral stress management ( CBSM ) group intervention . This structured intervention was design ed a ) to increase cognitive and behavioral coping skills related to managing the distress of symptomatic HIV , and b ) to increase social support among group members . Here we examine the relative contribution of changes in coping skills and social support during the intervention period to reductions in dysphoria , anxiety , and distress-related symptoms in this sample . Methods Participants were r and omized to a 10-week CBSM group intervention or to a wait-list control condition . Coping , social supports , and mood were measured before and after the intervention period . Results Members of the CBSM group ( N = 22 ) showed significant improvement in cognitive coping strategies involving positive reframing and acceptance , and in social supports involving attachment , alliances , and guidance at the end of the 10-week CBSM program compared with controls ( N = 18 ) who showed decrements in these coping abilities and no changes in social support . Improved cognitive coping , specifically acceptance of the HIV infection , was strongly related to lower dysphoria , anxiety , and total mood disturbance in both conditions . Changes in social support and in cognitive coping skills seem to mediate the effects of the experimental condition on the changes in distress noted during the intervention . Conclusions These results suggest that cognitive coping and social support factors can be modified by psychosocial interventions and may be important determinants of the changes in psychological well-being and quality of life during symptomatic HIV infection that can be achieved through this form of intervention This study evaluated the effects of a behavioral stress-management program on anxiety , mood , self-esteem , and T-cell count in a group of HIV-positive men who were asymptomatic except for T-cell counts below 400 . The program consisted of 20 biweekly sessions of progressive muscle relaxation and electromyograph biofeedback-assisted relaxation training , meditation , and hypnosis . Ten subjects were r and omly assigned to either a treatment group or a no-treatment control group , and the 2 groups were compared on pre- to posttreatment changes in the dependent measures . Analysis showed that , compared with the no-treatment group , the treatment group showed significant improvement on all the dependent measures , which was maintained at a 1-mo . follow-up . Since stress is known to compromise the immune system , these results suggest that stress management to reduce arousal of the nervous system and anxiety would be an appropriate component of a treatment regimen for HIV infection Objective Coinfection with herpes simplex virus type 2 ( HSV-2 ) is common in individuals infected with human immunodeficiency virus ( HIV ) and may have health implication s. This study examined the effect of a 10-week cognitive behavioral stress management ( CBSM ) intervention on immunoglobulin G ( IgG ) antibody titers to HSV-2 in a group of mildly symptomatic HIV-infected gay men and the degree to which these effects were mediated by psychosocial and endocrine changes during the 10-week period . Methods Sixty-two HIV+ gay men were r and omly assigned to either a 10-week CBSM intervention ( N = 41 ) or a wait-list control condition ( N = 21 ) . Anxious mood , social support , cortisol/dehydroepi and rosterone sulfate ( DHEA-S ) ratio levels , and HSV-2 IgG antibody titers were assessed at baseline and after the 10-week period . CBSM participants also recorded their stress levels before and after at-home relaxation practice . Results HSV-2 IgG titers were significantly reduced in the CBSM participants but remained unchanged in the control group after the 10-week intervention period . Increases in one type of social support , perceived receipt of guidance , during the 10 weeks was associated with and partially mediated the effect of the intervention on HSV-2 IgG. Similarly , decreases in cortisol/DHEA-S ratio levels were associated with decreases in HSV-2 IgG , and lower mean stress levels achieved after home relaxation practice were associated with greater decreases in HSV-2 IgG among CBSM participants . Conclusions These findings suggest that behavioral and psychosocial changes occurring during CBSM interventions , including relaxation , enhanced social support , and adrenal hormone reductions , may help to explain the effects of this form of stress management on immune indices such as HSV-2 antibody titers We examined the efficacy of relaxation techniques in a sample of HIV patients without AIDS in the early stages after infection , by comparing the three groups : relaxation group ( progressive muscle relaxation and modified autogenic training ) ; ordinary supportive psychotherapy group , and finally no psychiatric treatment group . Scores for anxiety , fatigue , depression and confusion , as measured by the profile of mood states ( POMS ) , were significantly lower after relaxation than before . There were no significant differences in the POMS scores ( except for anger ) among the three groups . These two results suggest that a combination of progressive muscle relaxation and modified autogenic training is a useful method , which can be easily employed in HIV patients without AIDS |
1,679 | 28,440,050 | Results support the use of collagenase for enzymatic debridement in pressure ulcers , diabetic foot ulcers and in conjunction with topical antibiotics for burns . | Enzymatic debridement with collagenase is a technique that is commonly used in clinical practice .
This systematic review examines the effect of collagenase on all kinds of wounds , compared to an alternative therapy , on wound healing , wound bed characteristics , cost-effectiveness and the occurrence of adverse events . | Background Approximately 10%–15 % of people with diabetes develop at least one foot ulcer during their lifetime . Treatment of diabetic foot ulcers ( DFUs ) represents a significant economic burden . Enzymatic debridement with clostridial collagenase ointment ( CCO ) can be used to remove necrotic tissue from wounds . This study examined the impact of CCO as an effective adjunct therapy to serial sharp debridement ( SSD ) and assessed the cost-effectiveness of CCO compared with st and ard DFU treatments over 1 year . Methods Adults 18 years or older with a diagnosis of type 1 or type 2 diabetes who had a neuropathic DFU were enrolled in a 12-week , r and omized , open-label trial . Patients were r and omly assigned to either treatment with CCO + SSD or to investigator-selected supportive care + SSD ( Control ) . A 3-state Markov model with a 1-week cycle length was developed using wound-closure rates from the trial to estimate the number of healed-wound weeks and the expected DFU cost per patient . The 3 states included unhealed , healed , and death . Results were extrapolated to 1 year to estimate the number of healed-wound weeks per treatment and the average cost to achieve epithelialization . The perspective of the analysis was that of the payer , specifically , the third party payer . Results The study sample included 55 patients ( 28 in CCO group ; 27 Control ) . The majority were men ( 74.5 % ) with a mean age of 57.9 years . Projected healing rates were greater for the CCO + SSD group compared to Control ( 89 % vs. 80 % , respectively ) . The expected number of epithelialized weeks accumulated over 1 year was 25 % greater in the CCO + SSD group than for Control ( 35 vs. 28 weeks , respectively ) . Over a 1-year time horizon , the expected cost per DFU was greater in the Control group than the CCO group ( $ 2,376 vs. $ 2,099 , respectively ) . The estimated cost per ulcer-free week was 40 % higher for Control ( $ 85/closed-wound week ) than for CCO + SSD ( $ 61/closed-wound week ) . Conclusions CCO + SSD therapy is a cost-effective method of debridement in the management of patients with DFUs , providing better outcomes at a lower cost . Further high quality trials are needed to confirm this finding . Trial registration This study was registered at Clinical Trials.gov as NCT01408277 BACKGROUND Despite significant advances , the treatment of diabetic foot ulcers ( DFUs ) remains a major therapeutic challenge for clinicians , surgeons , and other health care professionals . There is an urgent need for new strategies with clinical ly effective interventions to treat DFUs to reduce the burden of care in an efficient and cost-effective way . OBJECTIVE This r and omized trial evaluated and compared the clinical effectiveness , tolerability , and costs of clostridial collagenase ointment ( CCO ) debridement to that of debridement using saline moistened gauze ( SMG ) and selective sharp debridement for the treatment of DFUs . METHODS R and omized , controlled , parallel group , multicenter , open-label , 12-week study of 48 patients with neuropathic DFUs r and omized to 4 weeks of treatment with either CCO or SMG after baseline surgical debridement . The primary end point was the condition of the ulcer bed at the end of treatment as measured using a st and ardized wound assessment tool . Secondary end points were the percentage of reduction in wound area and therapeutic response rates . Adverse events were monitored for the tolerability analysis . In addition , a comparative cost-effectiveness analysis was performed from the perspective of the Centers for Medicare and Medicaid Services as a payer . RESULTS Both the CCO and SMG groups had significantly improved wound assessment scores after 4 weeks of treatment ( CCO , -2.5 , P = 0.007 ; SMG , -3.4 , P = 0.006 ) . Only CCO treatment result ed in a statistically significant decrease from baseline in the mean wound area at the end of treatment ( P = 0.0164 ) and at the end of follow-up ( P = 0.012 ) . In addition , the CCO group exhibited a significantly better response rate at the end of follow-up compared with the SMG group ( 0.92 vs 0.75 , P < 0.05 ) . Reported adverse events were similar between the 2 treatment groups . None of the reported adverse events were considered to be related to treatment . The economic analysis indicated that the direct mean costs per responder in the physician office setting of care were $ 832 versus $ 1042 for the CCO group versus the SMG group , whereas the direct mean costs per responder in the hospital outpatient department setting were $ 1607 versus $ 1980 . CONCLUSIONS CCO treatment provides equivalent debridement of DFUs similar to SMG while fostering better progress toward healing as measured by decreasing wound area over time and improved response rates at the end of follow-up . In addition , CCO yields a more favorable cost-effectiveness ratio in both the physician office and hospital outpatient department setting s of care . Clinical Trials.gov identifier : NCT01056198 INTRODUCTION The purpose of this study is to determine the cost-effectiveness of collagenase ointment relative to autolysis with a hydrogel dressing when debriding necrotic pressure ulcers in a long-term care setting . METHODS A Markov decision process model with 2 states ( necrotic nonviable wound bed transitioning to a granulated viable wound bed ) was developed using data derived from a prospect i ve , r and omized , 6-week , single-center trial of 27 institutionalized subjects with pressure ulcers that were ≥ 85 % necrotic nonviable tissue . Direct medical costs from the payer perspective included study treatments , wound treatment supplies , and nursing time . Clinical benefit was measured as " granulation days " and was derived from the time-dependent debridement rates of the alternative products . RESULTS The average cost per patient for 42 days of pressure ulcer care was $ 1,817 in 2012 for the collagenase group and $ 1,611 for the hydrogel group . Days spent with a granulated wound were 3.6 times higher for collagenase ( 23.4 vs 6.5 ) than with the hydrogel . The estimated cost per granulation day was > 3.2 times higher for hydrogel ( $ 249 ) vs collagenase ( $ 78 ) . CONCLUSIONS In this economic analysis based on a r and omized , controlled clinical trial , collagenase ointment result ed in a faster time to complete debridement and was more cost-effective than hydrogel autolysis for pressure ulcers in a long-term care setting . Even though collagenase ointment has a higher acquisition cost than hydrogel , the clinical benefit offsets the initial cost difference , result ing in lower cost per granulation day to the nursing home over the course of the 42-day analysis UNLABELLED The role of maintenance debridement in wound healing has been well described , yet little is known regarding comparative methods and associated outcomes with this process when using collagenase or hydrogel . OBJECTIVE Evaluation of maintenance debridement and wound closure with collagenase compared to hydrogel in institutionalized adults with pressure ulcers from time of necrotic tissue removal up to 84 days from enrollment . METHODS This second phase of a rollover evaluation enrolled only subjects who successfully completed phase 1 ( previously reported ) from time of necrotic tissue debridement . Subjects received daily dressing changes with either hydrogel or collagenase followed by a st and ard semiocclusive dressing to evaluate wound-healing parameters and wound closure from initial enrollment to day 84 . Investigators blinded to r and omization evaluated weekly wound photographs using a digital planimetry software package for wound-healing parameters . Additionally , Pressure Ulcer Scale for Healing ( PUSH ) © Tool and wound bed scores ( WBS ) were monitored . RESULTS Eleven of 13 subjects from the collagenase group entered into phase 2 , with 4 of the 14 subjects from the hydrogel group . One subject from each group was eliminated within the first week of phase 2 . All subjects ( n = 3 ) in the hydrogel group reached complete epithelialization with a mean of 32.6 days . Nine of 10 subjects in the collagenase group reached completed epithelialization with a mean of 45 days . An independent sample s t test showed no statistical significance between the 2 groups ( P = 0.121 ) in days to healing . A Fisher 's exact test performed on the primary endpoint of complete epithelialization also demonstrated no significant difference in outcomes between the groups ( P = 0.99 ) . Mean WBS at the onsetof phase 2 was 13.7 ( range 12 - 16 ) , and the PUSH Tool mean score was 1.0 ( range 0 - 3 ) . In aggregating phase 1 and phase 2 data , a difference in the closure rates at the end of the study , 69 % ( collagenase ) vs 21 % ( hydrogel ) , was statically significant ( P = 0.0213 ) using a Fisher 's exact test . CONCLUSION Facilitating maintenance debridement by either collagenase or hydrogel can be used to complete wound closure when used in conjunction with a vali date d predictive wound-healing tool that closely monitors therapy . This study showed statistical significance in favor of collagenase when evaluating closure rates from the onset of the pressure ulcer . OBJECTIVE A r and omised clinical trial ( n = 42 ) compared the effectiveness of two approaches to debriding chronic leg ulcers : TenderWet 24 , which is design ed to support the autolytic degradation process , and Iruxol N ( Santyl ) , an enzymatic treatment cl aim ed to enhance the degradation process . METHOD Patients were r and omly assigned to one of the two treatment groups for three weeks . Wounds were evaluated weekly for the amount of eschar/slough , the area of healthy granulation and the re-epithelialised area . RESULTS During days 1 - 14 slough within the groups was reduced by almost 19 % for TenderWet 24 and by 9 % for Iruxol N , followed by an increase of 26 % and 10 % respectively in granulation tissue . These effects were less accentuated during days 7 - 21 . There was a further 11 % improvement in tissue debridement for the TenderWet 24 group and a relapse ( + 9.1 % ) in the Iruxol N group . CONCLUSION Although TenderWet 24 appeared to be more efficient in a few cases , the general efficacy of the two products appeared to be almost the same as no statistically significant superiority of either product was found UNLABELLED Comparisons of collagenase to other methods of debridement , including wet to dry dressings , have been reported in the literature ; however , studies comparing collagenase to hydrogel have not been reported . OBJECTIVE Time to complete necrotic tissue debridement with collagenase compared to hydrogel in institutionalized adults with pressure ulcers . METHODS R and omization occurred after obtaining informed consent to avoid selection bias . Subjects received daily dressing changes with either hydrogel or collagenase followed by a st and ard semi-occlusive dressing to evaluate time to debridement up to Day 42 . Investigators , who were blinded to r and omization , evaluated weekly wound photographs for necrotic tissue debridement and wound healing parameters using a digital planimetry software package . Nonviable tissue was not cross-hatched in either group . RESULTS Twenty-seven nursing home residents were enrolled over a period of 1 year . According to a Student 's t test , there were no significant differences between groups for age , gender , age of wound , or percentage of nonviable tissue at the time of enrollment ( P = .03 ) . Using a Pearson Chi square analysis , the collagenase group was found to have statistical ( P = .003 ) significance in achieving full debridement by Day 42 . CONCLUSION This study showed statistical significance in favor of collagenase when used to debride nonviable tissue in pressure ulcers . Despite recommendations to cross-hatch eschar , statistical significance was still achieved when wounds were not cross-hatched , indicating clinical utility in setting s without clinician availability for the cross-hatching procedure During burn care the wounds must be repeatedly debrided of adherent and loose debris until the decision is made to surgically excise and graft the wound or to await epithelialization . Though native proteolytic enzymes in the skin or those produced by colonizing bacteria can speed eschar separation , the use of exogenous enzymes for wound debridement may accelerate wound cleaning and healing . Collagenase digests native and denatured collagen in necrotic tissue . This multicenter trial of 79 patients with partial-thickness wounds compared the efficacy of collagenase ointment applied with polymyxin B sulfate/bacitracin powder with the efficacy of st and ard topical antimicrobial therapy ( control ) in which silver sulfadiazine cream ( 1 % ) was used to debride paired burn sites . Patients selected for the study had two noncontiguous , partial-thickness , comparably sized , and anatomically similar burn wounds . Ages of patients ranged from 5 to 60 years ( mean 33 years ) . The total body surface area burned ranged from 2 % to 30 % ( mean 13.6 % ) . Mean burn sizes used for study treatment were 366 cm2 ( 26 to 2310 cm2 ) for collagenase sites and 355 cm2 ( 26 to 2394 cm2 ) for control sites . Sites on each patient were r and omly assigned to treatment with either collagenase or control . Endpoints were time to clean wound bed ( absence of retained debris ) and time to healing ( complete epithelialization ) . The sites treated with collagenase cleaned in less time ( mean 9.3 days ) than the control sites ( mean 11.6 days ) . Similarly the collagenase sites healed faster than the control sites ( mean 19 vs 22.1 days ) . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract Objective : To evaluate the efficacy and cost effectiveness of two treatments of pressure sores on the heel : a collagenase-containing ointment and a hydrocolloid dressing . Design : Study and cost data were collected prospect ively in a r and omised clinical trial in The Netherl and s by counting the re source use for each patient until wound healing occurred . Study participants : All 24 female study participants were in patients from the same hospital with grade IV pressure sores on the heel following orthopaedic surgery . Interventions : Two different treatment strategies were analysed : a collagenase-containing ointment ( Novuxol ® ) and a hydrocolloid dressing (Duoderm ® ).1Perspective : Hospital perspective . Main outcome measures and results : The average costs per patient for treatment with the hydrocolloid dressing were about 5 % higher than those with the collagenase-containing ointment . The treatment costs were similarly distributed within both groups , with 34 % for material s and 66 % for personnel . The cost-effectiveness analysis revealed that cost savings of 899 Dutch guilders ( 1998 values ) per successfully treated patient could be expected using the collagenase-containing ointment instead of the hydrocolloid dressing . In addition , wound healing was achieved , on average , within a shorter time period with the collagenase treatment ( 10 weeks ) compared with the hydrocolloid treatment ( 14 weeks ) . The robustness of the results were also tested using sensitivity analyses . These analyses served to confirm that collagenase treatment provides a better cost-effectiveness ratio than hydrocolloid treatment . Conclusions : With regard to overall costs and costs per successfully treated patient , this study showed collagenase treatment to be more cost effective than the hydrocolloid treatment in patients with grade IV pressure sores on the heel and that the amount of time needed for wound healing was shorter BACKGROUND proteolytic enzymes such as collagenase , fibrinolysin and deoxyribonuclease are used for debriding purulent or fibrinous pressure ulcers . OBJECTIVE to test the hypothesis that collagenase debrides necrotic pressure ulcers more effectively than fibrinolysin/deoxyribonuclease . METHODS we enrolled 135 elderly patients with pressure ulcers in a r and omized , prospect i ve double-blind trial . Patients were treated until complete wound debridement or for a maximum of 4 weeks with twice-daily applications of collagenase or fibrinolysin/deoxyribonuclease . The primary endpoint was percentage change in the yellow or black wound surface . Secondary endpoints were wound environment , margins , depth , pocketing , area and healing . Assessment was by two independent dermatologists who were unaware of the treatment administered and evaluated results from photographs taken at the beginning and end of treatment . RESULTS on intention-to-treat analysis , collagenase gave slightly better results with regard to the primary endpoint in the 121 assessable patients , but this difference was not statistically significant ( P=0.115 ) . Additional efficacy measures did not show any statistically significant difference between the groups . CONCLUSION there was no evidence of a difference between collagenase and fibrinolysin/deoxyribonuclease in the debridement of pressure ulcers The efficacy and tolerability of a new formulation of collagenase ointment ( Iruxol((R ) ) mono ) was determined in a placebo-controlled r and omised double-blind study . 30 patients with chronic ulcers of the lower extremities were treated with either Iruxol((R ) ) mono or placebo ointment base for a minimum of 14 days . Treatment efficacy was determined by evaluating wound debridement , granulation , epithelisation and inflammation using 5-point scales and by measuring wound size . All parameters were assessed daily for the first 2 weeks of treatment and weekly thereafter . For all efficacy parameters , Iruxol((R ) ) mono was significantly superior to placebo ( p < 0.01 ) . Differences reached statistical significance after 6 days of treatment for both debridement and inflammation , and after 4 , 5 and 8 days for granulation , epithelisation and wound size , respectively . In addition to individual parameters , an investigator 's rating of clinical global efficacy also demonstrated the superiority of Iruxol((R ) ) mono ( p < 0.001 ) . Iruxol((R ) ) mono and placebo were both well tolerated . Adverse events were minor and consisted of a burning sensation following ointment application in 3 patients in each group and erythema in a further 2 patients in each group . There were no withdrawals as a result of adverse events in either group . The relationship between adverse event and treatment was considered unlikely in all cases . In conclusion , Iruxol((R ) ) mono was significantly superior to placebo in all estimates of efficacy in wound healing . Iruxol((R ) ) mono was well tolerated with an adverse event profile similar to that of placebo OBJECTIVE The research ers sought to assess whether the widely used 1994 Cochrane Highly Sensitive Search Strategy ( HSSS ) for r and omized controlled trials ( RCTs ) in MEDLINE could be improved in terms of sensitivity , precision , or parsimony . METHODS A gold st and ard of 1,347 RCT records and a comparison group of 2,400 non-trials were r and omly selected from MEDLINE . Terms occurring in at least 1 % of RCT records were identified . Fifty percent of the RCT and comparison group records were r and omly selected , and the ability of the terms to discriminate RCTs from non-trial records was determined using logistic regression . The best performing combinations of terms were tested on the remaining records and in MEDLINE . RESULTS The best discriminating term was " Clinical Trial " ( Publication Type ) . In years where the Cochrane assessment of MEDLINE records had taken place , the strategies identified few additional unindexed records of trials . In years where Cochrane assessment has yet to take place , " R and omized Controlled Trial " ( Publication Type ) proved highly sensitive and precise . Adding six more search terms identified further , unindexed trials at reasonable levels of precision and with sensitivity almost equal to the Cochrane HSSS . CONCLUSIONS Most reports of RCTs in MEDLINE can now be identified easily using " R and omized Controlled Trial " ( Publication Type ) . More sensitive search es can be achieved by a brief strategy , the Centre for Review s and Dissemination/Cochrane Highly Sensitive Search Strategy ( 2005 revision ) Abstract . Purpose : Sacrococcygeal pilonidal sinus disease ( SPSD ) is a disease affecting young patients , which results in a long-term loss of productive power , and also tends to have high rates of morbidity since it has no ideal treatment . The main purpose of this study was to investigate the effectiveness of topical collagenase in the treatment of SPSD . Methods : In the present study , 40 patients admitted to our department were separated into two groups . Excision and marsupialization with dressing by bacterial collagenase was performed in the first group , while the treatment was excision and marsupialization without dressing by bacterial collagenase in the second group . Results : We determined that the healing in terms of the width and depth of the wound in the first week and in depth of wound in the second week was better in group 1 than in group 2 ( P = 0.040 , P = 0.020 , P = 0.048 , respectively ) . The duration of wound healing was 21.9 ± 1.3 days in group 1 , and 28.1 ± 1.3 days in group 2 ( P = 0.0001 ) . The recurrence rate in the intergluteal area , which heals by granulation and has no hair follicles , tends to decrease when a partial closure is obtained . Conclusion : We therefore recommend an excision , marsupialization , and dressing with bacterial collagenase , in cases with noncomplicated SPSD OBJECTIVE Fifty-five subjects with diabetes mellitus type 1 or 2 and a neuropathic , nonischemic foot ulcer were enrolled into this r and omized , controlled , multicenter trial design ed to examine the effects of debridement with clostridial collagenase ointment ( CCO ) used in conjunction with serial sharp debridement for a period of 6 weeks . METHODS Serial sharp debridement without adjunctive CCO was used in the control group . Various st and ard care therapies thought to support debridement by endogenous proteases were selected at the discretion of the investigators for use in the control group . The primary outcome measure of this trial was the percent change in ulcer area from baseline at the end of the debridement/treatment period ( EOT ) and at the end of an additional 6 weeks of follow-up ( EOS ) . Secondary objectives were to assess wound status at EOT and EOS using a st and ardized wound assessment tool , and to compare the average time to closure for ulcers debrided with serial sharp debridement with and without adjunctive CCO . RESULTS Wound area decreased relative to baseline for both the CCO group ( -68 % , -61 % ) and the control group ( -36 % , -46 % ) at EOT and EOS , respectively . While the inter-group differences did not reach statistical significance , wound area was significantly decreased from baseline at both EOT and EOS for the CCO ( P < 0.001 ) but not for the control group . Wound status scores ( scale range 8 to 40 ) improved for both groups during treatment ( CCO : -3.5 , control : -3.2 ) and follow-up ( CCO : -5.3 , control : -6.4 ) . No differences were observed in the number of sharp debridements ( CCO : 3.7 , control : 4.0 ) . Median time to closure for wounds that healed was 6 weeks for CCO and 8 weeks for control . On average , ulcers treated with serial sharp debridement plus adjunctive CCO decreased in size more rapidly than ulcers treated without adjunctive CCO debridement . No safety issues were identified based on a review of reported adverse events . CONCLUSION These results suggest there is more to wound debridement than meets the eye , and establish a foundation for larger , confirmatory studies BACKGROUND The 2 most commonly used topical agents for partial thickness burns are silver sulfadiazine ( SSD ) and collagenase ointment ( CO ) . Silver sulfadiazine holds antibacterial properties , and eschar separation occurs naturally . Collagenase ointment is an enzyme that cleaves denatured collagen facilitating separation but has no antibacterial properties . Currently , there are no prospect i ve comparative data in children for these 2 agents . Therefore , we conducted a prospect i ve r and omized trial . METHODS After institutional review board approval , patients were r and omized to daily debridement with SSD or CO . Primary outcome was the need for skin grafting . Patients were treated for 2 days with SSD with subsequent r and omization . Polymyxin was mixed with CO for antibacterial coverage . Debridements were performed daily for 10 days or until the burn healed . Grafting was performed after 10 days if not healed . RESULTS From January 2008 to January 2011 , 100 patients were enrolled , with no differences in patient characteristics . There were no differences in clinical course , outcome , or need for skin grafting . Wound infections occurred in 7 patients treated with CO and 1 patient treated with SSD ( P = .06 ) . Collagenase ointment was more expensive than SSD ( P < .001 ) . However , total hospital charges did not differ . CONCLUSION There are no differences in outcomes between topical SSD or CO in the management of childhood burns results |
1,680 | 23,300,515 | Dropout rates do not seem to be lower than in traditional exposure treatment .
Preliminary data suggest that VRET is as efficacious as traditional exposure treatment and can be especially useful in the treatment of patients who are resistant to traditional exposure | The use of Information and Communication Technologies , such as virtual reality , has been employed in the treatment of anxiety disorders with the goal of augmenting exposure treatment , which is already considered to be the first-line treatment for Post-traumatic Stress Disorder ( PTSD ) . | Abstract Virtual reality (VR)-based therapy has emerged as a potentially useful means to treat post-traumatic stress disorder ( PTSD ) , but r and omized studies have been lacking for Service Members from Iraq or Afghanistan . This study documents a small , r and omized , controlled trial of VR- grade d exposure therapy ( VR-GET ) versus treatment as usual ( TAU ) for PTSD in Active Duty military personnel with combat-related PTSD . Success was gauged according to whether treatment result ed in a 30 percent or greater improvement in the PTSD symptom severity as assessed by the Clinician Administered PTSD Scale ( CAPS ) after 10 weeks of treatment . Seven of 10 participants improved by 30 percent or greater while in VR-GET , whereas only 1 of the 9 returning participants in TAU showed similar improvement . This is a clinical ly and statistically significant result ( χ(2 ) = 6.74 , p < 0.01 , relative risk 3.2 ) . Participants in VR-GET improved an average of 35 points on the CAPS , whereas those in TAU averaged a 9-point improvement ( p < 0.05 ) . The results are limited by small size , lack of blinding , a single therapist , and comparison to a relatively uncontrolled usual care condition , but did show VR-GET to be a safe and effective treatment for combat-related PTSD Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field Eleven Vietnam veterans with war-related posttraumatic stress disorder ( PTSD ) were r and omly assigned to 10 sessions of either virtual reality exposure ( VRE ) therapy within a computer-generated virtual Vietnam environment or present-centered therapy ( PCT ) that avoided traumatic content and utilized a problem-solving approach . Participants were assessed at pretreatment , posttreatment , and 6 months posttreatment by an independent assessor blind to treatment condition . Nine participants completed treatment with one dropout per condition . No significant differences emerged between treatments , likely due to insufficient power . Although comparison of mean changes in PTSD symptoms for the VRE and PCT conditions yielded a moderate effect size ( d = 0.56 ) in favor of VRE at 6 months posttreatment , changes in PTSD scores were more variable , and therefore less reliable , within the VRE condition . The utility of VRE with older veterans with PTSD is discussed Numerous reports indicate that the growing incidence of posttraumatic stress disorder ( PTSD ) in returning Operation Enduring Freedom (OEF)/Operation Iraqi Freedom ( OIF ) military personnel is creating a significant health care and economic challenge . These findings have served to motivate research on how to better develop and disseminate evidence -based treatments for PTSD . Virtual reality-delivered exposure therapy for PTSD has been previously used with reports of positive outcomes . The current paper will detail the development and early results from use of the Virtual Iraq/Afghanistan exposure therapy system . The system consists of a series of customizable virtual scenarios design ed to represent relevant Middle Eastern context s for exposure therapy , including a city and desert road convoy environment . The process for gathering user-centered design feedback from returning OEF/OIF military personnel and from a system deployed in Iraq ( as was needed to iteratively evolve the system ) will be discussed , along with a brief summary of results from an open clinical trial using Virtual Iraq with 20 treatment completers , which indicated that 16 no longer met PTSD checklist-military criteria for PTSD after treatment BACKGROUND Virtual reality ( VR ) integrates real-time computer graphics , body-tracking devices , visual displays , and other sensory input devices to immerse a participant in a computer-generated virtual environment that changes in a natural way with head and body motion . VR exposure ( VRE ) is proposed as an alternative to typical imaginal exposure treatment for Vietnam combat veterans with posttraumatic stress disorder ( PTSD ) . METHOD This report presents the results of an open clinical trial using VRE to treat Vietnam combat veterans who have DSM-IV PTSD . In 8 to 16 sessions , 10 male patients were exposed to 2 virtual environments : a virtual Huey helicopter flying over a virtual Vietnam and a clearing surrounded by jungle . RESULTS Clinician-rated PTSD symptoms as measured by the Clinician Administered PTSD Scale , the primary outcome measure , at 6-month follow-up indicated an overall statistically significant reduction from baseline ( p = .0021 ) in symptoms associated with specific reported traumatic experiences . All 8 participants interviewed at the 6-month follow-up reported reductions in PTSD symptoms ranging from 15 % to 67 % . Significant decreases were seen in all 3 symptom clusters ( p < .02 ) . Patient self-reported intrusion symptoms as measured by the Impact of Event Scale were significantly lower ( p < .05 ) at 3 months than at baseline but not at 6 months , although there was a clear trend toward fewer intrusive thoughts and somewhat less avoidance . CONCLUSION Virtual reality exposure therapy holds promise for treating PTSD in Vietnam veterans Posttraumatic stress disorder ( PTSD ) and mild traumatic brain injury ( mTBI ) are signature illnesses of the Iraq and Afghanistan wars , but current diagnostic and therapeutic measures for these conditions are suboptimal . In our study , functional magnetic resonance imaging ( fMRI ) is used to try to differentiate military service members with : PTSD and mTBI , PTSD alone , mTBI alone , and neither PTSD nor mTBI . Those with PTSD are then r and omized to virtual reality exposure therapy or imaginal exposure . fMRI is repeated after treatment and along with the Clinician-Administered PTSD Scale ( CAPS ) and Clinical Global Impression ( CGI ) scores to compare with baseline . Twenty subjects have completed baseline fMRI scans , including four controls and one mTBI only ; of 15 treated for PTSD , eight completed posttreatment scans . Most subjects have been male ( 93 % ) and Caucasian ( 83 % ) , with a mean age of 34 . Significant improvements are evident on fMRI scans , and corroborated by CGI scores , but CAPS scores improvements are modest . In conclusion , CGI scores and fMRI scans indicate significant improvement in PTSD in both treatment arms , though CAPS score improvements are less robust CONTEXT In 2004 , the American Psychiatric Association 's Committee on Research on Psychiatric Treatments appointed a subcommittee to investigate the status of empirical evidence with regard to psychodynamic psychotherapy . OBJECTIVE As a part of this effort , the committee developed a rating scale design ed to assess the quality of r and omized controlled trials ( RCTs ) of psychotherapy . DATA SOURCES A 25-item RCT of Psychotherapy Quality Rating Scale was generated by expert consensus . Interrater reliability , internal consistency , and validity testing were undertaken using 7 trained raters . STUDY SELECTION A PubMed search was conducted to locate all RCTs of psychotherapies identified by their authors as being " psychodynamic " or " psychoanalytic " in origin and implementation . DATA EXTRACTION A total of 69 RCTs were independently rated by 2 raters . DATA SYNTHESIS The scale was found to have good interrater reliability ( total score intraclass correlation = 0.76 ) , internal consistency ( Cronbach alpha = .87 ) , and external validity . CONCLUSIONS This scale establishes a new st and ard for the design and execution of psychotherapy RCTs and provides a systematic empirical method for evaluating the quality of published RCTs |
1,681 | 28,854,902 | Although most studies focus on women as the main target group , multi-stakeholder participation with interventions occurring simultaneously at both community and facility level facilitated the impact on seeking skilled care at birth .
Increase in formal education for women most likely contributed positively to results . | Background The recent WHO report on health promotion interventions for maternal and newborn health recommends birth preparedness and complications readiness interventions to increase the use of skilled care at birth and to increase timely use of facility care for obstetric and newborn complications .
However , these interventions are complex and relate strongly to the context in which they are implemented .
In this article we explore factors to consider when implementing these interventions . | Background Pakistan has high maternal mortality , particularly in the rural areas . The delay in decision making to seek medical care during obstetric emergencies remains a significant factor in maternal mortality . Methods We present results from an experimental study in rural Pakistan . Village clusters were r and omly assigned to intervention and control arms ( 16 clusters each ) . In the intervention clusters , women were provided information on safe motherhood through pictorial booklets and audiocassettes ; traditional birth attendants were trained in clean delivery and recognition of obstetric and newborn complications ; and emergency transportation systems were set up . In eight of the 16 intervention clusters , husb and s also received specially design ed education material s on safe motherhood and family planning . Pre- and post-intervention surveys on selected maternal and neonatal health indicators were conducted in all 32 clusters . A district-wide survey was conducted two years after project completion to measure any residual impact of the interventions . Results Pregnant women in intervention clusters received prenatal care and prophylactic iron therapy more frequently than pregnant women in control clusters . Providing safe motherhood education to husb and s result ed in further improvement of some indicators . There was a small but significant increase in percent of hospital deliveries but no impact on the use of skilled birth attendants . Perinatal mortality reduced significantly in clusters where only wives received information and education in safe motherhood . The survey to assess residual impact showed similar results . Conclusions We conclude that providing safe motherhood education increased the probability of pregnant women having prenatal care and utilization of health services for obstetric complications Abstract s Background Skilled care during and immediately after delivery has been identified as one of the key strategies in reducing maternal mortality . However , recent estimates show that the status of skilled care during delivery remained very low in Ethiopia . Birth preparedness and complication readiness has been implemented as comprehensive strategy to fill this gap . However , its effectiveness in improving skilled care use has n’t been well studied . Objective The objective of this study was to determine the effect of birth preparedness and complication readiness on skilled care use in Southwest Ethiopia . Methods A prospect i ve follow-up study was conducted from September 2012-April 2013 in Southwest Ethiopia among r and omly selected 3472 mothers . Data were collected by using pre-tested interviewer administered question naires and analyzed by using SPSS for windows V.20.0 and STATA 13 . Mixed-effects multilevel logistic regression model was used to look at the relation between birth preparedness and complication readiness plan and skilled care use and identify other determinant factors . Results The status of skilled care use was 17.5 % ( 95 % CI : 16.2 % , 18.8 % ) . Factors affecting skilled care use existed both at the community as well as individual levels . Planning to use skilled care during pregnancy was found to increase actual use significantly ( OR = 2.24 ; 95%CI : 1.60 , 3.15 ) . Place of residence , access to basic emergency obstetric care , maternal education , husb and ’s occupation , wealth quintiles , number of pregnancy , inter-birth interval , knowledge of key danger signs during labor and ANC use were identified as factors affecting skilled care use . Conclusions The status of skilled care use was found to be low in the study area . Birth preparedness and complication readiness had significant effect on skilled care use . Socio-demographic , economic , access to health facility , maternal obstetric factors and antenatal care were identified as determinant factors for skilled care use . Design ing appropriate interventions to improve information , education and communication , antenatal care use , family planning and knowledge of key danger signs are recommended OBJECTIVES To determine the effectiveness of birth plans in increasing use of skilled care at delivery and in the postnatal period among antenatal care ( ANC ) attendees in a rural district with low occupancy of health units for delivery but high antenatal care uptake in northern Tanzania . METHODS Cluster r and omised trial in Ngorongoro district , Arusha region , involving 16 health units ( 8 per arm ) . Nine hundred and five pregnant women at 24 weeks of gestation and above ( 404 in the intervention arm ) were recruited and followed up to at least 1 month postpartum . RESULTS Skilled delivery care uptake was 16.8 % higher in the intervention units than in the control [ 95 % CI 2.6 - 31.0 ; P = 0.02 ] . Postnatal care utilisation in the first month of delivery was higher ( difference in proportions : 30.0 % [ 95 % CI 1.3 - 47.7 ; P < 0.01 ] ) and also initiated earlier ( mean duration 6.6 ± 1.7 days vs. 20.9 ± 4.4 days , P < 0.01 ) in the intervention than in the control arm . Women 's and providers ' reports of care satisfaction ( received or provided ) did not differ greatly between the two arms of the study ( difference in proportion : 12.1 % [ 95 % CI -6.3 - 30.5 ] P = 0.17 and 6.9 % [ 95 % CI -3.2 - 17.1 ] P = 0.15 , respectively ) . CONCLUSION Implementation of birth plans during ANC can increase the uptake of skilled delivery and post delivery care in the study district without negatively affecting women 's and providers ' satisfaction with available ANC services . Birth plans should be considered along with the range of other recommended interventions as a strategy to improve the uptake of maternal health services Background To evaluate a delivery strategy for newborn interventions in rural Bangladesh . Methods A cluster-r and omized controlled trial was conducted in Mirzapur , Bangladesh . Twelve unions were r and omized to intervention or comparison arm . All women of reproductive age were eligible to participate . In the intervention arm , community health workers identified pregnant women ; made two antenatal home visits to promote birth and newborn care preparedness ; made four postnatal home visits to negotiate preventive care practice s and to assess newborns for illness ; and referred sick neonates to a hospital and facilitated compliance . Primary outcome measures were antenatal and immediate newborn care behaviours , knowledge of danger signs , care seeking for neonatal complications , and neonatal mortality . Findings A total of 4616 and 5241 live births were recorded from 9987 and 11153 participants in the intervention and comparison arm , respectively . High coverage of antenatal ( 91 % visited twice ) and postnatal ( 69 % visited on days 0 or 1 ) home visitations was achieved . Indicators of care practice s and knowledge of maternal and neonatal danger signs improved . Adjusted mortality hazard ratio in the intervention arm , compared to the comparison arm , was 1.02 ( 95 % CI : 0.80–1.30 ) at baseline and 0.87 ( 95 % CI : 0.68–1.12 ) at endline . Primary causes of death were birth asphyxia ( 49 % ) and prematurity ( 26 % ) . No adverse events associated with interventions were reported . Conclusion Lack of evidence for mortality impact despite high program coverage and quality assurance of implementation , and improvements in targeted newborn care practice s suggests the intervention did not adequately address risk factors for mortality . The level and cause-structure of neonatal mortality in the local population must be considered in developing interventions . Programs must ensure skilled care during childbirth , including management of birth asphyxia and prematurity , and curative postnatal care during the first two days of life , in addition to essential newborn care and infection prevention and management . Trial Registration Clinical trials.gov Background Fetal and neonatal mortality rates in low-income countries are at least 10-fold greater than in high-income countries . These differences have been related to poor access to and poor quality of obstetric and neonatal care . Methods This trial tested the hypothesis that teams of health care providers , administrators and local residents can address the problem of limited access to quality obstetric and neonatal care and lead to a reduction in perinatal mortality in intervention compared to control locations . In seven geographic areas in five low-income and one middle-income country , most with high perinatal mortality rates and substantial numbers of home deliveries , we performed a cluster r and omized non-masked trial of a package of interventions that included community mobilization focusing on birth planning and hospital transport , community birth attendant training in problem recognition , and facility staff training in the management of obstetric and neonatal emergencies . The primary outcome was perinatal mortality at ≥28 weeks gestation or birth weight ≥1000 g. Results Despite extensive effort in all sites in each of the three intervention areas , no differences emerged in the primary or any secondary outcome between the intervention and control clusters . In both groups , the mean perinatal mortality was 40.1/1,000 births ( P = 0.9996 ) . Neither were there differences between the two groups in outcomes in the last six months of the project , in the year following intervention cessation , nor in the clusters that best implemented the intervention . Conclusions This cluster r and omized comprehensive , large-scale , multi-sector intervention did not result in detectable impact on the proposed outcomes . While this does not negate the importance of these interventions , we expect that achieving improvement in pregnancy outcomes in these setting s will require substantially more obstetric and neonatal care infrastructure than was available at the sites during this trial , and without them provider training and community mobilization will not be sufficient . Our results highlight the critical importance of evaluating outcomes in r and omized trials , as interventions that should be effective may not be . Trial registration Clinical Trials.gov Background Antenatal care provides an important opportunity to improve maternal underst and ing of care during and after pregnancy . Yet , studies suggest that communication is often insufficient . This research examined the effect of a job aids-focused intervention on quality of counseling and maternal underst and ing of care for mothers and newborns . Methods Counseling job aids were developed to support provider communication to pregnant women . Fourteen health facilities were r and omized to control or intervention , where providers were trained to use job aids and provided implementation support . Direct observation of antenatal counseling sessions and patient exit interviews were undertaken to assess quality of counseling and maternal knowledge . Providers were also interviewed regarding their perceptions of the tools . Data were collected before and after the job aids intervention and analyzed using a difference-in-differences analysis to quantify relative changes over time . Results Mean percent of recommended messages provided to pregnant women significantly improved in the intervention arm as compared to the control arm in birth preparedness ( difference-in-differences [ ΔI-C ] = + 17.9 , 95%CI : 6.7,29.1 ) , danger sign recognition ( ΔI-C = + 26.0 , 95%CI : 14.6,37.4 ) , clean delivery ( ΔI-C = + 21.7 , 95%CI : 10.9,32.6 ) , and newborn care ( ΔI-C = + 26.2 , 95%CI : 13.5,38.9 ) . Significant gains were also observed in the mean percent of communication techniques applied ( ΔI-C = + 28.8 , 95%CI : 22.5,35.2 ) and duration ( minutes ) of antenatal consultations ( ΔI-C = + 5.9 , 95%CI : 3.0,8.8 ) . No relative increase was found for messages relating to general prenatal care ( ΔI-C = + 8.2 , 95%CI : -2.6,19.1 ) . The proportion of pregnant women with correct knowledge also significantly improved for birth preparedness ( ΔI-C = + 23.6 , 95%CI : 9.8,37.4 ) , danger sign recognition ( ΔI-C = + 28.7 , 95%CI : 14.2,43.2 ) , and clean delivery ( ΔI-C = + 31.1 , 95%CI : 19.4,42.9 ) . There were no significant changes in maternal knowledge of general prenatal ( ΔI-C = -6.4 , 95%CI : -21.3,8.5 ) or newborn care ( ΔI-C = + 12.7 , 95%CI : -6.1,31.5 ) . Job aids were positively perceived by providers and pregnant women , although time constraints remained for health workers with other clinical responsibilities . Conclusions This study demonstrates that a job aids-focused intervention can be integrated into routine antenatal care with positive outcomes on provider communication and maternal knowledge . Efforts are needed to address time constraints and other communication barriers , including introduction of on-going quality assessment for long-term sustainability BACKGROUND In rural India , most births take place in the home , where high-risk care practice s are common . We developed an intervention of behaviour change management , with a focus on prevention of hypothermia , aim ed at modifying practice s and reducing neonatal mortality . METHODS We did a cluster-r and omised controlled efficacy trial in Shivgarh , a rural area in Uttar Pradesh . 39 village administrative units ( population 104,123 ) were allocated to one of three groups : a control group , which received the usual services of governmental and non-governmental organisations in the area ; an intervention group , which received a preventive package of interventions for essential newborn care ( birth preparedness , clean delivery and cord care , thermal care [ including skin-to-skin care ] , breastfeeding promotion , and danger sign recognition ) ; or another intervention group , which received the package of essential newborn care plus use of a liquid crystal hypothermia indicator ( ThermoSpot ) . In the intervention clusters , community health workers delivered the packages via collective meetings and two antenatal and two postnatal household visitations . Outcome measures included changes in newborn-care practice s and neonatal mortality rate compared with the control group . Analysis was by intention to treat . This study is registered as International St and ard R and omised Control Trial , number NCT00198653 . FINDINGS Improvements in birth preparedness , hygienic delivery , thermal care ( including skin-to-skin care ) , umbilical cord care , skin care , and breastfeeding were seen in intervention arms . There was little change in care-seeking . Compared with controls , neonatal mortality rate was reduced by 54 % in the essential newborn-care intervention ( rate ratio 0.46 [ 95 % CI 0.35 - 0.60 ] , p<0.0001 ) and by 52 % in the essential newborn care plus ThermoSpot arm ( 0.48 [ 95 % CI 0.35 - 0.66 ] , p<0.0001 ) . INTERPRETATION A socioculturally context ualised , community-based intervention , targeted at high-risk newborn-care practice s , can lead to substantial behavioural modification and reduction in neonatal mortality . This approach can be applied to behaviour change along the continuum of care , harmonise vertical interventions , and build community capacity for sustained development . FUNDING USAID and Save the Children-US through a grant from the Bill & Melinda Gates Foundation Introduction Birth preparedness and complication readiness have been considered as comprehensive strategy aim ed at promoting the timely utilization of skilled maternal health care . However , its status and affecting factors have not been well studied at different levels in the study area . Thus , this study was aim ed to fill this gap by conducting community based study . Methods A cross-sectional study was conducted among r and omly selected 3612 pregnant women from June-September 2012 . The data were collected by interviewer-administered structured question naire and analyzed by SPSS V.20.0 and STATA 13 . Mixed-effects multilevel logistic regression model was used to identify factors affecting birth preparedness and complication readiness . Results The status of birth preparedness and complication readiness was 23.3 % ( 95 % CI : 21.8 % , 24.9 % ) . Being in urban residence and having health center within two hours distance were among the higher level factors increasing birth preparedness and complication readiness . Educational status of primary or above , husb and 's occupation of employed or merchant , third or above wealth quintiles , knowledge of key danger signs during labor , attitude and frequency of antenatal care visits were among the lower level factors found to increase the likelihood of preparation for birth and its complications . Conclusion The status of birth preparedness and complication readiness was low in the study area . Both community level and individual level factors had important program implication s. Socio demographic , economic , knowledge of key danger signs , attitude and antenatal care use were identified as associated factors . Improving antenatal care , giving special emphasis to danger signs and community based health education are recommended Observational studies suggest that including men in reproductive health interventions can enhance positive health outcomes . A r and omized controlled trial was design ed to test the impact of involving male partners in antenatal health education on maternal health care utilization and birth preparedness in urban Nepal . In total , 442 women seeking antenatal services during second trimester of pregnancy were r and omized into three groups : women who received education with their husb and s , women who received education alone and women who received no education . The education intervention consisted of two 35-min health education sessions . Women were followed until after delivery . Women who received education with husb and s were more likely to attend a post-partum visit than women who received education alone [ RR = 1.25 , 95 % CI = ( 1.01 , 1.54 ) ] or no education [ RR = 1.29 , 95 % CI = ( 1.04 , 1.60 ) ] . Women who received education with their husb and s were also nearly twice as likely as control group women to report making > 3 birth preparations [ RR = 1.99 , 95 % CI = ( 1.10 , 3.59 ) ] . Study groups were similar with respect to attending the recommended number of antenatal care checkups , delivering in a health institution or having a skilled provider at birth . These data provide evidence that educating pregnant women and their male partners yields a greater net impact on maternal health behaviors compared with educating women alone OBJECTIVE To assess the effect on maternal health outcomes of a community-based behavior change management intervention for essential newborn care leading to a reduction in neonatal mortality . METHODS A cluster-r and omized controlled trial involving 1 control and 2 intervention arms was conducted in Shivgarh , India , between January 2004 and May 2005 . Risk-enhancing domiciliary newborn care behaviors , including those posing a concomitant risk to maternal health , were targeted through home visits and community meetings . Secondary outcomes included knowledge of maternal danger signs , self-reported complications , maternal care practice s , care-seeking from trained providers , and maternal mortality ratio ( MMR ) . The intervention arms were combined for analysis , which was done by intention to treat . RESULTS Significant improvements were observed in maternal health equity and outcomes including knowledge of danger signs , care practice s , self-reported complications , and timely care-seeking from trained providers . The difference in adjusted MMR was not significant ( relative risk 0.44 ; 95 % confidence interval , 0.14 - 1.43 ; P=0.11 ) owing to the inadequate sample size for this outcome , but may suggest a decline in MMR given improvements in other outcomes in the causal pathway to mortality . CONCLUSION Community-based strategies focused on prevention and care-seeking effectively complemented facility-based strategies toward improving maternal health , while synergizing with newborn care interventions OBJECTIVE to assess birth preparedness in expectant mothers and to evaluate its association with skilled attendance at birth in central Nepal . DESIGN a community-based prospect i ve cohort study using structured question naires . SETTING Kaski district of Nepal . PARTICIPANTS a total of 701 pregnant women of more than 5 months gestation were recruited and interviewed , followed by a second interview within 45 days of delivery . MEASUREMENTS outcome was skilled attendance at birth . Birth preparedness was measured by five indicators : identification of delivery place , identification of transport , identification of blood donor , money saving and antenatal care check-up . FINDINGS level of birth preparedness was high with 65 % of the women reported preparing for at least 4 of the 5 arrangements . It appears that the more arrangements made , the more likely were the women to have skilled attendance at birth ( OR=1.51 , p<0.001 ) . For those pregnant women who intended to save money , identified a delivery place or identified a potential blood donor , their likelihood of actual delivery at a health facility increased by two to three fold . However , making arrangements for transportation and antenatal care check-up were not significantly associated with skilled attendance at birth . CONCLUSIONS intention to deliver in a health-care facility as measured by birth preparedness indicators was associated with actual skilled attendance at birth . Birth preparedness packages could increase the proportion of skilled attendance at birth in the pathway of meeting the Millennium Development Goal 5 |
1,682 | 23,152,204 | AUTHORS ' CONCLUSIONS The continuous suturing techniques for perineal closure , compared with interrupted methods , are associated with less short-term pain , need for analgesia and suture removal . | BACKGROUND Millions of women worldwide undergo perineal suturing after childbirth and the type of repair may have an impact on pain and healing .
For more than 70 years , research ers have been suggesting that continuous non-locking suture techniques for repair of the vagina , perineal muscles and skin are associated with less perineal pain than traditional interrupted methods .
OBJECTIVES To assess the effects of continuous versus interrupted absorbable sutures for repair of episiotomy and second-degree perineal tears following childbirth . | AIMS The study aim ed to highlight any differences between the sequelae of episiorrhaphy performed using the Blair-Donatti and Guilmen-Pontonnier techniques . METHODS A total of 202 pregnant women were recruited in the Obstetrics Ward of Codogno Civic Hospital in 1994 and 1995 . Subjects were r and omly divided into two groups matched for socioeconomic status , age and parity ( group A : Guilmen-Pontonnier suture , group B : Blair-Donatti suture ) . The following parameters were evaluated : pain twenty-four hours , sixty-six hours and one , two and three months after labour , pain during sexual relations , the onset of infection , hematoma , dehiscence of the wound , and lastly the cosmetic results . RESULTS No significant differences were found between the parameters examined in both groups , barring the improved cosmetic result in group Episiotomy is a very common operation but little is known of its short-term or long-term morbidity . A prospect i ve study was design ed to record postpartum perineal discomfort and to investigate the presence and persistence of dyspareunia following episiotomy in 140 primigravidae . A comparison was made between those whose perineal skin was sutured with a subcuticular polyglycolic acid ( ; Dexon ' ) stitch and those sutured with interrupted black silk stitches . Patients sutured with subcuticular ; Dexon ' had significantly less perineal discomfort on the third , fourth , and fifth postpartum days . Patients who had epidural analgesia in labour had significantly more pain during the first five postpartum days irrespective of the suture material used . The timing of first coitus after delivery did not influence the presence or persistence of dyspareunia . Dyspareunia was commoner and lasted longer in patients sutured with ; Dexon ' and it was also commoner in older primigravidae irrespective of the suture technique BACKGROUND Trauma to the perineum is a serious and frequent problem after childbirth , with about 350000 women each year in the UK needing sutures for perineal injury after spontaneous vaginal delivery , and many millions more worldwide . We compared the continuous technique of perineal repair with the interrupted method , and the more rapidly absorbed polyglactin 910 suture material with the st and ard polyglactin 910 material . METHODS 1542 women who had a spontaneous vaginal delivery with a second-degree perineal tear or episiotomy were r and omly allocated to either the continuous ( n=771 ) or interrupted ( 771 ) suturing method , and to either the more rapidly absorbed polyglactin 910 suture material ( 772 ) or st and ard polyglactin 910 material ( 770 ) . Primary outcomes were pain 10 days after delivery and superficial dyspareunia 3 months postpartum . Analysis was by intention to treat . FINDINGS At day 10 , three women had dropped out of the study . Significantly fewer women reported pain at 10 days with the continuous technique than with the interrupted method ( 204/770 [ 26.5 % ] vs 338/769 [ 44.0 % ] , odds ratio 0.47 , 95 % CI 0.38 - 0.58 , p<0.0001 ) . Occurrence of pain did not differ significantly between groups assigned the more rapidly absorbed material or st and ard material ( 256/769 [ 33.3 % ] vs 286/770 [ 37.1 % ] , 0.84 , 0.68 - 1.04 , p=0.10 ) . Women reported no difference in superficial dyspareunia at 3 months for the continuous vs the interrupted method ( 98/581 [ 16.9 % ] vs 102/593 [ 17.2 % ] , 0.98 , 0.72 - 1.33 , p=0.88 ) or the more rapidly absorbed versus st and ard material ( 105/586 [ 17.9 % ] vs 95/588 [ 16.2 % ] , 1.13 , 0.84 - 1.54 , p=0.42 ) . Suture removal was done less with the more rapidly absorbed material than with st and ard suture material ( 22/769 [ 3 % ] vs 98/770 [ 13 % ] , p<0.0001 ) , and with the continuous versus interrupted method ( 24/770 [ 3 % ] vs 96/769 [ 12 % ] , p<0.0001 ) . INTERPRETATION A simple and widely practicable continuous repair technique can prevent one woman in six from having pain at 10 days . Also , the more rapidly absorbed polyglactin 910 material obviates need for suture removal up to 3 months postpartum for one in ten women sutured Purpose To compare different repair techniques and different suture material s for episiotomy . Methods 160 women having vertex delivery with right-mediolateral episiotomy were r and omly allocated to four groups . In the groups where continuos technique was performed , vaginal mucosa , perineal muscles and the skin were sutured continuously . In the groups of interrupted technique , vaginal mucosa was sutured with continuous sutures , then muscle layers and skin were closed by interrupted sutures . Two different types of synthetic absorbed suture material were used : monofilament type is in form of polyglycolide-co-caprolactone and multifilament one is polyglactin 910-Rapide . Perineal pain during different activities on the first and tenth day postpartum and also during sexual intercourse 6 weeks after the delivery was question ed by visual analogous scale ( VAS ) . Furthermore , repair time , amount of suture and episiotomy complications were investigated in each groups . Results On the first day after delivery , the perineal pain scores , the repair time , the amount of suture were statistically less in the continuous technique groups . The differences between the pain at tenth day and during sexual intercourse 6 weeks after the delivery were statistically same . Conclusions The continuous suturing techniques for episiotomy closure , compared to interrupted methods , are associated with less short-term pain , are quicker and also need less suture material Objective To assess the long term implication s of four alternative approaches to postpartum perineal repair . Objective To compare the effect of two methods of perineal management used during spontaneous vaginal delivery on the prevalence of perineal pain reported at 10 days after birth The aim was to compare healing and perineal pain with the use of continuous and interrupted suture techniques in women after normal delivery . A r and omized controlled trial was carried out at a hospital birth center in Itapecirica da Serra , Sao Paulo , Brazil . A total of 61 women participated with episiotomy or second degree perineal tear , allocated in two groups according to the continuous ( n=31 ) or interrupted ( n=30 ) suture techniques . The main outcomes evaluated were edema , ecchymosis , hyperemia , secretion , dehiscence , fibrosis , frequency and degree of pain ( evaluated by numerical scale from 1 to 10 ) . Data were collected during hospitalization and after discharge ( four and 41 days after birth ) . Healing occurred by first intention in 100 % of cases in both suture techniques . There were no statistically significant differences for the occurrence of morbidities , except for perineal pain due to palpation at four days after delivery , which was more frequent among women with interrupted suture OBJECTIVE Our purpose was to compare consequences for women of receiving versus not receiving median episiotomy early and 3 months post partum on the outcomes perineal pain , urinary and pelvic floor functioning by electromyography , and sexual functioning and to analyze the relationship between episiotomy and third- and fourth-degree tears . STUDY DESIGN A secondary cohort analysis was performed of participants within a r and omized clinical trial , analyzed by type of perineal trauma and pain , pelvic floor , and sexual consequences of such trauma , while controlling for trial arm . The study was conducted in three university or community hospitals ; 356 primiparous and 341 multiparous women were studied . RESULTS Early and 3-month-postpartum perineal pain was least for women who gave birth with an intact perineum . Spontaneous perineal tears were less painful than episiotomy . Sexual functioning was best for women with an intact perineum or perineal tears . Postpartum urinary and pelvic floor symptoms were similar in all perineal groups . At 3 months post partum those delivered with an intact perineum had the strongest pelvic floor musculature , those with episiotomy the weakest . Among primiparous women third- and fourth-degree tears were associated with median episiotomy ( 46/47 ) . After forceps births were removed and 21 other variables potentially associated within such tears were controlled for , episiotomy was strongly associated with third- and fourth-degree tears ( odds ratio + 22.08 , 95 % confidence interval 2.84 to 171.53 ) . Physicians using episiotomy at high rates also used other procedures , including cesarean section , more frequently . CONCLUSION Perineal and pelvic floor morbidity was greatest among women receiving median episiotomy versus those remaining intact or sustaining spontaneous perineal tears . Median episiotomy was causally related to third- and fourth-degree tears . Those using episiotomy at the highest rates were more likely use other interventions as well . Episiotomy use should be restricted to specified fetal-maternal indications typic abnormalities in early onset severe growth retardation ( Fisk et al. 1989 ; Nicolaides et al. 1989 ; Sipes et al. 1991 ) . However , since there is an overlap in mean corpuscular volume between triploid and chromosomally normal growth-retarded fetuses ( Nicolaides et al. 1989 ) it is necessary that the diagnosis is confirmed by cytogenetic analysis which usually takes 7 - 10 days . Using flow cytometry and st and ard DNA quantification techniques , which are now widely used in the clinical management of haematological and other neoplasias , it is possible to diagnose fetal triploidy from fetal blood , within l h of sampling Summary . Three methods of episiotomy repair were r and omly assigned after 900 consecutive deliveries . The three procedures were : ( 1 ) continuous No. 00‐plain catgut in the vagina ; No. 00‐plain catgut interrupted stiches in the perineal muscles and fascia , and No. 00‐nylon interrupted stiches in the skin . ( 2 ) The same technique as in ( l ) , but with No. 0‐polyglycolic acid ( Dexon ) in all layers . ( 3 ) The suture material as in ( 2 ) , but used with a subcuticular technique . The women treated with method 3 reported statistically significant less pain and disabilities in the early puerperium . Three months after delivery 262 women ( 33 % ) still had perineal complaints which could be directly related to the episiotomy in 25 % ( 8 % of total number ) . The group treated with method 3 had the best long‐term results and we conclude that the subcuticular technique using polyglycolic acid should be the method of choice One thous and women were allocated at r and om to one of two perineal management policies , both intended to minimise trauma during spontaneous vaginal delivery . In one the aim was to restrict episiotomy to fetal indications ; in the other the operation was to be used more liberally to prevent perineal tears . The result ant episiotomy rates were 10 % and 51 % respectively . An intact perineum was more common among those allocated to the restrictive policy . This group experienced more perineal and labial tears , however , and included four of the five cases of severe trauma . There were no significant differences between the two groups either in neonatal state or in maternal pain and urinary symptoms 10 days and three months post partum . Women allocated to the restrictive policy were more likely to have resumed sexual intercourse within a month after delivery . These findings provide little support either for liberal use of episiotomy or for cl aims that reduced use of the operation decreases postpartum morbidity We set out to compare a policy of two-layered postpartum perineal repair leaving the skin unsutured with a policy of three-layered repair , which involved skin closure . Parturients who sustained a second-degree tear or an episiotomy in four Nigerian centers were r and omised to have either a two-layered repair ( 417 women ) or a three-layered repair ( 406 women ) . Fewer women in the two-layered group reported perineal pain at 48 hours ( 57 % vs. 65 % , relative risk [ RR ] 0.87 , 95 % confidence interval [ CI ] 0.78 - 0.97 ) and 14 days postpartum ( 22 % vs. 28 % , RR 0.77 , CI 0.61 - 0.98 ) . The two-layered repair was also associated with reduced risk of suture removal ( 6 % vs. 10 % , RR 0.62 , CI 0.39 - 0.99 ) , and less superficial dyspareunia at 3 months ( 6 % vs. 12 % , RR 0.52 , CI 0.33 - 0.81 ) . The rates of wound healing were similar between the two groups . Leaving the skin unsutured during postpartum perineal repair reduces perineal pain and dyspareunia Commonly used suture material s and techniques for perineal repair following vaginal delivery were compared in a r and omized controlled trial involving 1574 women . Three comparisons were made using a modified factorial design . In the comparison of teflon‐coated polyglycolic acid ( Dexon plus ) with chromic catgut for repair of the vagina and deep perineal tissues there was no clear difference other than less short‐term analgesia being required in association with polyglycolic acid . Outcome was also similar after skin repair with either polyglycolic acid or chromic catgut or silk , although silk repair required more packets of material and was associated with delay in resuming sexual intercourse ; polyglycolic acid was more likely to need removal than chromic catgut but it appeared to reduce the need for resuturing . There was no clear difference between continuous subcuticular and interrupted transcutaneous sutures for repair of perineal skin STUDY OBJECTIVE To compare the continuous knotless technique of perineal repair with the interrupted method after spontaneous vaginal birth DESIGN A r and omized controlled trial . DESIGN CLASSIFICATION Canadian Task Force Classification I. SETTING This study was undertaken in a university hospital with more than 2200 deliveries per year . The static population of this district includes a wide range of socioeconomic classes and is predominately white . PATIENTS From May 1 to November 19 , 2003 , 214 primiparous women with a second-degree perineal tear or episiotomy were r and omly allocated to either the continuous knotless technique ( CKT ; n=107 ) or the interrupted technique ( IT ; n=107 ) suturing method . INTERVENTIONS The interrupted technique ( IT ) involves placing 3 layers of sutures whereas the continuous knotless technique ( CKT ) involves reapproximating vaginal trauma , perineal muscles , and skin with a loose , continuous , nonlocking technique . MEASUREMENTS AND MAIN RESULTS The primary outcomes of the study were perineal pain ( evaluated by visual analogue scale ) at 48 hours and day 10 and dyspareunia 3 months after delivery . Secondary outcomes included suture removal , wound dehiscence , analgesia use up to 48 hours , and satisfaction with repair established at 3 and 12 months after childbirth . At day 10 , 19 women had dropped out of the study . Significantly fewer women reported pain at 10 days with the CKT than with the IT ( 32.3 % vs 60.4 % ; p<.001 ) . Analgesia use up to 48 hours postpartum was less in the CKT group than in the IT group ( 33.6 % vs 54.2 % ; p<.05 ) . No difference was found in superficial dyspareunia at 3 months for the CKT versus the IT group . CONCLUSION The use of a continuous knotless technique for perineal repair is associated with less short-term pain than techniques with interrupted sutures |
1,683 | 24,979,314 | Exposure to KBM may initially be challenging for some people .
RESULTS were inconclusive for some outcomes , in particular against active controls .
KBM showed evidence of benefits for the health of individuals and communities through its effects on well-being and social interaction . | OBJECTIVE Kindness-based meditation ( KBM ) is a rubric covering meditation techniques developed to elicit kindness in a conscious way .
Some techniques , for example , loving-kindness meditation and compassion meditation , have been included in programs aim ed at improving health and well-being .
Our aim was to systematic ally review and meta-analyze the evidence available from r and omized controlled trials ( RCTs ) comparing the effects of KBM on health and well-being against passive and active control groups in patients and the general population . | OBJECTIVES The aim of these two studies was to evaluate the effectiveness of the Mindful Self-Compassion ( MSC ) program , an 8-week workshop design ed to train people to be more self-compassionate . METHODS Study 1 was a pilot study that examined change scores in self-compassion , mindfulness , and various wellbeing outcomes among community adults ( N = 21 ; mean [ M ] age = 51.26 , 95 % female ) . Study 2 was a r and omized controlled trial that compared a treatment group ( N = 25 ; M age = 51.21 ; 78 % female ) with a waitlist control group ( N = 27 ; M age = 49.11 ; 82 % female ) . RESULTS Study 1 found significant pre/post gains in self-compassion , mindfulness , and various wellbeing outcomes . Study 2 found that compared with the control group , intervention participants reported significantly larger increases in self-compassion , mindfulness , and wellbeing . Gains were maintained at 6-month and 1-year follow-ups . CONCLUSIONS The MSC program appears to be effective at enhancing self-compassion , mindfulness , and wellbeing The ability to accurately infer others ' mental states from facial expressions is important for optimal social functioning and is fundamentally impaired in social cognitive disorders such as autism . While pharmacologic interventions have shown promise for enhancing empathic accuracy , little is known about the effects of behavioral interventions on empathic accuracy and related brain activity . This study employed a r and omized , controlled and longitudinal design to investigate the effect of a secularized analytical compassion meditation program , cognitive-based compassion training ( CBCT ) , on empathic accuracy . Twenty-one healthy participants received functional MRI scans while completing an empathic accuracy task , the Reading the Mind in the Eyes Test ( RMET ) , both prior to and after completion of either CBCT or a health discussion control group . Upon completion of the study interventions , participants r and omized to CBCT and were significantly more likely than control subjects to have increased scores on the RMET and increased neural activity in the inferior frontal gyrus ( IFG ) and dorsomedial prefrontal cortex ( dmPFC ) . Moreover , changes in dmPFC and IFG activity from baseline to the post-intervention assessment were associated with changes in empathic accuracy . These findings suggest that CBCT may hold promise as a behavioral intervention for enhancing empathic accuracy and the neurobiology supporting it Recent empirical evidence supports the importance of adequate r and omization in controlled trials . Trials with inadequate allocation concealment have been associated with larger treatment effects compared with trials in which authors reported adequate allocation concealment . While that provides empirical evidence of bias being interjected into trials , trial investigators rarely document the sensitive details of subverting the intended purpose of r and omization . This article relates anonymous accounts run the gamut from simple to intricate operations , from transillumination of envelopes to search ing for code in the office files of the principal investigator . They indicate that deciphering is something more frequent than a rate occurrence . These accounts prompt some method ological recommendations to help prevent deciphering . R and omized controlled trials appear to annoy human nature -- if properly conducted , indeed they should Conditional goal setting ( CGS , the tendency to regard high order goals such as happiness , as conditional upon the achievement of lower order goals ) is observed in individuals with depression and recent research has suggested a link between levels of dispositional mindfulness and conditional goal setting in depressed patients . Since interventions which aim to increase mindfulness through training in meditation are used with patients suffering from depression it is of interest to examine whether such interventions might alter CGS . Study 1 examined the correlation between changes in dispositional mindfulness and changes in CGS over a 3 - 4 month period in patients participating in a pilot r and omised controlled trial of Mindfulness-Based Cognitive Therapy ( MBCT ) . Results indicated that increases in dispositional mindfulness were significantly associated with decreases in CGS , although this effect could not be attributed specifically to the group who had received training in meditation . Study 2 explored the impact of brief periods of either breathing or loving kindness meditation on CGS in 55 healthy participants . Contrary to expectation , a brief period of meditation increased CGS . Further analyses indicated that this effect was restricted to participants low in goal re-engagement ability who were allocated to loving kindness meditation . Longer term changes in dispositional mindfulness are associated with reductions in CGS in patients with depressed mood . However initial reactions to meditation , and in particular loving kindness meditation , may be counterintuitive and further research is required in order to determine the relationship between initial reactions and longer-term benefits of meditation practice B. L. Fredrickson 's ( 1998 , 2001 ) broaden- and -build theory of positive emotions asserts that people 's daily experiences of positive emotions compound over time to build a variety of consequential personal re sources . The authors tested this build hypothesis in a field experiment with working adults ( n = 139 ) , half of whom were r and omly-assigned to begin a practice of loving-kindness meditation . Results showed that this meditation practice produced increases over time in daily experiences of positive emotions , which , in turn , produced increases in a wide range of personal re sources ( e.g. , increased mindfulness , purpose in life , social support , decreased illness symptoms ) . In turn , these increments in personal re sources predicted increased life satisfaction and reduced depressive symptoms . Discussion centers on how positive emotions are the mechanism of change for the type of mind-training practice studied here and how loving-kindness meditation is an intervention strategy that produces positive emotions in a way that outpaces the hedonic treadmill effect Meditation practice s may impact physiological pathways that are modulated by stress and relevant to disease . While much attention has been paid to meditation practice s that emphasize calming the mind , improving focused attention , or developing mindfulness , less is known about meditation practice s that foster compassion . Accordingly , the current study examined the effect of compassion meditation on innate immune , neuroendocrine and behavioral responses to psychosocial stress and evaluated the degree to which engagement in meditation practice influenced stress reactivity . Sixty-one healthy adults were r and omized to 6 weeks of training in compassion meditation ( n=33 ) or participation in a health discussion control group ( n=28 ) followed by exposure to a st and ardized laboratory stressor ( Trier social stress test [ TSST ] ) . Physiologic and behavioral responses to the TSST were determined by repeated assessment s of plasma concentrations of interleukin (IL)-6 and cortisol as well as total distress scores on the Profile of Mood States ( POMS ) . No main effect of group assignment on TSST responses was found for IL-6 , cortisol or POMS scores . However , within the meditation group , increased meditation practice was correlated with decreased TSST-induced IL-6 ( r(p)=-0.46 , p=0.008 ) and POMS distress scores ( r(p)=-0.43 , p=0.014 ) . Moreover , individuals with meditation practice times above the median exhibited lower TSST-induced IL-6 and POMS distress scores compared to individuals below the median , who did not differ from controls . These data suggest that engagement in compassion meditation may reduce stress-induced immune and behavioral responses , although future studies are required to determine whether individuals who engage in compassion meditation techniques are more likely to exhibit reduced stress reactivity Decentering has been proposed as a potential mechanism of mindfulness-based interventions but has received limited empirical examination to date in experimental studies comparing mindfulness meditation to active comparison conditions . In the present study , we compared the immediate effects of mindful breathing ( MB ) to two alternative stress-management techniques : progressive muscle relaxation ( PMR ) and loving-kindness meditation ( LKM ) to test whether decentering is unique to mindfulness meditation or common across approaches . Novice meditators ( 190 female undergraduates ) were r and omly assigned to complete one of three 15-min stress-management exercises ( MB , PMR , or LKM ) presented by audio recording . Immediately after the exercise , participants completed measures of decentering , frequency of repetitive thoughts during the exercise , and degree of negative reaction to thoughts . As predicted , participants in the MB condition reported greater decentering relative to the other two conditions . The association between frequency of repetitive thought and negative reactions to thoughts was relatively weaker in the MB condition than in the PMR and LKM conditions , in which these two variables were strongly and positively correlated . Consistent with the construct of decentering , the relative independence between these two variables in the MB condition suggests that mindful breathing may help to reduce reactivity to repetitive thoughts . Taken together , results help to provide further evidence of decentering as a potential mechanism that distinguishes mindfulness practice from other credible stress-management approaches Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more This pilot study examined loving-kindness meditation ( LKM ) with 18 participants with schizophrenia-spectrum disorders and significant negative symptoms . Findings indicate that the intervention was feasible and associated with decreased negative symptoms and increased positive emotions and psychological recovery Most studies of meditation have focused on " actual affect " ( how people actually feel ) . We predict that meditation may even more significantly alter " ideal affect " ( how people ideally want to feel ) . As predicted , meditators ideally wanted to feel calm more and excited less than nonmeditators , but the groups did not differ in their actual experience of calm or excited states ( Study 1 ) . We ruled out self- selection and nonspecific effects by r and omly assigning participants to meditation classes , an improvisational theater class , or a no class control ( Study 2 ) . After eight weeks , meditators valued calm more but did not differ in their actual experience of calm compared with the other groups . There were no differences in ideal or actual excitement , suggesting that meditation selectively increases the value placed on calm . These findings were not due to expectancy effects ( Study 3 ) . We discuss the implication s of these findings for underst and ing how meditation alters affective life Objective To evaluate the reliability of risk of bias assessment s based on published trial reports , for determining trial inclusion in meta-analyses . Design Reliability evaluation of risk of bias assessment s. Data sources 13 published individual participant data ( IPD ) meta-analyses in cancer were used to source 95 r and omised controlled trials . Review methods Risk of bias was assessed using the Cochrane risk of bias tool ( RevMan5.1 ) and accompanying guidance . Assessment s were made for individual risk of bias domains and overall for each trial , using information from either trial reports alone or trial reports with additional information collected for IPD meta-analyses . Percentage agreements were calculated for individual domains and overall ( < 66%=low , ≥66%=fair , ≥90%=good ) . The two approaches were considered similarly reliable only when agreement was good . Results Percentage agreement between the two methods for sequence generation and incomplete outcome data was fair ( 69.5 % ( 95 % confidence interval 60.2 % to 78.7 % ) and 80.0 % ( 72.0 % to 88.0 % ) , respectively ) . However , percentage agreement was low for allocation concealment , selective outcome reporting , and overall risk of bias ( 48.4 % ( 38.4 % to 58.5 % ) , 42.1 % ( 32.2 % to 52.0 % ) , and 54.7 % ( 44.7 % to 64.7 % ) , respectively ) . Supplementary information reduced the proportion of unclear assessment s for all individual domains , consequently increasing the number of trials assessed as low risk of bias ( and therefore available for inclusion in meta-analyses ) from 23 ( 23 % ) based on publications alone to 66 ( 66 % ) based on publications with additional information . Conclusions Using cancer trial publications alone to assess risk of bias could be unreliable ; thus , review ers should be cautious about using them as a basis for trial inclusion , particularly for those trials assessed as unclear risk . Supplementary information from trialists should be sought to enable appropriate assessment s and potentially reduce or overcome some risks of bias . Furthermore , guidance should ensure clarity on what constitutes risk of bias , particularly for the more subjective domains BACKGROUND A growing body of research shows that mindfulness meditation can alter neural , behavioral and biochemical processes . However , the mechanisms responsible for such clinical ly relevant effects remain elusive . METHODS Here we explored the impact of a day of intensive practice of mindfulness meditation in experienced subjects ( n=19 ) on the expression of circadian , chromatin modulatory and inflammatory genes in peripheral blood mononuclear cells ( P BMC ) . In parallel , we analyzed a control group of subjects with no meditation experience who engaged in leisure activities in the same environment ( n=21 ) . P BMC from all participants were obtained before ( t1 ) and after ( t2 ) the intervention ( t2-t1=8h ) and gene expression was analyzed using custom pathway focused quantitative-real time PCR assays . Both groups were also presented with the Trier Social Stress Test ( TSST ) . RESULTS Core clock gene expression at baseline ( t1 ) was similar between groups and their rhythmicity was not influenced in meditators by the intensive day of practice . Similarly , we found that all the epigenetic regulatory enzymes and inflammatory genes analyzed exhibited similar basal expression levels in the two groups . In contrast , after the brief intervention we detected reduced expression of histone deacetylase genes ( HDAC 2 , 3 and 9 ) , alterations in global modification of histones ( H4ac ; H3K4me3 ) and decreased expression of pro-inflammatory genes ( RIPK2 and COX2 ) in meditators compared with controls . We found that the expression of RIPK2 and HDAC2 genes was associated with a faster cortisol recovery to the TSST in both groups . CONCLUSIONS The regulation of HDACs and inflammatory pathways may represent some of the mechanisms underlying the therapeutic potential of mindfulness-based interventions . Our findings set the foundation for future studies to further assess meditation strategies for the treatment of chronic inflammatory conditions BACKGROUND Children exposed to early life adversity ( ELA ) have been shown to have elevated circulating concentrations of inflammatory markers that persist into adulthood . Increased inflammation in individuals with ELA is believed to drive the elevated risk for medical and psychiatric illness in the same individuals . This study sought to determine whether Cognitively Based Compassion Training ( CBCT ) reduced C-reactive protein ( CRP ) in adolescents in foster care with high rates of ELA , and to evaluate the relationship between CBCT engagement and changes in CRP given prior evidence from our group for an effect of practice on inflammatory markers . It was hypothesized that increasing engagement would be associated with reduced CRP from baseline to the 6-week assessment . METHODS Seventy-one adolescents in the Georgia foster care system ( 31 females ) , aged 13 - 17 , were r and omized to either 6 weeks of CBCT or a wait-list condition . State records were used to obtain information about each participant 's history of trauma and neglect , as well as reason for placement in foster care . Saliva was collected before and again after 6 weeks of CBCT or the wait-list condition . Participants in the CBCT group completed practice diaries as a means of assessing engagement with the CBCT . RESULTS No difference between groups was observed in salivary CRP concentrations . Within the CBCT group , practice sessions during the study correlated with reduced CRP from baseline to the 6-week assessment . CONCLUSIONS Engagement with CBCT may positively impact inflammatory measures relevant to health in adolescents at high risk for poor adult functioning as a result of significant ELA , including individuals placed in foster care . Longer term follow-up will be required to evaluate if these changes are maintained and translate into improved health outcomes Purpose : Loving-kindness meditation has been used for centuries in the Buddhist tradition to develop love and transform anger into compassion . This pilot study tested an 8-week loving-kindness program for chronic low back pain patients . Method : Patients ( N = 43 ) were r and omly assigned to the intervention or st and ard care . St and ardized measures assessed patients ’ pain , anger , and psychological distress . Findings : Post and follow-up analyses showed significant improvements in pain and psychological distress in the loving-kindness group , but no changes in the usual care group . Multilevel analyses of daily data showed that more loving-kindness practice on a given day was related to lower pain that day and lower anger the next day . Conclusions : Preliminary results suggest that the loving-kindness program can be beneficial in reducing pain , anger , and psychological distress in patients with persistent low back pain . Implication s : Clinicians may find loving-kindness meditation helpful in the treatment of patients with persistent pain Although much research has examined the effect of income on happiness , we suggest that how people spend their money may be at least as important as how much money they earn . Specifically , we hypothesized that spending money on other people may have a more positive impact on happiness than spending money on oneself . Providing converging evidence for this hypothesis , we found that spending more of one 's income on others predicted greater happiness both cross-sectionally ( in a nationally representative survey study ) and longitudinally ( in a field study of windfall spending ) . Finally , participants who were r and omly assigned to spend money on others experienced greater happiness than those assigned to spend money on themselves CONTEXT Certain meditation practice s may effectively address spiritual needs near end-of-life , an often overlooked aspect of quality of life ( QOL ) . Among people subject to physical isolation , meditation benefits may be blunted unless physical contact is also addressed . OBJECTIVE To evaluate independent and interactive effects of Metta meditation and massage on QOL in people with acquired immunodeficiency syndrome ( AIDS ) . DESIGN R and omized controlled blinded factorial pilot trial conducted from November 2001 to September 2003 . SETTING An AIDS-dedicated skilled nursing facility in New Haven , Connecticut . PARTICIPANTS Fifty-eight residents ( 43 % women ) with late stage disease ( AIDS or comorbidity ) . INTERVENTIONS Residents were r and omized to 1 month of meditation , massage , combined meditation and massage , or st and ard care . The meditation group received instruction , then self-administered a meditation audiocassette daily . A certified massage therapist provided the massage intervention 30 minutes per day 5 days per week . OUTCOME MEASURE Changes on Missoula-Vitas QOL Index overall and transcendent ( spiritual ) scores at 8 weeks . RESULTS The combined group showed improvement in overall ( p = 0.005 ) and transcendent ( p = 0.01 ) scores from baseline to 8 weeks , a change significantly greater ( p < 0.05 ) than the meditation , massage , and control groups . CONCLUSIONS The combination of meditation and massage has a significantly favorable influence on overall and spiritual QOL in late-stage disease relative to st and ard care , or either intervention component alone The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials |
1,684 | 19,336,362 | The results from this review suggest that women with depressive symptomatology in the early postpartum period may be at increased risk for negative infant-feeding outcomes including decreased breastfeeding duration , increased breastfeeding difficulties , and decreased levels of breastfeeding self-efficacy .
There is also beginning evidence to suggest that depressed women may be less likely to initiate breastfeeding and do so exclusively .
Depressive symptomatology in the postpartum period negatively influences infant-feeding outcomes . | CONTEXT .
The negative health consequences of postpartum depression are well documented , as are the benefits of breastfeeding .
Despite the detailed research related to these maternal and infant health outcomes , the relationship between maternal mood and breastfeeding remains equivocal .
A qualitative systematic review was conducted to examine the relationship between postpartum depressive symptomatology and infant-feeding outcomes . | This prospect i ve study examined the relation of neonatal sucking to later feeding , postnatal growth , maternal postpartum depression , and feeding practice s. Healthy infants of at least 37 weeks gestational age were recruited . At 1 week of age , a strain-gage device was attached to the infant 's cheeks during sucking to identify sucking efficiency . Two-hundred and two infants ( 100 males , 102 females ; mean age 39.6 weeks , SD 1.1 weeks ) with efficient sucking and 207 ( 101 males , 106 females ; mean gestational age 39.4 weeks , SD 1.2 weeks ) with inefficient sucking were identified . Growth was measured at 2 , 6 , 10 , and 14 months . Mothers completed a feeding question naire and the Edinburgh Postnatal Depression Scale at the same testing points . While 18 infants ( 5 % ) showed a downward shift in growth , their clinical picture did not present as non-organic failure to thrive ( NFTT ) . Inefficient neonatal sucking did not predict postnatal growth , later feeding difficulties , nor maternal feeding practice s , but concurrent inefficient feeding did . Maternal depression did not affect feeding practice s , infant feeding abilities , nor growth , suggesting that the importance of maternal postpartum depression in association with feeding may be less than previously assumed . The term NFTT , therefore , merits reexamination and a more focused definition BACKGROUND Although much research has focused on identifying factors that influence breastfeeding initiation and duration , many high-risk factors are nonmodifiable demographic variables . Predisposing factors for low breastfeeding duration rates that are amenable to supportive interventions should be identified . The purpose of this study was to assess the effect of maternal confidence ( breastfeeding self-efficacy ) on breastfeeding duration . METHOD A prospect i ve survey was conducted with 300 women in the last trimester of pregnancy recruited from the antenatal clinic of a large metropolitan hospital in Brisbane , Australia . Telephone interviews were conducted at 1 week and 4 months postpartum to assess infant feeding methods and breastfeeding confidence using the Breastfeeding Self-Efficacy Scale . RESULTS Although 92 percent of participants initiated breastfeeding , by 4 months postpartum almost 40 percent discontinued and only 28.6 percent were breastfeeding exclusively ; the most common reason for discontinuation was insufficient milk supply . Antenatal and 1-week Breastfeeding Self-Efficacy Scale scores were significantly related to breastfeeding outcomes at 1 week and 4 months . Mothers with high breastfeeding self-efficacy were significantly more likely to be breastfeeding , and doing so exclusively , at 1 week and 4 months postpartum than mothers with low breastfeeding self-efficacy . CONCLUSIONS Maternal breastfeeding self-efficacy is a significant predictor of breastfeeding duration and level . Integrating self-efficacy enhancing strategies may improve the quality of healthcare that healthcare professionals deliver and may increase a new mother 's confidence in her ability to breastfeed , and to persevere if she does encounter difficulties One method used to determine utilization rates of cervical screening is women 's self-report . Few studies have assessed the accuracy of this measure -- none has been conducted in Australia -- although there are a number of reasons for suspecting its validity . This study examined and quantified the accuracy of self-report of Pap smear use among a r and omly selected sample of women from an Australian community . Accuracy of Pap smear utilization self-report within a three-year period was assessed by comparison with pathology records . Results indicated that almost half of the women who have not had Pap smears within three years will be missed by a self-report measure of utilization . Some implication s for the measurement and use of self-report data are discussed One hundred and forty-two women at six weeks postpartum were asked to complete Cox 's Edinburgh Postnatal Depression Scale . Thirty-eight scored positively for depression and 28 of these were followed up by a psychiatrist . Twenty-eight controls were r and omly selected from those who scored negatively . Numerous variables were considered , including the type of labour , whether the mother was breastfeeding or not , and the presence or absence of a psychiatric history . In addition the depressed group completed the Eysenck Personality Inventory . A past psychiatric history was found to be a very significant risk factor and there is a definite association between postnatal depression and delivery by forceps , vacuum or caesarian section . Maternal age and breastfeeding were not found to be of aetiological significance BACKGROUND Postnatal depression is a major public health problem . The aim of this study is to vali date the use of the Edinburgh Postnatal Depression Scale ( EPDS ) in the early postpartum , and to identify the markers for risk of postnatal depression . METHODS 815 women filled out an EPDS and general information question naire between the third and the fifth day postpartum . The women with an EPDS score of > 8 and a r and omized control group from those with scores of < 8 were contacted 8 weeks postpartum . 363 women therefore had a structured diagnostic interview by telephone at 8 weeks postpartum ( MINI-DSM-IV ) , without knowledge of their EPDS scores , to screen for a major or minor depressive episode . RESULTS The sensitivity of EPDS was measured as 0.82 [ 0.78 - 0.86 ] , with a positivity threshold of 9.5/30 . For an estimated prevalence for all depressive episodes of 16.1 % , the positive predictive value of EPDS was measured as 42.8 % [ 39.1 - 46.5 % ] . Multivariate risk analysis using logistical regression identified the following as risk markers for postnatal depression : previous history of depression ( postnatal or other ) , unemployment , premature delivery or stopping breast-feeding in the first month for non-medical reasons . CONCLUSION The use of EPDS between the third and fifth day postpartum is valid . An EPDS score of > 10 should be completed by a clinical assessment and suitable management . The risk markers identified here are clinical indices that can be used for first-line early screening by non-psychiatric health workers OBJECTIVE Breastfeeding rates fall short of goals set in Healthy People 2010 and other national recommendations . The current , national breastfeeding continuation rate of 29 % at 6 months lags behind the Healthy People 2010 goal of 50 % . The objective of this study was to evaluate associations between breastfeeding discontinuation at 2 and 12 weeks postpartum and clinician support , maternal physical and mental health status , workplace issues , and other factors amenable to intervention . METHODS A prospect i ve cohort study was conducted of low-risk mothers and infants who were in a health maintenance organization and enrolled in a r and omized , controlled trial of home visits . Mothers were interviewed in person at 1 to 2 days postpartum and by telephone at 2 and 12 weeks . Logistic regression modeling was performed to assess the independent effects of the predictors of interest , adjusting for sociodemographic and other confounding variables . RESULTS Of the 1163 mother-newborn pairs in the cohort , 1007 ( 87 % ) initiated breastfeeding , 872 ( 75 % ) were breastfeeding at the 2-week interview , and 646 ( 55 % ) were breastfeeding at the 12-week interview . In the final multivariate models , breastfeeding discontinuation at 2 weeks was associated with lack of confidence in ability to breastfeed at the 1- to 2-day interview ( odds ratio [ OR ] : 2.8 ; 95 % confidence interval [ CI ] : 1.02 - 7.6 ) , early breastfeeding problems ( OR : 1.5 ; 95 % CI : 1.1 - 1.97 ) , Asian race/ethnicity ( OR : 2.6 ; 95 % CI : 1.1 - 5.7 ) , and lower maternal education ( OR : 1.5 ; 95 % CI : 1.2 - 1.9 ) . Mothers were much less likely to discontinue breastfeeding at 12 weeks postpartum if they reported ( during the 12-week interview ) having received encouragement from their clinician to breastfeed ( OR : 0.6 ; 95 % CI : 0.4 - 0.8 ) . Breastfeeding discontinuation at 12 weeks was also associated with demographic factors and maternal depressive symptoms ( OR : 1.18 ; 95 % CI : 1.01 - 1.37 ) and returning to work or school by 12 weeks postpartum ( OR : 2.4 ; 95 % CI : 1.8 - 3.3 ) . CONCLUSIONS Our results indicate that support from clinicians and maternal depressive symptoms are associated with breastfeeding duration . Attention to these issues may help to promote breastfeeding continuation among mothers who initiate . Policies to enhance scheduling flexibility and privacy for breastfeeding mothers at work or school may also be important , given the elevated risk of discontinuation associated with return to work or school STUDY OBJECTIVE --Retrospective infant feeding data are important to the study of child and adult health patterns . The accuracy of maternal recall of past infant feeding events was examined and specifically the infant 's age when breast feeding was stopped and formula feeding and solid foods were introduced . DESIGN AND SETTING --The sample consisted of Bedouin Arab women ( n = 318 ) living in the Negev in Israel who were a part of a larger cohort participating in a prospect i ve study of infant health and who were delivered of their infants between July 1 and December 15 , 1981 . Data from interviews conducted 12 and 18 months postpartum were compared to the st and ard data collected six months postpartum . MAIN RESULTS --As length of recall increased there was a small increase in the mean difference , and its st and ard deviation , between the st and ard and recalled age when breast feeding was stopped and formula feeding and solid foods were started . Recall on formula feeding was less accurate than recall on solid foods and breast feeding . In particular , among those 61 % reporting formula use at the six month interview , 51 % did not recall introducing formula when interviewed at 18 months . The odds ratio ( 95 % CI ) of stunting versus normal length for age for formula fed versus breast fed infants based on recall data ( OR = 2.07 ; 95 % CI 0.82 - 5.22 ) differed only slightly from those based on the st and ard data ( OR = 2.21 ; 95 % CI 0.77 - 6.37 ) . The accuracy of a mother 's recall varied with her child 's nutritional status at the time of the interview , but not with other sociodemographic , infant , or interviewer characteristics . CONCLUSIONS --Retrospective infant feeding data based on maternal recall of events up to 18 months in the past can be used with confidence in epidemiological studies . However , data on formula feeding may not be as accurate as data on breast feeding and solid food feeding , and accuracy may decrease as length of recall increases Despite well-documented health benefits of breastfeeding for mothers and babies , most women discontinue breastfeeding before the recommended 12 months to 2 years . The purpose of this study was to assess the effect of modifiable antenatal variables on breastfeeding outcomes . A prospect i ve , longitudinal study was conducted with 300 pregnant , Australian women . Question naires containing variables of interest were administered to women during their last trimester ; infant feeding method was assessed at 1 week and 4 months postpartum . Intended breastfeeding duration and breastfeeding self-efficacy were identified as the most significant modifiable variables predictive of breastfeeding outcomes . Mothers who intended to breastfeed for < 6 months were 2.4 times as likely to have discontinued breastfeeding at 4 months compared to those who intended to breastfeed for > 12 months ( 35.7 % vs 87.5 % ) . Similarly , mothers with high breastfeeding self-efficacy were more likely to be breastfeeding compared to mothers with low self-efficacy ( 79.3 % vs 50.0 % ) . J Hum Lact . 20(1):30 - 38 Hormonal factors have been suggested as a cause of post-natal depression , but suckling frequency which is the major influence on hormone levels post-partum has not been considered in previous studies . Eighty-nine women who had taken part in a prospect i ve study of post-natal depression were asked about their feeding patterns 18 months after childbirth . Half the mothers who were breast feeding introduced solids or artificial milk feeds before 12 weeks and were likely to have lowered prolactin levels and increased ovarian follicular activity . Mothers who totally breastfed their babies for at least 12 weeks or who were on the pill , had a higher incidence of post-natal depression than those who were not on the pill or who partially breastfed . Among the 62 women who attempted breast feeding those most likely to have normal levels of endogenous hormones were those least likely to have depressive symptoms Purpose To examine patterns of exclusive breastfeeding , combination feeding , and exclusive bottle-feeding among a sample of women identified at 2–4 weeks postpartum with positive PPD symptoms . Study Design and Methods The sample included 122 women who were part of a larger study testing an intervention for promoting maternal-infant interaction among women with elevated PPD symptoms . Data were collected during three postpartum home visits . Demographic and feeding pattern data were described . Variables related to and predictors of feeding pattern were analyzed . The sample was compared to a r and om sample of postpartum women in New Engl and . Results Severity of depression was not significantly related to breastfeeding . Older maternal age , living with a partner , and higher income were positively related to breastfeeding . Compared to a r and om sample , the level of exclusive breastfeeding was significantly lower in this sample than the level of combination feeding . Clinical Implication sNurses should be involved in screening all prenatal and postpartum women for PPD symptoms , particularly when they present with breastfeeding difficulties , and refer for treatment when appropriate . For breastfeeding mothers , PPD treatment must include consideration of therapeutic options as well as implication s for the breastfeeding relationship . When appropriate treatment for PPD is being considered , thought should be given to the importance and value of breastfeeding to the mother Plasma cortisol , prolactin , oestrogen , progesterone , thyroxine , thyrotrophin ( TSH ) were collected from 23 pregnant , 70 postpartum women at 7 days postpartum , and 38 non-gravid controls . Sixty two postpartum women were screened for depression by the Edinburgh Postnatal Depression Scale ( EPDS ) on day 7 after delivery and 34 of them were assessed by the Present State Examination ( PSE ) at 8 + /- 2 weeks after delivery . Postpartum women had a significantly greater level of cortisol , prolactin , thyroxine and oestrogen than non-puerperal women . Postpartum women with current depression ( EPDS > or = 11 ) had significantly lower plasma prolactin levels than those without depression and those who developed depression within 6 - 10 weeks after delivery ( PSE level > or = 5 ) had significantly lower plasma prolactin and significantly greater progesterone levels than those who were not depressed . There were significant correlations between age and plasma cortisol and prolactin levels . Higher thyroxine levels predicted greater severity of concurrent symptoms of depression ( total EPDS score ) whilst higher progesterone and lower prolactin levels predicted the occurrence of depression ( total PSE score ) 6 - 10 weeks after delivery . Women who breastfed had significantly lower EPDS and total PSE scores and higher plasma prolactin levels than those who did not breastfed their infants whilst women who had previous episodes of depression had significantly greater EPDS and PSE scores , lower prolactin and higher TSH levels than those who had not suffered from previous episodes of depression Two studies examined the effects of breast-feeding on maternal stress and mood . In Experiment 1 , perceived stress in the past month was compared between 28 breast-feeding and 27 bottle-feeding mothers . Breast-feeding mothers reported less perceived stress , after controlling for demographic confounds . In Experiment 2 , mood ratings were assessed in the same 24 mothers both before and then after 1 breast-feeding and 1 bottle-feeding session . Breast-feeding was associated with a decrease in negative mood , and bottle-feeding was associated with a decrease in positive mood from pre- to postfeeding . Results indicated that breast-feeding buffers negative mood . These effects appeared to be attributable to the effects of breast-feeding itself and not solely to individual-differences factors |
1,685 | 30,216,478 | MT in patients with DLBCL achieving CR or PR after induction therapy did not affect OS , yet it decreased relapse rate and improved disease control at the cost of higher infection rate .
Our data do not support routine administration of MT in patients with DLBCL | R and omized trials of maintenance therapy ( MT ) in diffuse large B cell lymphoma ( DLBCL ) are inconclusive regarding its effect on overall survival ( OS ) and disease control .
We aim ed to examine the efficacy and safety of MT in this meta- analysis . | BACKGROUND This study compared the induction regimens doxorubicin , cyclophosphamide and etoposide ( ACE ) with doxorubicin , cyclophosphamide , vincristine , bleomycin and prednisone ( ACVBP ) before high-dose therapy ( HDT ) followed by autologous stem-cell transplantation ( ASCT ) for patients with poor-risk diffuse large B-cell lymphoma ( DLBCL ) . A second r and omisation compared rituximab with observation post-ASCT . MATERIAL S AND METHODS Four hundred and seventy-six patients < 60 years old with newly diagnosed CD20 + DLBCL were r and omised to induction with ACE or ACVBP . Three hundred and thirty responders received HDT followed by ASCT . After ASCT , 269 patients were re-r and omised to receive either maintenance rituximab or observation alone . R and omisation was stratified by the quality of response to ASCT . The primary end point of this study was event-free survival ( EFS ) . RESULTS At a median of 4 years ' follow-up from the second r and omisation , there was a trend ( P = 0.1 ) towards increased EFS for patients who received rituximab compared with observation . CONCLUSION The type of induction therapy ( ACVBP or ACE ) did not significantly affect overall survival at a median 51 months ' follow-up Background Patients with diffuse large B-cell lymphoma ( DLBCL ) with an International Prognostic Index ( IPI ) ≥3 are at higher risk for relapse after a complete response ( CR ) to first-line rituximab-based chemotherapy ( R-chemo ) . Everolimus has single-agent activity in lymphoma . PILLAR-2 aim ed to improve disease-free survival ( DFS ) with 1 year of adjuvant everolimus . Patients and methods Patients with high-risk ( IPI ≥3 ) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were r and omized to 1 year of everolimus 10 mg/day or placebo . The primary end point was DFS ; secondary end points were overall survival , lymphoma-specific survival , and safety . Results Between August 2009 and December 2013 , 742 patients were r and omized to everolimus ( n = 372 ) or placebo ( n = 370 ) . Median follow-up was 50.4 months ( range 24.0 - 76.9 ) . Overall , 47 % of patients were ≥65 years , 50 % were male , and 42 % had an IPI of 4 or 5 . 48 % and 67 % completed everolimus and placebo , respectively . Primary reasons for everolimus discontinuation versus placebo were adverse events ( AEs ; 30 % versus 12 % ) and relapsed disease ( 6 % versus 13 % ) . Everolimus did not significantly improve DFS compared with placebo ( hazard ratio 0.92 ; 95 % CI 0.69 - 1.22 ; P = 0.276 ) . Two-year DFS rate was 77.8 % ( 95 % CI 72.7 - 82.1 ) with everolimus and 77.0 % ( 95 % CI 72.1 - 81.1 ) with placebo . Common grade 3/4 AEs with everolimus were neutropenia , stomatitis , and decreased CD4 lymphocytes . Conclusions Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR . Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained . Clinical Trials.gov NCT00790036 Purpose The st and ard treatment of patients with diffuse large B-cell lymphoma ( DLBCL ) is rituximab in combination with cyclophosphamide , doxorubicin , vincristine , and prednisone ( R-CHOP ) . Lenalidomide , an immunomodulatory agent , has shown activity in DLBCL . This r and omized phase III trial compared lenalidomide as maintenance therapy with placebo in elderly patients with DLBCL who achieved a complete response ( CR ) or partial response ( PR ) to R-CHOP induction . Methods Patients with previously untreated DLBCL or other aggressive B-cell lymphoma were 60 to 80 years old , had CR or PR after six or eight cycles of R-CHOP , and were r and omly assigned to lenalidomide maintenance 25 mg/d or placebo for 21 days of every 28-day cycle for 24 months . The primary end point was progression-free survival ( PFS ) . Results A total of 650 patients were r and omly assigned . At the time of the primary analysis ( December 2015 ) , with a median follow-up of 39 months from r and om assignment , median PFS was not reached for lenalidomide maintenance versus 58.9 months for placebo ( hazard ratio , 0.708 ; 95 % CI , 0.537 to 0.933 ; P = .01 ) . The result was consistent among analyzed subgroups ( eg , male v female , age-adjusted International Prognostic Index 0 or 1 v 2 or 3 , age younger than 70 v ≥ 70 years ) , response ( PR v CR ) after R-CHOP , and positron emission tomography status at assignment ( negative v positive ) . With longer median follow-up of 52 months ( October 2016 ) , overall survival was similar between arms ( hazard ratio , 1.218 ; 95 % CI , 0.861 to 1.721 ; P = .26 ) . Most common grade 3 or 4 adverse events associated with lenalidomide versus placebo maintenance were neutropenia ( 56 % v 22 % ) and cutaneous reactions ( 5 % v 1 % ) , respectively . Conclusion Lenalidomide maintenance for 24 months after obtaining a CR or PR to R-CHOP significantly prolonged PFS in elderly patients with DLBCL Diffuse large B-cell lymphoma ( DLBCL ) is a heterogeneous entity , with patients exhibiting a wide range of outcomes . The addition of rituximab to CHOP chemotherapy (R-CHOP)has led to a marked improvement in survival and has called into question the significance of previously recognized prognostic markers . Since r and omized controlled trials of R-CHOP in DLBCL have included select subgroups of patients , the utility of the International Prognostic Index ( IPI ) has not been reassessed . We performed a retrospective analysis of patients with DLBCL treated with R-CHOP in the province of British Columbia to assess the value of the IPI in the era of immunochemotherapy . The IPI remains predictive , but it identifies only 2 risk groups . Redistribution of the IPI factors into a revised IPI ( R-IPI ) provides a more clinical ly useful prediction of outcome . The R-IPI identifies 3 distinct prognostic groups with a very good ( 4-year progression-free survival [ PFS ] 94 % , overall survival [ OS ] 94 % ) , good ( 4-year PFS 80 % , OS 79 % ) , and poor ( 4-year PFS 53 % , OS 55 % ) outcome , respectively ( P < .001 ) . The IPI ( or R-IPI ) no longer identifies a risk group with less than a 50 % chance of survival . In the era of R-CHOP treatment , the R-IPI is a clinical ly useful prognostic index that may help guide treatment planning and interpretation of clinical trials OBJECTIVES We conducted a r and omized clinical trial to evaluate the role of interferon alfa 2b ( IFN ) as maintenance therapy in patients with diffuse large B-cell lymphoma with high or high-intermediate clinical risk on complete remission ( CR ) after CHOP-BLEO regimens . METHODS Patients were initially treated with CHOP-BLEO regimens ( which include increased doses of cyclophosphamide and epirubicine , instead of doxorubicin ) . If the patients achieved CR they were r and omly assigned to receive either maintenance therapy with IFN 5.0 MU , three times at week by 1 yr , or no treatment ( control group ) . RESULTS Two hundred and twenty-three patients were considered as c and i date s for the study . They were of high ( 80 % ) or high-intermediate ( 20 % ) clinical risk ; additionaly most patients had poor prognostic factors such as high levels of beta 2 microglobulin , lactic dehydrogenase levels , bulky disease ( defined as a tumor mass > 10 cm ) or multiple extranodal involvement . In an intent-to-treat analysis all patients were evaluable to efficacy and toxicity . Median follow-up was 45 months , the estimated 5-yr overall survival and event-free survival ( EFS ) for patients who received IFN were 71 % ( 95 % confidence interval ( CI ) : 61 - 83 % ) and 57 % ( 95 % CI : 39 - 69 % ) , respectively , values which were not statistically different from the control group : 69 % ( 95 % CI : 63 - 79 % ) and 54 % ( 95 % CI : 37 - 63 % ) , respectively ( p=0.2 ) . Toxicity was mild . CONCLUSIONS These results suggest that IFN used as maintenance therapy at these doses and schedules is not useful in aggressive malignant lymphoma when more intensive chemotherapy has been employed during induction treatment . Nevertheless , follow-up is too short , and long-term follow-up would be necessary in order to draw definitive conclusions . Probably , an multicenter study is necessary to define the role of IFN as maintenance therapy in this patient setting Maintenance therapy in patients with aggressive malignant lymphoma using biological modifiers remains uncertain . We conducted a controlled clinical trial to evaluate the efficacy and toxicity of interferon-alpha 2b , cyclophosphamide , and prednisone as maintenance therapy in patients with aggressive diffuse large B cell lymphomas in complete remission after aggressive chemotherapy . In an intent-to-treat analysis , 169 patients were eligible for this study ; the end points were event-free survival ( EFS ) and overall survival ( OS ) . With a median follow-up of 49.3 months , no statistical differences were observed and actuarial curves at 5 years showed that EFS was 71 % ( 95 % confidence interval [ CI ] , 63 - 79 % ) for patients who received maintenance compared to 63 % ( 95 % CI , 59 - 71 % ) for patients in control group ( p = 0.05 ) . No statistical differences were observed in OS between maintenance arm : 84 % ( 95 % CI , 78 - 89 % ) and control group 83 % ( 95 % CI , 77 - 88 % ) in control group ( p = 0.2 ) . All patients received the maintenance therapy as planned and in time , thus dose intensity was considered 1.0 in all cases . Acute toxicity was mild , and no delay or suspension of treatment was necessary . Late toxicity was not evident until now . We conclude that use of maintenance therapy combining interferon-alpha 2b , cyclophosphamide , and prednisone is not useful in patients with aggressive lymphoma if they had been treated with aggressive combined chemotherapy To assess the efficacy and toxicity of interferon alfa 2b ( IFN ) as maintenance therapy in patients with malignant lymphoma on complete response after conventional chemotherapy we start a r and omized clinical trial . One hundred and seventy patients were r and omized to received either IFN 5.0 MU three time at week by one year or no further treatment , as control group . At a median follow-up of 9.0 years ( range 4.3 to 11 years ) median freedom from relapse ( FFR ) has not been reached in patients who received IFN , it is statistically significant to patients in control group with a median FFR of 60 months ( p < .001 ) . Actuarial curves show that at 10-years , 58 patients ( 66 % , 95 % confidence interval ( CI ) 53 % to 79 % ) remain in first remission , statistical different to control group 33 patients ( 40 % , 95 % Cl : 33 % to 57 % ) ( p < .001 ) . Event free survival ( EFS ) shown that a 10-years 63 patients ( 71 % , 95 % CI : 59 % to 81 % ) are alive free of disease in the IFN arm compared to only 38 patients ( 45 % , 95 % CI : 37 % to 57 % ) in the control group ( p < .001 ) . Toxicity was mild , 81 patients received the planned doses of IFN on time and 6 patients had transitory delay secondary to hematological toxicity ( grade 1 or 2 ) and completed the treatment on 13 months . No late side effects has been observed . After a long term follow-up we confirm that IFN used as maintenance therapy improves outcome in patients with aggressive malignant lymphoma who were in complete remission after conventional chemotherapy without excessive toxicity . We feld that IFN will be consider in controlled clinical trials to define the role of this therapeutic option Background : The correlation between efficacy end points in r and omized controlled trials ( RCTs ) of systemic therapy for non-Hodgkin 's lymphoma ( NHL ) was investigated to identify an appropriate surrogate end point for overall survival ( OS ) . Methods : RCTs of previously untreated NHL published from 1990 to 2009 were identified . Associations between absolute differences in efficacy end points were determined using nonparametric Spearman 's rank correlation coefficients ( rs ) . Results : Thirty-eight RCTs representing 85 treatment arms for aggressive NHL and 20 RCTs representing 42 arms for indolent NHL were included . For aggressive NHL , differences in 3-year progression-free survival (PFS)/event-free survival ( EFS ) were high correlated with differences in 5-year OS { rs of 0.90 [ 95 % confidence interval ( CI ) 0.73–0.96 ] } and linear regression determined that a 10 % improvement in 3-year EFS or PFS would predict for a 7 % ± 1 % improvement in 5-year OS . For indolent histology disease , differences in complete response were strongly correlated with differences in 3-year EFS [ rs 0.86 ( 95 % CI 0.35–0.97 ) ] , but there was no correlation between 3-year time-to-event end points and 5-year OS . Conclusions : Improvements in 3-year EFS/PFS are highly correlated with improvements in 5-year OS in aggressive NHL and should be explored as a c and i date surrogate end point . Definition of these relationships may inform future clinical trial design and interpretation of interim trial data PURPOSE The st and ard treatment for relapsed diffuse large B-cell lymphoma ( DLBCL ) is salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation ( ASCT ) . The impact of maintenance rituximab after ASCT is not known . PATIENTS AND METHODS In total , 477 patients with CD20(+ ) DLBCL who were in their first relapse or refractory to initial therapy were r and omly assigned to one of two salvage regimens . After three cycles of salvage chemotherapy , the responding patients received high-dose chemotherapy followed by ASCT . Then , 242 patients were r and omly assigned to either rituximab every 2 months for 1 year or observation . RESULTS After ASCT , 122 patients received rituximab , and 120 patients were observed only . The median follow-up time was 44 months . The 4-year event-free survival ( EFS ) rates after ASCT were 52 % and 53 % for the rituximab and observation groups , respectively ( P = .7 ) . Treatment with rituximab was associated with a 15 % attributable risk of serious adverse events after day 100 , with more deaths ( six deaths v three deaths in the observation arm ) . Several factors affected EFS after ASCT ( P < .05 ) , including relapsed disease within 12 months ( EFS : 46 % v 56 % for relapsed disease after 12 months ) , secondary age-adjusted International Prognostic Index ( saaIPI ) more than 1 ( EFS : 37 % v 61 % for saaIPI < 1 ) , and prior treatment with rituximab ( EFS : 47 % v 59 % for no prior rituximab ) . A significant difference in EFS between women ( 63 % ) and men ( 46 % ) was also observed in the rituximab group . In the Cox model for maintenance , the saaIPI was a significant prognostic factor ( P < .001 ) , as was male sex ( P = .01 ) . CONCLUSION In relapsed DLBCL , we observed no difference between the control group and the rituximab maintenance group and do not recommend rituximab after ASCT In the multicentre prospect i ve r and omized HD2002 trial , rituximab maintenance therapy ( 375 mg/m2 every 3 months for 2 years ) versus observation was evaluated for CD20 + B‐cell lymphoma . Out of 321 patients [ 161 r and omized to the treatment group ( TG ) , 160 to the observation group ( OG ) ] , 295 data sets were evaluable for statistical analysis . Estimated 5‐year relapse‐free survival ( RFS ) was 81 % in the TG and 70 % in the OG ( logrank test , P = 0·047 ) . In the diffuse large B‐cell lymphoma ( DLBCL ) subgroup ( n = 152 ) , 5‐year RFS was excellent , at 87 % in the TG and 84 % in the OG ( logrank test , P = 0·35 ) . Of note , only in male patients of the DLBCL subgroup was RFS significantly superior in the TG in comparison to the OG ( 5‐year RFS : 88 % vs. 74 % ; logrank test , P = 0·05 ) . Cox regression analysis showed a significant interaction between treatment and gender regarding overall survival ( OS ) ( P = 0·006 ) and RFS ( P = 0·02 ) , with a lower hazard in females than males in the OG [ OS : hazard ratio ( HR ) ( female : male ) = 0·11 ; 95 % confidence interval ( CI ) = 0·00–1·03 ; RFS : HR ( female : male ) = 0·27 ; 95 % CI = 0·05–0·97 ] , and no significant differences between males and females in the TG . We conclude that Rituximab maintenance therapy improves survival in male patients with DLBCL PURPOSE To address early and late treatment failures in older patients with diffuse large B-cell lymphoma ( DLBCL ) , we design ed a two-stage r and omized trial of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) versus rituximab plus CHOP ( R-CHOP ) , with a second r and om assignment to maintenance rituximab ( MR ) or observation in responding patients . PATIENTS AND METHODS Untreated DLBCL patients who were 60 years or older were r and omly assigned to R-CHOP ( n = 318 ) or CHOP ( n = 314 ) ; 415 responders were r and omly assigned to MR ( n = 207 ) or observation ( n = 208 ) . The primary end point was failure-free survival ( FFS ) . All P values were two sided . RESULTS Three-year FFS rate was 53 % for R-CHOP patients and 46 % for CHOP patients ( P = .04 ) at a median follow-up time of 3.5 years . Two-year FFS rate from second r and om assignment was 76 % for MR compared with 61 % for observation ( P = .009 ) . No significant differences in survival were seen according to induction or maintenance therapy . FFS was prolonged with MR after CHOP ( P = .0004 ) but not after R-CHOP ( P = .81 ) with 2-year FFS rates from second r and om assignment of 77 % , 79 % , 74 % , and 45 % for R-CHOP , R-CHOP + MR , CHOP + MR , and CHOP , respectively . In a secondary analysis excluding MR patients , R-CHOP alone reduced the risks of treatment failure ( P = .003 ) and death ( P = .05 ) compared with CHOP alone . CONCLUSION Rituximab administered as induction or maintenance with CHOP chemotherapy significantly prolonged FFS in older DLBCL patients . After R-CHOP , no benefit was provided by MR . These results , which are consistent with an additive effect of rituximab , suggest that future studies could focus on maintenance strategies with novel agents as well as new induction therapies BACKGROUND Although many patients with intermediate- grade or high- grade ( aggressive ) non-Hodgkin 's lymphoma are cured by combination chemotherapy , the remainder are not cured and ultimately die of their disease . The Ann Arbor classification , used to determine the stage of this disease , does not consistently distinguish between patients with different long-term prognoses . This project was undertaken to develop a model for predicting outcome in patients with aggressive non-Hodgkin 's lymphoma on the basis of the patients ' clinical characteristics before treatment . METHODS Adults with aggressive non-Hodgkin 's lymphoma from 16 institutions and cooperative groups in the United States , Europe , and Canada who were treated between 1982 and 1987 with combination-chemotherapy regimens containing doxorubicin were evaluated for clinical features predictive of overall survival and relapse-free survival . Features that remained independently significant in step-down regression analyses of survival were incorporated into models that identified groups of patients of all ages and groups of patients no more than 60 years old with different risks of death . RESULTS In 2031 patients of all ages , our model , based on age , tumor stage , serum lactate dehydrogenase concentration , performance status , and number of extranodal disease sites , identified four risk groups with predicted five-year survival rates of 73 percent , 51 percent , 43 percent , and 26 percent . In 1274 patients 60 or younger , an age-adjusted model based on tumor stage , lactate dehydrogenase level , and performance status identified four risk groups with predicted five-year survival rates of 83 percent , 69 percent , 46 percent , and 32 percent . In both models , the increased risk of death was due to both a lower rate of complete responses and a higher rate of relapse from complete response . These two indexes , called the international index and the age-adjusted international index , were significantly more accurate than the Ann Arbor classification in predicting long-term survival . CONCLUSIONS The international index and the age-adjusted international index should be used in the design of future therapeutic trials in patients with aggressive non-Hodgkin 's lymphoma and in the selection of appropriate therapeutic approaches for individual patients Background Follicular lymphoma is the second most common non-Hodgkin lymphoma in the United States and Europe . However , most of the prospect i ve r and omized studies have very little follow-up compared to the long natural history of the disease . The primary aim of this study was to investigate the long-term survival of our series of patients with follicular lymphoma . Patients and methods A total of 1074 patients with newly diagnosed FL were enrolled . Patients diagnosed were prospect ively enrolled from 1980 to 2013 . Results Median follow-up was 54.9 months and median overall survival is over 20 years in our series . We analyzed the patients who are still alive beyond 10 years from diagnosis in order to fully assess the prognostic factors that condition this group . Out of 166 patients who are still alive after more than 10 years of follow-up , 118 of them ( 73 % ) are free of evident clinical disease . Variables significantly associated with survival at 10 years were stage < II ( p < 0.03 ) , age < 60 years ( p < 0.0001 ) , low FLIPI ( p < 0.002 ) , normal β2 microglobulin ( p < 0.005 ) , no B symptoms upon diagnosis ( p < 0.02 ) , Performance Status 0–1 ( p < 0.03 ) and treatment with anthracyclines and rituximab ( p < 0.001 ) , or rituximab ( p < 0.0001 ) . Conclusions A longer follow-up and a large series demonstrated a substantial population of patients with follicular lymphoma free of disease for more than 10 years PURPOSE To compare disease-free survival ( DFS ) after maintenance therapy with the selective protein kinase C β ( PKCβ ) inhibitor , enzastaurin , versus placebo in patients with diffuse large B-cell lymphoma ( DLBCL ) in complete remission and with a high risk of relapse after first-line therapy . PATIENTS AND METHODS This multicenter , phase III , r and omized , double-blind , placebo-controlled trial enrolled patients who were at high risk of recurrence after rituximab-cyclophosphamide , doxorubicin , vincristine , and prednisone ( R-CHOP ) . Patients ( N = 758 ) with stage II bulky or stage III to IV DLBCL , three or more International Prognostic Index risk factors at diagnosis , and a complete response or unconfirmed complete response after 6 to 8 cycles of R-CHOP were assigned 2:1 to receive oral enzastaurin 500 mg daily or placebo for 3 years or until disease progression or unacceptable toxicity . Primary end point was DFS 3 years after the last patient entered treatment . Correlative analyses of biomarkers , including cell of origin by immunohistochemistry and PKCβ expression , with efficacy outcomes were exploratory objectives . RESULTS After a median follow-up of 48 months , DFS hazard ratio for enzastaurin versus placebo was 0.92 ( 95 % CI , 0.689 to 1.216 ; two-sided log-rank P = .541 ; 4-year DFS , 70 % v 71 % , respectively ) . Independent of treatment , no significant associations were observed between PKCβ protein expression or cell of origin and DFS or overall survival . CONCLUSION Enzastaurin did not significantly improve DFS in patients with high-risk DLBCL after achieving complete response to R-CHOP . Achievement of a complete response may have abrogated the prognostic significance of cell of origin by immunohistochemistry Eighty-one patients with large-cell non-Hodgkin 's lymphoma achieving complete restaging verified remission after induction chemotherapy ( CHOP-Bleo or m-BACOD ) were r and omized to the following 3 arms : 1 . No further treatment ( observation ) . 2 . Early consolidation therapy with 6 courses of CVP ( cyclophosphamide , vincristine , prednisone ) given monthly . 3 . Maintenance therapy with cyclophosphamide and prednisone given every 6 weeks for 2 years . The relapse-free survival was better in the maintenance and consolidation arms than in the observation arm . The additional therapy given after the initial complete remission produced lasting disease control in a considerable number of patients and with acceptable toxicity . The authors feel that patients with large-cell lymphoma do not need more aggressive and toxic initial management because the use of maintenance therapy can increase the number of patients remaining in complete remission by more conventional , less toxic chemotherapy Purpose Overall survival ( OS ) is the definitive and best-established primary efficacy end point to evaluate diffuse large B-cell lymphoma ( DLBCL ) therapies , but it requires prolonged follow-up . An earlier end point assessed post-treatment would expedite clinical trial conduct and accelerate patient access to effective new therapies . Our objective was to formally evaluate progression-free survival ( PFS ) and PFS at 24 months ( PFS24 ) as surrogate end points for OS in first-line DLBCL . Patients and Methods Individual patient data were analyzed from 7,507 patients from 13 multicenter r and omized controlled trials of active treatment in previously untreated DLBCL , published after 2002 , with sufficient PFS data to predict treatment effects on OS . Trial-level surrogacy examining the correlation of treatment effect estimates of PFS/PFS24 and OS was evaluated using both linear regression ( R2WLS ) and Copula bivariable ( R2Copula ) models . Prespecified criteria for surrogacy required either R2WLS or R2Copula ≥ 0.80 and neither < 0.7 , with lower-bound 95 % CI > 0.60 . Results Trial-level surrogacy for PFS was strong ( R2WLS = 0.83 ; R2Copula = 0.85 ) and met the predefined criteria for surrogacy . At the patient level , PFS strongly correlated with OS . The surrogate threshold effect had a hazard ratio of 0.89 . Surrogacy was consistent across comparisons with or without rituximab and with rituximab maintenance trials . Trial-level surrogacy for PFS24 was relatively strong ( R2WLS = 0.77 ; R2Copula = 0.78 ) but did not meet prespecified criteria . At the patient level , PFS24 significantly correlated with OS . The surrogate threshold effect had an odds ratio of 1.51 . Conclusion This large pooled analysis of individual patient data supports PFS as a surrogate end point for OS in future r and omized controlled trials evaluating chemoimmunotherapy in DLBCL . Use of this end point may expedite therapeutic development with the intent of bringing novel therapies to this patient population years before OS results are mature |
1,686 | 30,988,882 | Conclusion The results of the three-Dimensional Versus St and ard miniplate showed that 3-dimensional miniplate is the best option for m and ibular fractures .
Regarding Lag Screws Versus Miniplates results of the meta- analysis found that the use of lag screws is superior to using miniplates in reducing the incidence of postoperative complications .
And in regards to locking miniplates versus non-locking miniplate , the analysis indicates that the 2.0-mm locking miniplate is a prospect i ve fixation system in the treatment of maxillofacial fractures | Background / purpose The aims of the present study were to 1 ) evaluate the clinical outcomes between different fixation methods in the management of m and ibular fractures ( MFs ) and 2 ) determine which fixation method is the best option for the treatment of m and ibular fractures . | Purpose The purpose of this study was to evaluate the efficacy and comparison between 2.0 mm locking plate system and 2.0 mm Champy ’s titanium mini plating system in m and ible fractures . Material s and Methods A total of 20 patients with m and ibular fractures were selected and divided into two groups A and B on r and omized basis . Group A was treated with open reduction internal fixation using 2.0 mm locking plates and group B with 2.0 mm Champy ’s titanium miniplates . All patients were followed up for 12 weeks postoperatively . Results Results of the study show less screw loosening , less precision in plate adaptation and less alteration of the osseous or occlusal relationship upon screw tightening in group A. Chi square test was applied to compare the results between the two groups . Statistical analysis did not show significant difference of incidence of malocclusion between the two groups ( p value = 0.606 ) . Statistical analysis using un-paired t test showed significant difference of working time between the two groups ( p value = 0.00296 ) . When comparing the overall complication rates according to plates used , the χ2 test showed no statistically significant difference between the locking and nonlocking plates ( p > 0.05 ) . Conclusion It is observed in our study that the locking plate/screw system offers significant advantages over the conventional plating system . The precise adaptation required for using conventional plates is not needed when this locking plate/screw system is used . Locking plate/screw system provides better stability than the conventional plate/screw system Purpose The purpose of this clinical study was to compare effectiveness of 2.0-mm locking miniplates and screws with 2.0-mm st and ard miniplates and screws in treating m and ible fractures . Patients and methods A r and omized prospect i ve study comprising of 40 sample s , where 20 patients ( group 1 ) were treated with locking plates and 20 patients ( group 2 ) were treated with st and ard miniplates . All the cases were evaluated for the type of fracture , need for the Intermaxillary Fixation ( IMF ) and its duration , duration of surgery , anatomic reduction , paresthesia / neurosensory changes , occlusal discrepancies , infection at the fracture site and any need for the removal of the plates and screws . Results In our study Road Traffic Accidents ( RTA ) accounted for the majority of patients 30 ( 70 % ) . RTA was more prevalent ( 52.5 % ) in 21–30 age group , with assault being more common ( 67 % ) in 25–35 years . There was a significant difference between group 1 and 2 in postoperative occlusal discrepancy and need for IMF ( p=0.008 ) . There was no significant difference in complication rates between group 1 and group 2 patients . Conclusion Locking plate/screw system proved to be more rigid than conventional plate/ screw system , thereby reducing the need and duration of IMF . However there was no significant difference in complication rates To compare and evaluate the effectiveness of 2.0 mm locking miniplates versus 2.0 mm st and ard miniplates in treatment of m and ible fractures . Sixty r and omly selected patients who sustained m and ibular fractures were selected for this study . The fractured fragments were stabilized using 2.0 mm locking miniplates in 30 cases and in the remaining 30 cases the fractured fragments were fixed with conventional 2.0 mm miniplates . Post-operative stability was assessed with radiographs at 7th day , 1st , and 3rd months . The stability of the reduced fracture was assessed clinical ly and both the types of plates were assessed with an OPG or conventional radiographs . This study shows favorable results on use of locking miniplates in m and ibular fractures . The results show that there were no significant differences in the post-operative complications between the conventional and the locking plate/screw m and ibular systems . The locking plate/screw system was more rigid than conventional plate/screw system , thereby reducing the need and duration of intermaxillary fixation ( IMF ) PURPOSE The aim of this follow-up study was to compare 3-dimensional ( 3D ) and st and ard ( Champy 's ) miniplate fixation in the management of m and ibular fractures , and to analyze advantages and disadvantages of one over the other . PATIENTS AND METHODS A prospect i ve r and omized clinical trial was carried out in patients with well-defined inclusion and exclusion criteria . Patients were followed for 2 months for wound dehiscence , infection , segmental mobility , postoperative occlusion , significant period of postoperative complications , and radiological evaluation of reduction and fixation . RESULTS Twenty patients were enrolled in both the groups with no case of wound dehiscence . In group 1 , 2 patients had mild segmental mobility ( P = .07 ) , 2 patients had surgical site infection ( P = .07 ) , and 2 patients involving mental nerve had involved roots of teeth ( P = .07 ) . Radiological evaluation did not show any statistically significant difference in reduction ( P = 1.4 ) , but showed a significant difference ( P = .03 ) in fixation between the 2 groups , especially in cases involving the mental nerve ( ie , fracture near or involving the mental foramen ) and oblique fractures . CONCLUSION Champy 's miniplate system is a better and easier method than the 3D miniplate system for fixation of m and ibular fractures . In comparison , the 3D miniplate system is unfavorable for use in cases of oblique fractures and those involving the mental nerve , and is also difficult to adapt . In most cases , it provides good stability but with excessive implant material because of extra vertical bars incorporated for countering the torque forces . However , operative time is less because of simultaneous stabilization at both superior and inferior borders Introduction The purpose of this study was to compare the outcome of open treatment of m and ibular fracture ( symphysis or parasymphysis ) using lag screw or mini plate clinical ly as well as radiologically in young ( age range 12–45 years ) and healthy individuals of poor socioeconomic status . Method This prospect i ve study was conducted on 30 patients diagnosed as cases of displaced m and ibular anterior fractures treated with open reduction and internal fixation . The patients were then r and omly allocated to either of two groups––Group A : Two 2.5 mm stainless steel lag screws were placed in 15 patients . Group B : Two 2.5 mm stainless steel mini plates were placed in 15 patients for the fixation of fractures . Subsequent follow up was done on 2nd , 4th , 6th and 8th week postoperatively . During every follow up patient was assessed clinical ly for infection , malocclusion , loosening of plate/screw , sensory disturbance , plate fracture , malunion/non-union , devitalisation of associated dentoalveolar segment and masticatory efficiency . Radiographs were taken if necessary and patients were further assessed for any complaint . Pain was objective ly measured using a visual analogue scale , bite force was measured using a bite force transducer at biweekly interval . The data collected was subjected to unpaired t test and paired t test for statistical analysis . Results During follow up period a significant improvement in bite force was present in both the groups , with more improvement seen in the lag screw group ( p < 0.01 ) . There was a significant pain reduction present in the lag screw group ( p < 0.01 ) and also masticatory efficiency showed a steadier improvement in lag screw group while mini plate group patients showed a tendency to masticate only food items of medium hard consistency . Conclusion The sample size is small to conclude lag screws are better than mini plates but the result of our study provides a basis for further studies done to conclude that the application of LAG SCREW is an effective , inexpensive , quick treatment modality to accelerate healing of fresh , displaced m and ibular anterior fracture This prospect i ve r and omized clinical trial compared the treatment outcomes of strut plate and Champy miniplate in fixation of m and ibular angle fractures . Patients with m and ibular angle fracture were consented and enrolled into this study . Exclusion criteria include patients with severely comminuted fractures . The patients were r and omly assigned to receive the strut plate or Champy miniplate for angle fracture fixation . Patient demographics , fracture characteristics , operative and postoperative outcomes were collected prospect ively . Statistical analysis was performed to evaluate the significance of the outcome . A total of 18 patients were included in this study and r and omly assigned to receive either the strut plate or Champy miniplate . Out of which five patients were excluded postoperatively due to complex fracture result ing in postoperative maxillom and ibular fixation . The final enrollment was 13 patients , N = 6 ( strut ) and N = 7 ( Champy ) . There was no statistically significant difference in the pretreatment variables . Nine of these patients had other associated facial fractures , including parasymphyseal and subcondylar fractures . Most of the ( 11 ) patients had sufficient follow-up after surgery . Both groups exhibited successful clinical unions of the m and ibular angle fractures . The complications associated with the m and ibular angle were 20 % in the strut plate group and 16.7 % in the Champy group . One patient in the strut plate group had a parasymphyseal infection , requiring hardware removal . The strut plate demonstrated comparable surgical outcome as the Champy miniplate . It is a safe and effective alternative for management of m and ibular angle fracture Introduction Three dimensional titanium plating system was developed by Farm and in 1995 to meet the requirements of semi rigid fixation with lesser complication . The purpose of this in vivo prospect i ve study was to evaluate and compare the clinical effectiveness of three dimensional and two dimensional Titanium miniplates for open reduction and fixation of m and ibular parasymphysis fracture . Material s and Methods Thirty patients with non-comminuted m and ibular parasymphysis fractures were divided r and omly into two equal groups and were treated with 2 mm 3D and 2D miniplate system respectively . All patients were systematic ally monitored at 1st , 2nd , 3rd , 6th week , 3rd and 6th month postoperatively . The outcome parameters recorded were severity of pain , infection , mobility , occlusion derangement , paresthesia and implant failure . The data so collected was analyzed using independent t test and Chi square test ( α = .05 ) . Results The results showed that one patient in each group had post-operative infection , occlusion derangement and mobility ( p > .05 ) . In Group A , one patient had paresthesia while in Group B , two patients had paresthesia ( p > .05 ) . None of the patients in both the groups had implant failure . There was no statistically significant difference between 3D and 2D miniplate system in all the recorded parameters at all the follow-ups ( p > .05 ) . Conclusion 3D miniplates were found to be better than 2D miniplates in terms of cost , ease of surgery and operative time . However , 3D miniplates were unfavorable for cases where fracture line was oblique and in close proximity to mental foramen , where they were difficult to adapt and more chances for tooth-root damage and inadvertent injury to the mental nerve due to traction This study evaluated the efficacy of a 2.0-mm locking plate/screw system compared with a 2.0-mm non-locking plate/screw system in m and ibular fractures . A prospect i ve r and omized clinical trial was conducted . Patients were r and omly assigned to receive 2.0-mm locking plates ( group A ) or 2.0-mm nonlocking plates ( group B ) . All patients were followed up for 12 weeks postoperatively . Complications were analysed according to the type of plate used and the site of fracture . Fifty patients with 76 fractures met the inclusion criteria . Thirty-six fracture sites were treated with 2.0-mm locking plates and 40 with 2.0-mm nonlocking plates . The number of patients requiring postoperative maxillom and ibular fixation was significantly higher in group B ( p < 0.01 ) ; seven complications occurred representing 9 % of the total . Two complications occurred in the locking group and five in the nonlocking group with complication rates equalling 6 % and 13 % , respectively . When comparing the overall complication rates according to plates used , the χ(2 ) test showed no statistically significant difference between the locking and nonlocking plates ( p > 0.05 ) . In conclusion , m and ible fractures treated with 2.0-mm locking plates and 2.0-mm nonlocking plates present similar short-term complication rates The objective of this study is to analyze the difference in bite forces in patients treated for m and ibular fractures with 2.0 mm conventional and locking titanium plating system . A r and omized study was performed for the treatment of fractures of m and ible . In this study , 20 adult patients with isolated m and ibular fracture were included . The patients were r and omly allocated into two groups , that is , Group I-2.0 mm nonlocking ( traditional ) and Group II-2.0 mm locking plates . Bite force was evaluated at 1st , 3rd , and 6th weeks . Comparison of all the assessed parameters between both the groups depicted no significant difference in terms of pain , swelling including the incidence of infection , paresthesia , and hardware failure . Although same was true in case of bite force between both the groups at various time intervals , there was statistically significant increase in the bite force within the group comprising patients in whom locking plates was used between 1st and 3rd weeks follow-up period and highly significant increase in bite force between 1st and 6th weeks of follow-up period . The rapid improvement of bite force values when locking plates were used implies that the locking plate can be used in preference to conventional plates to achieve early mobilization with assured stability in the treatment of m and ibular fractures Objective To compare the efficacy and surgical outcome of treatment of anterior m and ibular fracture using either 2.0 mm titanium miniplate or 2.4 mm titanium lag screw technique . Material s and Methods A total of 30 patients were managed by open reduction and internal fixation utilizing the miniplate and lag screw technique for fractures of anterior m and ible . The patients were r and omly divided into two groups . Group I : ( 15 patients ) were treated with Leibinger , 2.0 mm titanium mini plates system with self-tapping screws and Group II : ( 15 patients ) were treated with 2.4 mm cortical lag screw ( Synthes ) . Intraoperatively duration of surgery was measured from the time incision was placed till the closure of wound . Subsequent follow up was done at 3 , 6 , 12 , 24 weeks , postoperatively . During every follow up , patients were assessed clinical ly for malocclusion , neurosensory deficit , biting efficiency , implant failure , mal-union/non-union . Pre and postoperative radiographs were taken to assess the gap between fracture segments . Results were evaluated using Chi square and the unpaired t test . Results In our study , the mean duration of surgery ( hours ) was 1.97 ± 0.52 for group I and 1.26 ± 0.55 for group II . The difference was found to be statistically significant ( p value 0.001 ) . i.e. more time was taken in case of surgery with mini-plates when compared to the lag screw . Short surgical procedure reduces the incidence of infectious complications , which significantly lowers the financial burden . The mean post-operative radiographic distance between all measuring points were considerably more in case of mini-plate group as compared to lag screw group . Lag screw group showed faster improvement in terms of biting efficiency as compared to mini-plate group which showed a tendency to masticate only medium hard food items by 24 weeks . In both groups , no postoperative malocclusion was noted . In initial weeks , neurosensory deficit was seen more in mini-plate group as compared to lag screw group but after six weeks all patients showed improvement in neurosensory function without any permanent nerve damage . Conclusion According to this prospect i ve study , rigid internal fixation provided by lag screw technique for anterior m and ibular fracture offers several advantages over conventional bone plating . It is an excellent means of achieving rapid and safe fixation which is followed by primary bone healing in anterior m and ibular fractures , without any major complications Introduction The purpose of this retrospective study is to evaluate the efficacy of the 2.0-mm locking miniplate/screw system in comparison to the 2.0-mm nonlocking miniplate/screw system in mirror image m and ibular fractures . Material and method A retrospective clinical trial was review ed in the Department of Oral and Maxillofacial Surgery , Government Dental College , Pt . B.D. Sharma University of Health Sciences Rohtak for a period of 30 months ( June 2007 to December 2009 ) . A total of 30 patient pairs with isolated identical m and ibular fracture ( single or multiple ) having 88 fractures were analyzed . Results A total of 11 complications that occurred represented 12.5 % of the total . Six complications occurred at angle , three in the body and two at parasymphysis . Four complications occurred in the locking group and seven in the nonlocking group , with complication rates accounting for 9 % and 16 % , respectively . When comparing the overall complication rates according to plates used , the chi-square test showed no statistically significant difference between the locking and nonlocking plates ( p > 0.05 ) . Discussion M and ible fractures treated with the 2.0-mm locking plates and the 2.0-mm nonlocking plates present similar short-term complication rates Aim : To compare and evaluate the treatment outcome and postoperative complications in m and ibular fractures using 2- and 3-dimensional miniplates . Material s and Methods : This study consisted of a sample of 28 patients ( 40 fracture sites ) divided r and omly but equally ( single-blind control trial study ) into two groups . Each group contains 14 patients ( 20 similar fracture sites in each group ) . Group 1 was treated with open reduction and internal fixation using 3-dimensional ( 3-D ) miniplates . Group II was treated using 2-dimensional ( 2-D ) 2-mm miniplates . Results : Out of 14 patients treated by conventional 2-mm miniplates , 2 patients developed occlusal discrepancy , another 2 had postoperative mobility at fracture site , and 1 developed plate failure and subsequent infection , which was treated by removal of the plate under antibiotic coverage . One patient treated by 3-dimensional plates had tooth damage . Statistical Analysis : Chi-square test . Conclusion : The results of this study suggested that the treatment of m and ibular fractures ( symphysis , parasymphysis , and angle ) with 3-dimensional plates provided 3-dimensional stability and carried low morbidity and infection rates . The only probable limitations of 3-dimensional plates were excessive implant material due to the extra vertical bars incorporated for countering the torque forces Aims and Objectives To compare and evaluate the variation in recorded bite forces in patients with m and ibular fractures undergoing open reduction and rigid internal fixation using st and ard 2.0 versus 2.0 mm locking miniplates . Material s and Methods A prospect i ve r and omized study was conducted for the treatment of m and ibular fractures . Twenty adult patients with 31 m and ibular fractures requiring an open reduction and internal fixation were included in the study . The sample was divided into two groups depending upon whether the patients received 2.0 mm non-locking ( st and ard ) or 2.0 mm locking miniplates for rigid fixation respectively . Bite force was evaluated at 1st , 3rd and 6th week after the open reduction and rigid fixation using miniplates . Results A statistically significant difference was not found in the clinical parameters such as pain , swelling , infection , paresthesia , hardware failure , and mobility between the fracture segments . The results showed that amongst locking vs non-locking miniplates , the former showed a greater bite force enhancement when compared to baseline values(post-trauma).A comparison between 2nd day post-operative vs 6th week post-operative values showed a significant increase in bite force in Group 1 ( non-locking ) ( p < 0.05 ) whereas the values Were highly significant ( p < 0.001 ) in Group 2 ( locking Plate ) . Conclusion The findings were suggestive that the efficacy of locking miniplates plate in m and ibular fracture was superior in terms of bearing the masticatory loads during osteo synthesis of the fracture . However , the clinical results were almost similar to those seen with non-locking miniplate osteo synthesis PURPOSE The aim of this follow up clinical study was to compare and evaluate the effectiveness of 2 mm 4 holed 3-dimensional ( 3D ) locking titanium miniplates over st and ard miniplate fixation using Champy 's technique in the management of interforaminal m and ibular fractures . PATIENTS AND METHODS A prospect i ve r and omized double blind clinical trial was carried out in patients with well defined inclusion and exclusion criteria . Patients were followed for a period of 2 months at the intervals of 1 week , 2 weeks , 4 weeks , 6 weeks and 2 months by a blinded senior oral surgeon for wound dehiscence , infection , postoperative occlusion , significant postoperative complications , need for post-operative inter maxillary fixation and radiological evaluation of reduction , fixation . RESULT 10 patients were enrolled in both the groups in this preliminary report with no case of clinical ly significant postoperative complications . In comparison , 3D locking plates were economical , easy to adapt , required less operating time , and provided better stability . However , 2 patients in group 1 ( 3D locking plates ) with severely displaced unfavourable fractures required 6 holed plates or more for adequate stability . CONCLUSION Because of its added advantages and encouraging results in comparison to st and ard miniplate , we suggest use of 3D 4 holed locking 2 mm titanium miniplate for the management of isolated moderately displaced m and ibular fractures in inter mental foramen region Purpose To compare the efficacy of the 3D miniplates to st and ard miniplates in the osteo synthesis of m and ibular symphysis and parasymphysis fractures on the basis of clinical parameters and radiographic evaluation . Patients and Methods A prospect i ve r and omized clinical trial was conducted to treat consecutive m and ibular symphysis and parasymphysis fractures . The patients were r and omly divided into 2 groups . The patients underwent osteo synthesis in group A with 3D titanium miniplates and in group B with conventional titanium miniplates . The cause of trauma , the number of days from injury to surgery , average age and gender were all review ed . The assessment of the patients was done at 1 , 3 , and 6 weeks and 3 months using the clinical parameters and radiographic evaluation . Results Eighty patients with isolated symphysis or parasymphysis fracture met the inclusion criteria . In our study , a statistically significant difference was not found in the clinical parameters such as pain , swelling , infection , paresthesia , hardware failure , and mobility between the fracture segments . Similarly Radiological evaluation did not show any statistically significant difference in reduction between the 2 groups . 3D plates are difficult to adapt and use sometimes , but operative time is less with them in treatment of symphysis and parasymphysis fractures . Conclusion The use of 3D miniplates for symphysis and parasymphysis fracture fixation was efficacious enough to bear the masticatory load during osteo synthesis of the fracture . Although 3D miniplate system is difficult to adapt and difficult to use in cases of fractures involving the mental nerve , they provide the advantage of less operative time and less implant material in treatment of symphysis and parasymphysis fracture , with clinical results almost similar to those seen with conventional miniplate osteo synthesis PURPOSE This laboratory study compared the performance of locking versus nonlocking Synthes ( Synthes , Paoli , PA ) 2-mm m and ibular fixation plates . The purpose of the study was to determine if there are physical or mechanical properties to support the use of one rigid fixation device over the other . MATERIAL S AND METHODS A bovine rib model was selected for this study because they closely approximate characteristics of the human m and ible . Two experimental groups composed of 10 locking and 10 nonlocking 2-mm plates were secured to r and omly selected osteotomized bovine ribs using 10-mm monocortical screws . The specimens were loaded using a 4-point bending system to the point of failure using a MTS model 309.00 servo-hydraulic testing system ( MTS Systems Corp , Eden Prairie , MN ) with a custom fabricated fixator . The data was obtained with TestStar 2 version 4.0 and TestWare Sx 4.0 software ( MTS Systems Corp ) , and analyzed to determine if there was any difference in performance between the 2 m and ibular plate design s. RESULTS Overall , there were no statistically significant differences between the locking and conventional 2-mm m and ibular plate . Of the 20 sample s tested , 1 ( nonlocking ) had a unique early screw failure ( pullout ) inconsistent with any other sample s and was not analyzed . Of the remaining 19 sample s , 17 produced a yield failure , bend , or stretch rather than a plate fracture . Both of the plate fractures occurred in the nonlocking plates . Although the data suggested that this mode of failure was more common in nonlocking plates , the difference between both groups in the mode of failure did not achieve statistical significance ( chi2 = 2.0 , P = .16 ) . Thus , yield was the predominant mode of failure for both types of devices . The force at which each device failed was also similar in both groups . The force of failure for the nonlocking plates was 559.9 N ( SD = 247.9 ) , whereas the locking plate failure strength was 637.8 N ( SD = 276.3 ; t ( 17 ) = 0.6 , P = .53 ) . The results indicated that there was no suggestion that one plate might be stronger than the other . CONCLUSIONS In this laboratory model , no significant differences were found between the 2 types of m and ibular plates . Although studies have shown the locking system to be more rigid , this study suggested that the type and degree of failure are more likely related to bone quality and surgical technique when using the 2-mm m and ibular plate . Additional prospect i ve studies are needed to correlate these results in patient models PURPOSE The aim of this study was to compare efficacy between the single non-compression titanium miniplate and single three-dimensional titanium miniplate in m and ibular angle fracture treatment . METHOD AND MATERIAL S A prospect i ve study of 20 patients with m and ibular angle fractures . Patients were r and omly categorized into two groups with 10 patients in each group . Group-I patients were treated with single 2.0 mm conventional titanium miniplate , Group-II patients were treated with single 2.0 mm three-dimensional titanium miniplate according to Champy 's principles . Parameters such as stability of fracture fragments , occlusion , mouth opening , additional fixation required and complications were evaluated at different time intervals . RESULTS In Group-I , about 40 % ( n=4 ) of patients showed unstable fracture fragments on immediate postoperative day whereas in Group-II only 10 % ( n=1 ) of patients with fracture instability . In Group-I , 30 % ( n=3 ) had mild occlusal derangement and 20 % ( n=2 ) had deranged occlusion on immediate postoperative day , where as in Group-II only 20 % ( n=2 ) of patients had mild occlusal derangement . Additional fixation required in 30 % ( n=3 ) of patients in group-I , and 10 % ( n=1 ) in Group-II . 20 % ( n=2 ) of patients in Group-I developed infection . All patients in both the groups had inadequate mouth opening on immediate post operative day , later resumed normal mouth opening . 10 % ( n=1 ) in group-I and 20 % ( n=2 ) of patients in group-II presented with postinjury/preoperative inferior alveolar nerve sensory disturbance with no incidence of postoperative sensory disturbance . None of the patients in both the groups had malunion , nonunion , plate fracture , and loosening of plates and screws . CONCLUSION 3-D titanium miniplates showed more favorable results compared to single conventional titanium miniplate with respect to initial interfragmentary stability and complications Objective The aim of this study was to compare conventional miniplate ( Champy ’s ) and 3-dimensional miniplate fixation in the management of m and ibular fracture . Study Design Prospect i ve study . Setting The study was carried out in the Department of Oral and Maxillofacial Surgery , Govt . Dental College , Pt . B.D. Sharma University of Health Sciences , Rohtak , India . Subjects and Methods A prospect i ve r and omized clinical trial was carried out in 50 patients . Patients were r and omly assigned to receive a 2.0-mm 3-dimensional miniplate ( group A ) or a 2.0-mm conventional miniplate ( group B ) . All patients were followed up for 12 weeks postoperatively . Complications were analyzed according to the type of plate used and the site of fracture . Results Twenty-eight fracture sites were treated with the 3-dimensional miniplate and 28 with the conventional miniplate . Five complications occurred , representing 8.9 % of the total . Two complications occurred in group A and 3 in group B , with complication rates equaling 7.14 % and 10.71 % , respectively . When comparing the overall complication rates according to plates used , the χ2 test showed no statistically significant difference between the 2 groups ( P > .05 ) . Conclusion No major difference in terms of treatment outcome is observed in both systems , and both are equally effective in managing m and ibular fracture |
1,687 | 20,393,941 | MAIN RESULTS We included 38 studies ( 3679 women).Nine studies included pregnancies after intrauterine deaths , five studies included termination of pregnancies because of fetal anomalies when the fetus was still alive and the rest ( 24 ) presented the pooled data for intrauterine deaths , fetal anomalies and social reasons .When compared with agents that have traditionally been used to induce labour in this setting ( for example , gemeprost , prostagl and in E(2 ) and prostagl and in F(2alpha ) ) , vaginal misoprostol is as effective in ensuring vaginal birth within 24 hours , with a similar induction to birth interval .
Vaginal misoprostol is associated with a reduction in the occurrence of maternal gastrointestinal side effects such as nausea , vomiting and diarrhoea when compared with other prostagl and in preparations .
While the different treatments involving various prostagl and in preparations appear comparable for the reported outcomes , the information available regarding rare maternal complications , such as uterine rupture , is limited .
The use of vaginal misoprostol in the termination of second and third trimester of pregnancy is as effective as other prostagl and in preparations ( including cervagem , prostagl and in E(2 ) and prostagl and in F(2alpha ) ) , and more effective than oral administration of misoprostol . | BACKGROUND A woman may need to give birth prior to the spontaneous onset of labour in situations where the fetus has died in utero ( also called a stillbirth ) , or for the termination of pregnancy where the fetus , if born alive would not survive or would have a permanent h and icap .
Misoprostol is a prostagl and in medication that can be used to induce labour in these situations .
OBJECTIVES To compare the benefits and harms of misoprostol to induce labour to terminate pregnancy in the second and third trimester for women with a fetal anomaly or after intrauterine fetal death when compared with other methods of induction of labour . | OBJECTIVE The purpose of this study was to compare the efficacy and side effects of two different misoprostol regimens for second-trimester pregnancy termination . STUDY DESIGN We performed a r and omized clinical trial in patients who were at 14 to 23 weeks of gestation and who were admitted for medical termination of pregnancy . All patients received 800 microg of vaginal misoprostol and were assigned r and omly to 400 microg of oral misoprostol or 400 microg of vaginal misoprostol every 8 hours . Efficacy and side effects were compared . The mean induction time of the study group was compared with that of an historic control group that had received 400 microg vaginally every 12 hours . RESULTS Forty-three women were assigned r and omly , 22 women to vaginal misoprostol and 21 women to oral misoprostol . Induction time and hospital stay were slightly shorter for the oral group ; however , the differences were not significant . Side effects were similar for both groups . CONCLUSION After an initial 800 microg dose of vaginal misoprostol , a regimen of 400 microg of oral misoprostol every 8 hours is as effective as the same dose of vaginal misoprostol with no additional side effects , which provides a convenient alternative for midtrimester pregnancy termination OBJECTIVE The purpose of this study was to compare the clinical efficacy and side effects of 3 doses of intravaginal misoprostol for second-trimester pregnancy termination . STUDY DESIGN This was a prospect i ve r and omized , double-blind controlled clinical trial of 150 women who underwent pregnancy termination between 14 and 30 weeks of gestation . Three intravaginal misoprostol regimens were compared : 200 microg misoprostol at 6-hour intervals ( group 1 ) , 400 microg misoprostol at 6-hour intervals ( group 2 ) , and a loading dose of 600 microg misoprostol followed by 200 microg at 6-hour intervals ( group 3 ) . RESULTS There was a significant difference in the median time to achieve delivery among the 3 groups : group 1 ( 18.2 hours [ IQ , 13.3 - 32.5 hours ] ) vs group 2 ( 15.1 hours [ IQ , 10.9 - 23.7 hours ] ) vs group 3 ( 13.2 hours [ IQ , 11.2 - 21.7 hours ] ; P = .035 ) . Fifty-nine percent of the women in group 1 , 76 % of the women in group 2 , and 80 % of the women in group 3 delivered within 24 hours ( P = .013 ) . There were 7.8 % of the women in group 1 , 0 % of the women in group 2 , and 2 % of the women in group 3 who were undelivered at 48 hours ( P = .02 ) . There was an increase in the incidence of fever in the first 12 hours ( P = .038 ) and in the incidence of vomiting within 3 hours of the initial dose ( P = .048 ) in group 3 compared with the other groups . CONCLUSION Intravaginal misoprostol 400 microg at 6-hour intervals appears to be the preferred regimen for second-trimester pregnancy termination , with a shorter commencement to delivery interval than the 200 microg regimen and fewer maternal side-effects than the 600 microg loading dose regimen OBJECTIVE To compare the efficacy of vaginal and oral misoprostol for the induction of labour in women with intra-uterine foetal death ( IUFD ) . DESIGN A prospect i ve r and omised clinical trial , comparing 200 microg oral and 200 microg vaginal misoprostol , six hourly for a maximum of four doses for the induction of labour in women with IUFD . SETTING Ga-Rankuwa hospital ( Department of Obstetrics and Gynaecology ) , Pretoria , South Africa . It is a tertiary institution serving predominantly black indigenous population . MAIN OUTCOME MEASURES The primary outcome measure was the induction to delivery time , and secondary outcome measures were the number of patients requiring augmentation with oxytocin and all complications were noted . RESULTS Twenty women were r and omised to the vaginal route and 18 to the oral route . The induction to delivery time was shorter with vaginal misoprostol ( 13.5 + /- 8.3 hrs ) compared to oral misoprostol ( 21.4 + /- 13.9 hrs ; p < 0.05 ) . There was no significant difference in the amount of misoprostol needed to achieve successful induction in the two groups . More women ( 10/18 ) who received oral misoprostol required oxytocin augmentation to complete the induction of labour compared with 4/20 women in the vaginal group ( p < 0.05 ; Odds Ratio 2.8 ; 95 % Cl 1.36 - 4.24 ) . There were no cases of failed induction . The systemic side effects ( shivering , diarrhoea , vomiting and pyrexia ) were more common with oral misoprostol ( 44.5 % ) compared to vaginal misoprostol ( 20 % ) . This difference gives an overall Odds Ratio of 2.2 at 95 % Cl of 1.6 - 2.8(p < 0.05 ) . CONCLUSION Vaginal misoprostol achieved successful induction of labour in women with IUFD in a shorter time than oral misoprostol with significantly less side effects Summary Gemeprost ( Cervagem ) has been used widely compared with Misoprostol ( Cytotec ) alone in second trimester pregnancy termination . This prospect i ve r and omised trial was to evaluate the efficacy of intravaginal Misoprostol ( alone ) and Gemeprost in second trimester termination of pregnancy . A total of 54 women with 27 on each arm were involved . A total of 25 patients ( 92.6 % ) in the Misoprostol group and 22 patients ( 81.5 % ) in the Gemeprost group delivered within 48 h. The Misoprostol group delivered earlier , although average number of tablets required were similar . The side-effects were not significant between the two groups in fact , but there was more pyrexia in the Gemeprost group ( p = 0.004 ) . Misoprostol in second trimester termination of pregnancy is clinical ly as effective and less costly than the st and ard regimen of Gemeprost The object of this study was to compare intravaginal misoprostol and dinoprostone ( prostagl and in E2 ) for second-trimester pregnancy termination , and to examine the role of the nitric oxide donor , glyceryl trinitrate , as a possible alternative to prostagl and ins to induce cervical ripening in second-trimester pregnancy termination . This was a r and omised clinical trial . The trial involved pregnant women between 13 and 28 weeks ' gestation admitted with clear medical or obstetric indications for pregnancy termination , and was carried out in the department of obstetrics and gynecology , Assiut University Hospital , Egypt . Patients were classified into Group A , where pregnancy termination was induced by vaginal misoprostol 100 micrograms every 4 hours with a maximum dose of 500 micrograms ; Group B , where induction was by vaginal dinoprostone 6 mg every 6 hours with a maximum dose of 24 mg ; and Group C , where induction involved vaginal glyceryl trinitrate 500 micrograms every 6 hours with a maximum dose of 2.5 mg . Twenty-four hours after the start of induction , the rate of complete abortion in the three groups was 100 % , 66.67 % and 0 % , respectively . The rate of complete abortion was 100 % in the nitric oxide ( glyceryl trinitrate)-induced group after introducing a complementary procedure . The induction – abortion interval was significantly shorter , the number of doses needed was less and the maximum Bishop score reached was greater with misoprostol than with dinoprostone . A higher rate of side effects occurred with the misoprostol-induced group ( 74 % ) compared with the other two groups ( 46.6 % and 0 % ) . Misoprostol is a cheap , effective drug for second-trimester pregnancy termination with short induction abortion intervals but a higher rate of side effects . Prostin E2 is also effective in termination of second-trimester pregnancy but is expensive and may require high doses to be administered . Glyceryl trinitrate is an effective drug for cervical ripening ( softening ) but it has no role in the stimulation of uterine contractions Objective To compare the effectiveness of vaginal misoprostol administered 6 or 12 hourly for second trimester pregnancy termination OBJECTIVE To evaluate the induction-to-abortion time of 3 pharmacokinetic-based protocol s at 13 - 20 weeks of gestation . STUDY DESIGN A r and omized trial was conducted on 153 patients . The oral group ( n = 51 ) received 100 microg misoprostol orally every 2 hours , the vaginal group ( n = 51 ) received 200 microg misoprostol vaginally every 4 hours , and the sublingual group ( n = 51 ) received 100 microg misoprostol sublingually every 2 hours . RESULTS The mean induction-to-delivery time was shorter in the sublingual group ( mean , 651 + /- 507 ) as compared to the vaginal group ( mean , 1,056 + /- 634 , p = 0.01 ) . The number of patients who delivered within 12 hours was significantly higher in the sublingual group ( n = 39 , 78 % ) as compared to the oral ( n = 26 , 52 % ) and vaginal ( n = 20 , 40 % ) groups ( p < 0.001 ) . The numbers of patients who delivered within 24 hours were comparable in the sublingual ( n = 47 , 94 % ) and oral ( n = 46 , 92 % ) groups but higher than in the vaginal group ( n = 39 , 78 % ; p = 0.02 ) . The total misoprostol dose was 543 + /- 422 microg in the sublingual group , 878 + /- 533 microg in the vaginal group and 741 + /- 413 microg in the oral group ( p < 0.001 ) . CONCLUSION A pharmacokinetic-based application of 100 microg of sublingual misoprostol every 4 hours is more effective for induction of second-trimester abortion as compared to 100 microg oral misoprostol every 2 hours and 200 microg vaginal misoprostol every 4 hours Objective : To compare the efficacy of a combined regimen of misoprostol with vaginal misoprostol for early 2nd-trimester pregnancy termination . Methods : This is a prospect i ve study that includes 79 pregnant women who requested legal termination of 2nd-trimester pregnancy between 13 and 22 weeks . Two regimens of misoprostol were used . Group 1 : 400 µg of oral plus 400 µg vaginal misoprostol every 8 h ( combined regimen ) and group 2 : 400 µg of vaginal misoprostol every 3 h up to a maximum of five doses ( vaginal regimen ) . Results : The induction-to-abortion interval was significantly longer in group 1 ( 25.5 ± 24.45 h ) than in group 2 ( 15 ± 7.14 h ) ( p = 0.016 ) . The abortion rate within 24 h in group 1 was of 56.8 vs. 85.7 % in group 2 ( p = 0.006 ) . The hazard rate for vaginal delivery within 24 h was found to be 2.277-fold greater in the group with the combined therapy once controlled for plausible confounders . Conclusions : Our study suggests that oral misoprostol combined with vaginal misoprostol does not reduce the induction-to-abortion interval compared to an exclusively vaginal route when used for early 2nd-trimester pregnancy termination BACKGROUND Intrauterine fetal death is a major problem in obstetrics particularly in developing countries such as Ug and a. Induction of labour in cases of fetal death using the available method of oxytocin is often difficult , expensive and frustrating . OBJECTIVES To compare the effectiveness of vaginal misoprostol and intravenous oxytocin in induction of labour in women with intrauterine fetal death . METHODS One hundred and twenty mothers were allocated in a r and omised controlled way to one of the two induction groups . Oxytocin infusion was titrated based on patient response . The starting dose was 50 mcg ( 1/4 tablet ) in misoprostol group and the dose was doubled every six hours till effective contractions were achieved . The two groups were compared for induction to delivery intervals , costs of the drugs and their safety during induction . RESULTS The success rate within 48 hours of induction was 100 % in the misoprostol group and 96.7 % in oxytocin group . The mean induction to delivery time was significantly longer in the oxytocin group compared with the misoprostol group ( 23.3 versus 12.4 hours ; p= 0.004 ) . In the gestational age before 28 weeks , the induction to delivery interval in oxytocin group , was more than twice that used in misoprostol . However beyond 28 weeks , there was no significant difference . Women with intact membranes had induction to delivery interval of 27.9 hours in the oxytocin group and 14.7 hours in the misoprostol group ( p=0.002 ) . When the membranes were ruptured , the values were 10.5 and 8.5 hours respectively ( p=0.6 ) . The induction to delivery time in cases with Bishop 's score < 6 was 29.8 hours in the oxytocin group and 15.9 hours in misoprostol group ( p=0.001 ) . The corresponding values for Bishop 's scores > 6 were 10 and 7.9 hours respectively ( p=0.6 ) . The majority of patients in misoprostol group ( 62 % ) , required less than one tablet for successful induction . Misoprostol was cheaper ( 0.65 US dollars than oxytocin ( 7.86 US dollars ) Retained placenta occurred in only 3.3 % of the patients in the misoprostol group . There were no cases of ruptured uterus in both groups . CONCLUSION Intravaginal misoprostol is more effective and cheaper than intravenous oxytocin for inducing labour in patients with intrauterine fetal death Misoprostol a synthetic prostagl and in E/1 analog widely prescribed for the prevention and treatment of peptic ulcer has become an important drug in obstetrics and gynecology . We have recently reported its ability to bring about cervical changes uterine contractions and successful induction of labor at term . Misoprostol has also been found to be effective in inducing abortion and therefore offers an effective alternative to the available medical and surgical options in second-trimester abortion . Because of the different pharmacokinetics when given orally or vaginally the optimum dosage and route of administration have not been definitively determined w4x . We performed a prospect i ve r and omized-controlled clinical trial at Wad Medeni Teaching Hospital to compare the efficacy of oral misoprostol with that of vaginal misoprostol for pregnancy termination in cases of intrauterine fetal demise in the second trimester . ( excerpt A prospect i ve r and omised controlled trial was undertaken to compare the efficacy of two routes of administration , oral versus vaginal , of the prostagl and in El analogue misoprostol ( Cytotec ) to effect termination of pregnancy in the mid‐trimester Objective To test the feasibility of mounting a r and omised controlled trial comparing mifepristone – misoprostol versus dilation and evacuation ( D&E ) for midtrimester abortion A r and omised controlled trial was conducted to compare the relative efficacies of two regimens : Misoprostol given only vaginally or orally followed by vaginal administration of the same drug , for second trimester abortion . Multiparous women with a pregnancy of 16 to 20 weeks with no contra-indications to the drug were selected . They were r and omly allocated into two groups . Patients in the first group , the ' only vaginal misoprostol ' group ( n = 30 ) , were given misoprostol 400 microg 6 hourly only through vaginal route up to a maximum of 4 such doses . Women in the other group , the ' oral plus vaginal misoprostol ' group ( n = 24 ) , received 400 microg of the drug at intervals of 12 hours for 2 doses , followed by 400 microg 6 hourly per vaginum up to a maximum of 4 such . Ten units of oxytocin was started in all cases when os was 4 cm dilated . Complete expulsion was 83.33 % with an average time of 13.28 hours in the only vaginal misoprostol group . Complete expulsion occurred in 87.5 % of women receiving oral followed by vaginal misoprostol with an average time of 8.93 + /- 0.01 hours from the first vaginal dose ( p<0.05 ) . More importantly , 66.67 % women in second group delivered within 10 hours of the vaginal dose . Complete expulsion was defined in those cases where no check curettage was needed . Side-effects were not significant . This implies that misoprostol given by the vaginal route following oral priming doses had a higher success rate and a potential for a reduced hospital stay and higher bed turn-over rate Summary : This prospect i ve , r and omized study compared the efficacy of intravaginal misoprostol ( Cytotec ) and gemeprost ( Cervagem ) as an abortifaeient for intrauterine deaths in second trimester pregnancy . Side‐effects , complications and the cost‐effectiveness associated with each drug were assessed . 21 out of 25 patients ( 84 % ) in the misoprostol group aborted whereas only 17 out of 25 patients ( 68 % ) in die gemeprost group aborted within 24 hours after the initiation of therapy . In the misoprostol group , the abortion rate was influenced by the gestational age with 100 % abortion rate for those > 17 weeks ' gestation compared to 67 % for those with a gestational age of 13–16 weeks . Side‐effects were rare in either group and no major complications were reported in either group . Misoprostol was definitely more cost‐effective compared to gemeprost as the mean cost of inducing an abortion using misoprostol was RM 1.08 whereas that of gemeprost was RM 105 . We thus concluded that misoprostol was at least as effective as gemeprost as an abortifacient for intrauterine death in second trimester pregnancy . Moreover , it was less costly , with very few side‐effects Objectives To compare the efficacy of repeated doses of 100 μg vs. 200 μg misoprostol given sublingually for induction of second trimester abortion . Methods One hundred and sixty-two women at 15–22 weeks ' gestation were r and omized to receive every 2 h either 100 μg ( group 1 ; n = 81 ) or 200 μg ( group 2 ; n = 81 ) misoprostol sublingually . The primary outcome measure was the abortion rate within 24 h. The secondary outcome measures were the induction-abortion interval , the total misoprostol dose required , and side effects of the regimen . Results There was no significant difference between the two groups with regard to the abortion rates within 12 h ( 43.2 % in group 1 vs. 48.1 % in group 2 ; p = 0.52 ; relative risk [ RR ] : 0.81 ; 95 % confidence interval [ CI ] : 0.4–1.5 ) and 24 h ( 92.6 % in group 1 vs. 91.4 % in group 2 ; p = 0.77 ; RR : 1.11 ; 95 % CI : 0.37–3.6 ) . The induction-abortion intervals in the two groups were of similar length ( 885 minutes in group 1 vs. 912 minutes in group 2 ; p = 0.72 ) . When the total dose of misoprostol was compared between the two groups , women belonging to group 2 on average had received significantly more misoprostol than those in group 1 ( 1274 ± 592 μg [ 7 ± 3 doses ] vs. 614 ± 432 μg [ 6 ± 4 doses ] , respectively ; p = 0.000 ) . Conclusions Sublingual administration of repeated doses of 100 μg misoprostol for abortion induction appears to be equally effective to that of repeated doses of 200 μg OBJECTIVE To compare the efficacy of oral misoprostol with that of intra-amniotic prostagl and in F2alpha ( PGF2alpha ) for second trimester pregnancy termination . METHODS One hundred seventeen women with pregnancies of between 16 and 22 weeks ' gestation were r and omly assigned after insertion of laminaria to receive either oral misoprostol 400 microg every 4 hours ( to a maximum of four doses ) or intra-amniotic PGF2alpha 40 mg . The rate of complete abortion within 24 hours was the primary outcome for power analysis . Secondary outcome measures were the rate of dilatation and curettage ( D&C ) for retained placenta and the rates of fever and gastrointestinal complications . RESULTS Patient characteristics were similar in both groups . The rate of complete abortion within 24 hours was similar in the misoprostol ( 63 % ) and PGF2alpha ( 66 % ) groups . The rate of retained placenta requiring D&C was significantly greater in the PGF2alpha group ( 22.4 % vs. 3.4 % , P = 0.002 ) . There were no differences in other maternal morbidities . Parous patients treated with oral misoprostol had a significantly greater rate of complete abortion than nulliparous patients ( 84 % vs. 57 % , P = 0.04 ) . CONCLUSIONS Oral misoprostol is as effective as intra-amniotic PGF2alpha for second trimester pregnancy termination when laminaria is inserted before treatment . Parous patients have a higher success rate than nulliparous patients with use of oral misoprostol . Oral misoprostol is associated with a very low rate of placental retention OBJECTIVE Our purpose was to compare the efficacy of oral misoprostol with that of vaginal misoprostol for midtrimester termination of pregnancy . STUDY DESIGN Women seen for midtrimester pregnancy termination were r and omly assigned to receive either misoprostol orally in a dose of 200 microg every hour for 3 hours followed by 400 microg every 4 hours or vaginally in a dose of 400 microg every 4 hours . The protocol was followed for 24 hours , after which time further management was at the discretion of the attending physician . The primary outcome measure was the induction-to-delivery interval . Sample size was calculated a priori . Statistical analysis was performed with the t test for continuous variables and the chi(2 ) test for categorical variables . P < .05 was considered significant . RESULTS One hundred fourteen women were r and omized , with 49 receiving vaginal misoprostol and 65 receiving oral misoprostol . The two groups were comparable with respect to maternal age , parity , indication for pregnancy termination , gestational age , and maternal weight . The mean induction-to-delivery interval was significantly shorter for the vaginal group ( 19.6 + /- 17.5 hours vs 34.5 + /- 28.2 hours , P < .01 ) . Length of stay was also shorter in the vaginal group ( 32.3 + /- 17.3 hours vs 50.9 + /- 27.9 hours , P < .01 ) . Significantly more patients in the vaginal group were delivered within 24 hours ( 85.1 % vs 39.5 % , P < .01 ) , and more patients in the oral group required changes in the method of induction when they were undelivered after 24 hours ( 38.2 % vs 7 % , P < .01 ) . The only complication was an increase in febrile morbidity in the vaginal group ( 25 % vs 6.7 % , P = .046 ) . This did not result in an increased use of antibiotics , and all the fevers resolved post partum without further complications . CONCLUSIONS Vaginal administration of misoprostol result ed in a shorter induction-to-delivery interval . The shorter length of stay should result in improved patient care The combination of mifepristone ( RU486 ) and prostagl and in is effective in the induction of abortion in the second trimester . The optimal regimen is still under development , but is likely to be characterized by a short induction-to-abortion interval , low incidence of side-effects and high acceptability . We have investigated further whether misoprostol , a synthetic prostagl and in E1 analogue , can reliably induce second trimester abortion in 70 women pre-treated with mifepristone , and whether different routes of administration affect the induction-to-abortion interval . Abortion was achieved in 97 % [ 95 % confidence interval ( CI ) 90 - 100 % ] of cases without resort to other prostagl and in agents . The mean induction abortion time for the studied population was 6.4 h ( 95 % CI 5.6 - 7.0 h ) . No significant difference was found between two different routes of administration , namely vaginal versus a combination of vaginal and oral . Misoprostol has a number of advantages over other prostagl and in preparations . We recommend that , following pre-treatment with mifepristone , misoprostol is used as the prostagl and in of choice to induce abortion in the second trimester OBJECTIVE : To compare the effectiveness and side effects of oral and vaginal misoprostol for the termination of second and third trimester pregnancy with intrauterine fetal death . METHODS : Eighty pregnant women at 16‐41 weeks ' gestation with intrauterine fetal death were r and omized in two groups to receive either 400 & mgr;g of misoprostol orally every 4 hours ( n = 40 ) or 200 & mgr;g of misoprostol vaginally every 12 hours ( n = 40 ) until the termination of pregnancy was completed . The adverse effects , progress , and outcomes of delivery were assessed . RESULTS : The groups were similar in age , weight , height , gestational age , parity , and modified Bishop scores before intervention . The mean induction‐to‐delivery time in the oral group ( 13.95 [ st and ard deviation ( SD ) = 5.63 ] hours ) was significantly shorter than the time in the vaginal group ( 18.87 [ SD = 10.38 ] hours , P = .001 ) . The number of deliveries within 24 hours after the initial drug administration in the oral group ( 92.5 % ) was significantly higher than the number in the vaginal group ( 67.5 % , P < .001 ) , and all delivered within 48 hours after the initial drug administration . However , the gastrointestinal side effects in the oral group was significantly higher than in the vaginal group ( P = .005 ) . CONCLUSION : Misoprostol ( 400 & mgr;g given orally every 4 hours ) was more effective than misoprostol ( 200 & mgr;g given vaginally every 12 hours ) for the termination of second and third trimester pregnancy with intrauterine fetal death , but with more gastrointestinal side effects . ( Obstet Gynecol 2003;101:70‐73 . © 2003 by The American College of Obstetricians and Gynecologists . Objective . To compare two methods for second trimester termination of pregnancy : mifepristone and misoprostol versus Dilapan ® and sulprostone . Methods . This was a r and omized study involving 16 patients with a singleton live fetus with congenital malformations or genetic disorders . Eight patients were treated with 200 mg mifepristone orally followed by 200 μg misoprostol vaginally 3 hourly and eight patients received a sulprostone infusion after cervical dilatation with Dilapan . Results . Mifepristone and misoprostol had a mean induction interval of 17.8 hours and sulprostone and Dilapan 20.9 hours . The mean induction interval did not differ significantly . Mean hospital stay was shorter in the patients treated with misoprostol : 2.1 vs. 3.3 days ( p = 0.02 ) with a 95 % confidence interval of −2.1 to 0.3 . Conclusion . Mifepristone and misoprostol did not reduce the induction interval significantly compared to the sulprostone and Dilapan treatment for second trimester pregnancy termination . Hospital admission was significantly shorter in patients treated with mifepristone and misoprostol OBJECTIVE To compare the clinical efficacy and side effects of oral misoprostol with vaginal misoprostol for second-trimester pregnancy termination . METHODS A r and omized clinical trial of medical pregnancy termination between 14 and 26 weeks ' gestation was conducted . Three misoprostol regimens were compared : 400 μg vaginally at 6-hour intervals ( group 1 ) , 400 μg orally at 3-hour intervals ( group 2 ) , and a loading dose of 600 μg vaginally followed by 200 μg orally at 3-hour intervals ( group 3 ) . A sample size of 225 women was required for equivalence of the three regimens , with an interim safety analysis planned at 80 women . RESULTS A significant difference between the groups was evident at the interim safety analysis and the study ceased . The subset of 84 women recruited before the study closure is described . There was a significant difference in the median time to achieve delivery among the three groups : group 1 , 14.5 hours ( 95 % confidence interval 12.0 , 16.9 ) , versus group 2 , 25.5 hours ( 13.5 , 23.8 ) , versus group 3 , 16.4 hours ( interquartile range 14.2–37.3 ) ( P = .042 ) . Within 24 hours of commencement 85.7 % of women in group 1 , 44.8 % in group 2 , and 74.1 % in group 3 delivered ( P = .003 ) . At 48 hours 0 % in group 1 , 20.7 % in group 2 , and 3.7 % in group 3 were undelivered ( P = .011 ) . There was no difference in women 's perceptions of the termination process . CONCLUSION In second-trimester pregnancy termination , a vaginal misoprostol regimen of 400 μg every 6 hours was 1.9 times more likely to result in delivery within 24 hours from commencement than an oral regimen of 400 μg every 3 hours OBJECTIVE To examine the efficacy of vaginal misoprostol for mid-trimester pregnancy termination . METHODS This r and omized trial compared misoprostol , 200 microg per vaginum q 12 h to a protocol of concentrated oxytocin plus low-dose vaginal prostagl and in E2 suppositories ( 10 mg q 6 h ) . Success was defined as an induction-to-delivery interval < or = 24 h. RESULTS Interim analysis of the first 30 ( 15-misoprostol , 15-concentrated oxytocin ) women demonstrated that the 2 groups were similar with regard to indication for delivery , gestational age , and demographic characteristics . Misoprostol was associated with a lower success rate ( 67 vs. 87 % , P = .2 ) , a longer induction-delivery interval ( 22 h vs. 18 h , P = .09 ) , a higher rate of retained placenta requiring curettage ( 27 vs. 13 % , P = .65 ) , and a higher live birth rate ( 50 vs. 0 % , P = .006 ) . CONCLUSIONS Compared to a regimen of concentrated oxytocin plus low-dose prostagl and in E2 , misoprostol administered as vaginal tablets in a dose of 200 microg q 12 h is not satisfactory for mid-trimester pregnancy termination in an unselected population OBJECTIVE Our purpose was to compare the effectiveness , women 's views of the termination procedure , and success of umbilical cord culture for vaginal and oral misoprostol versus intra-amniotic prostagl and in PGF(2alpha ) for second-trimester pregnancy termination ( STPT ) . STUDY DESIGN We r and omized 217 women , 15 to 24 weeks ' gestation , into 3 groups . Oral ( OM ) and vaginal ( VM ) misoprostol groups received 400 microg of misoprostol every 4 hours for 24 hours . The intra-amniotic PGF(2alpha ) ( IAPG ) group received 40 mg of PGF(2alpha ) followed by oxytocin infusion . Women completed self-administered question naires 3 weeks after the termination procedure . Umbilical cord sample s were collected at delivery for karyotype analysis . The primary outcome was the time from start of the procedure to placental delivery . Secondary outcomes were maternal complications , women 's acceptance of the termination procedure , and success rates of umbilical cord culture . RESULTS The time was longer for the OM group ( 30.5+/-14.4 hours ) compared with the VM group ( 18.3+/-8.2 hours ) and the IAPG group ( 21.1+/-10.2 hours ) , P<.001 for both comparisons . Women in the VM group reported being more willing to repeat the termination method in the future and reported fewer side effects than those in the other groups , P<.001 . Failure rates for umbilical cord cultures were 9.6 % , 17.0 % , and 45.6 % for the VM , OM , and IAPG groups , respectively . CONCLUSION Oral misoprostol is less effective than intra-amniotic PGF(2alpha ) or vaginal misoprostol for STPT . Women report vaginal misoprostol more acceptable than other methods . Umbilical cord culture failure rate is highest in the IAPG group Misoprostol is one of the most popular products used for pregnancy termination because of its high efficacy , low cost and stability at room temperature . It was found that a dosage of 400 mcg of intravaginal misoprostol is optimal for secondtrimester termination [ 1–3 ] ; however , the optimal time interval between doses has not been established . We conducted this study to compare the efficacy of intravaginal misoprostol , 400 mcg , administered every 3 and 6 h. Pregnant women with live fetus and unfavorable cervix at accurate gestational age of 14–28 weeks with indications for pregnancy termination were allocated into either group of 3-h interval or 6-h interval by block r and omization . A Bishop score was obtained for cervical assessment just before initiating misoprostol . Exclusion Objective To compare the abortifacient efficacies of two intravaginally administered misoprostol doses and gemeprost in termination of second-trimester pregnancy . Methods Eighty-one women between 12 and 24 weeks ' gestation requesting abortion were r and omized to receive intravaginally either 100 μg of misoprostol at 6-hour intervals ( n = 27 ) , 200 μg of misoprostol at 12-hour intervals ( n = 26 ) , or 1.0 mg of gemeprost at 3-hour intervals ( n = 28 ) . The regimen was continued until abortion , or for 36 hours , with assessment of the rate of complete and incomplete abortions as well as side effects within 48 hours from the start of the treatment . Results The final rates of terminations were 74 % in the 100 μg misoprostol group , 92 % in the 200-μg misoprostol group , and 89 % in the gemeprost group . Abortion was complete in 37 % , 61 % and 32 % in each group , respectively ( P = .03 , when the 200-μg misoprostol group was compared with the two other groups ) . The inductions- to-abortion interval was longer ( P = .001 ) in he misoprostol groups ( mean 23.1 hours for the 100-μg and 27.8 hours for the 200-μg dose ) than in the gemeprost group ( 14.5 hours ) . There was less pain ( P = .01 ) , and vomiting ( P = .01 ) in the misoprostol groups that in the gemeprost group . The mean blood loss in the misoprostol groups was lower than in the gemeprost group ( P = .001 ) . Conclusion Intravaginal application of 200 μg of misoprostol at 12-hour intervals in induction of second-trimester abortion is equally effective to a st and ard gemeprost regimen . Misoprostol causes fewer side effects and is cheaper and more practical to use A prospect i ve r and omized , double-blind , controlled clinical trial to compare the clinical efficacy and side effects of intravaginal misoprostol with the traditional prostagl and in , gemeprost , in second-trimester pregnancy interruption was conducted . A sample size of 100 women was calculated to demonstrate that misoprostol was as effective as gemeprost in achieving delivery within 24 hours ( alpha = 0.1 , 80 % power ) . Women were recruited with fetal death in utero , severe fetal anomaly , or psychosocial pregnancy termination between 14 and 28 weeks gestation and r and omized to receive either 1 mg gemeprost 3 hourly for 5 doses , or 200 mcg misoprostol 6 hourly for 4 doses , intravaginally . The therapeutic regimens were repeated if undelivered by 24 hours . Those undelivered after 48 hours received an extra-amniotic PGF2 alpha infusion . The median gestation at recruitment was identical : gemeprost 19 weeks ( IQ 17 - 22 weeks ) vs. misoprostol 19 weeks ( IQ 17 - 21 weeks ) , P = 0.887 . Delivery within 24 hours occurred in 75.1 % of women receiving gemeprost and 74.9 % receiving misoprostol ( P = 1.0 ) . The median time from prostagl and in commencement to delivery was similar : gemeprost 13.7 hours ( IQ 9.0 - 23.5 hours ) vs. misoprostol 16.9 hours ( IQ 10.3 - 23.5 hours ) , P = 0.769 . A significant reduction in the incidence of vomiting in women r and omized to misoprostol occurred ( 34 % vs. 13.2 % , P = 0.017 ) . There was no significant difference in the incidence of maternal fever > 37.5 degrees C , nausea , diarrhea , or placental retention . A 200-fold pharmaceutical cost advantage was observed with the use of misoprostol compared with gemeprost . Intravaginal misoprostol performs as effectively as gemeprost in achieving delivery in the second trimester without increase in adverse effects and displaying a significant cost advantage OBJECTIVE To compare repeated doses of sublingual with oral misoprostol in the medical management of early pregnancy failure . MATERIAL AND METHOD One hundred and thirty eight women with a period of gestation less than 20 week calculated by her last menstrual period and less than 12 weeks by size were sequentially allocated to two groups to receive either 400 microg of misoprostol orally or sublingually every 4 hours until termination of pregnancy was completed . RESULTS There is no difference in the mean induction to abortion interval . Fever and chill were more common in sublingual group compared with oral group . The other adverse effects were similar and included nausea , vomiting , diarrhea , abdominal pain , and headache . CONCLUSION Sublingual misoprostol is as effective as oral route . Most adverse effects are similar in both groups except fever was more common in sublingual group OBJECTIVE : To compare the efficacy , side effects , and complications of high-dose vaginal misoprostol with concentrated intravenous oxytocin plus low-dose vaginal prostagl and in ( PGE2 ) for second-trimester labor induction . METHODS : One hundred twenty-six consenting women with maternal or fetal indications for pregnancy termination and no prior cesarean delivery were r and omly assigned to receive either vaginal misoprostol 600 μg 1 × , 400 μg every 4 hours 5 × ( misoprostol group , n = 60 ) or escalating-dose concentrated oxytocin infusions ( 277–1,667 mU/min ) plus vaginal PGE2 10 mg every 6 hours 4 × ( oxytocin group , n = 66 ) . Both groups received concurrent extra-amniotic saline infusion for cervical ripening . Women who failed their assigned regimen received 20 mg of PGE2 suppositories every 4 hours until delivery . Analysis was by intent to treat . RESULTS : Demographic characteristics were similar between study groups . Median induction-to-delivery interval was significantly shorter in the misoprostol group ( 12 hours ) than in the oxytocin group ( 17 hours ; P < .001 ) . There was a higher induction success rate at 24 hours in the misoprostol group ( 95 % ) than in the oxytocin group ( 85 % ; P = .06 ) , although this difference did not reach statistical significance . The incidence of live birth ( 25 % versus 17 % ) , chorioamnionitis ( 5 % versus 2 % ) , and postpartum hemorrhage greater than 500 mL ( 3 % versus 3 % ) were similar between the misoprostol and oxytocin groups , respectively . Diarrhea ( 2 % versus 11 % ; P = .04 ) , nausea/emesis ( 25 % versus 42 % ; P = .04 ) , and retained placenta requiring curettage ( 2 % versus 15 % ; P = .008 ) were significantly less common in the misoprostol group when compared with the oxytocin group , respectively . Isolated intrapartum fever , however , was more frequent in the misoprostol group ( 67 % ) than in the oxytocin group ( 21 % ; P < .001 ) . CONCLUSION : Compared with concentrated oxytocin plus low-dose vaginal PGE2 , high-dose vaginal misoprostol is associated with significantly shorter induction-to-delivery intervals , fewer side effects , a lower incidence of retained placenta , and comparable incidence of live birth . LEVEL OF EVIDENCE : OBJECTIVE Our purpose was to compare the efficacy , safety , and adverse effects of intra-amniotically administered (15S)-15-methyl-prostagl and in F(2alpha ) and intravaginally administered misoprostol for second-trimester uterine evacuation . STUDY DESIGN Fifty-one patients were r and omly assigned to receive either a single 2.5-mg intra-amniotic injection of (15S)-15-methyl-prostagl and in F(2)(alpha ) ( n = 26 ) or two 200-microg intravaginal doses of misoprostol ( n = 25 ) at 12-hour intervals . The primary outcome measured was evacuation of the uterus within 24 hours . RESULTS The mean time from initiation of termination to uterine evacuation was less in the prostagl and in group than in the misoprostol group ( 17.5 + /- 8.6 hours vs 22.3 + /- 12.5 hours ) , but this was not statistically significant ( P > .05 ) . The rate of successful fetal evacuation at 24 hours was significantly higher in the prostagl and in group than in the misoprostol group ( 88 % vs 60 % , P = .02 ) . The complete-abortion rate and the incidence of adverse effects were similar in both groups . CONCLUSION The use of an intra-amniotic injection of (15S)-15-methyl-prostagl and in F(2alpha ) for midtrimester pregnancy termination is safe and is associated with a greater number of successful uterine evacuations within 24 hours , without an increase in adverse effects , than intravaginal administration of misoprostol OBJECTIVE To study the effectiveness of single application of intravaginal misoprostol versus intracervical prostagl and in E2 gel for ripening the unfavorable cervix and labor induction . METHOD One hundred and ten patients with indications for induction of labor with unfavorable cervices were r and omized to receive either 100 microgram tablets of misoprostol placed in the posterior vaginal fornix or prostagl and in E2 1.5 mg in gel placed into the endocervix . Those , who were not in active labor after 24 hours , had labor induced with amniotomy and oxytocin . RESULTS Among 110 patients recruited , 60 received misoprostol and 50 received prostagl and in E2 gel . The average interval from start of induction to vaginal delivery was 19.14 + /- 10.64 hours in misoprostol group and 21.37 + /- 13.09 hours in the prostagl and in E2 group ( p = 0.33 ) . Five patients ( 8 % ) in the misoprostol group had induction of labor after 24 hours of the treatment compared with 13 patients ( 26 % ) in the PGE2 group . The difference was significant ( p = 0.03 ) . Oxytocin augmentation was 35 % in the misoprostol group and 34 % in the prostagl and in E2 group ( p = 0.86 ) . There were no significant differences between routes of delivery . Nineteen patients ( 31 % ) in misoprostol group and 16 patients ( 32 % ) in the PGE2 gel group had cesarean deliveries . There was one case ( 1.7 % ) of uterine hyperstimulation in the misoprostol group and none in the PGE2 gel group . There were no significant difference in Apgar scores < 7 at 1 and 5 minutes , or admission to the neonatal intensive care unit between the 2 groups . CONCLUSION Vaginal misoprostol is an effective agent for cervical ripening and induction of labor . Complications associated with prostagl and in administration were not statistically different between the 2 groups , but hyperstimulation occurred more in misoprostol group BACKGROUND To compare the efficacy and side effects of extra-amniotic prostagl and in F2alpha with intracervical misoprostol for midtrimester termination of pregnancy METHODS Forty women were r and omized to receive either intracervical misoprostol or extra-amniotic prostagl and in F2alpha for termination of pregnancy for congenital abnormalities or intrauterine fetal death . Induction-abortion interval and the incidence of side effects were analyzed for both groups . RESULTS All women in the PGF2alpha group ; aborted within 28 hours , 16 ( 80 % ) of which aborted within 20 hours . Medical termination of pregnancy was complete in 13 cases ( 65 % ) . In the misoprostol group ; all women aborted within 20 hours , 18 ( 90 % ) of which aborted within 13 hours . Medical termination of pregnancy was complete in 17 cases ( 85 % ) . The induction to abortion intervals for the extra-amniotic PGF2alpha and intracervical misoprostol were 16+/-5.9 hours , and 10.3+/-4 hours ( mean+/-s.d . ) respectively . This was statistically significant ( p=0.001 ) . The incidence of prostagl and in-associated pyrexia , vomiting and diarrhea were significantly increased in the PGF2alpha group ( p<0.05 ) . Abdominal pain was similar in both groups . There was no post-abortive hemorrhage or infection . CONCLUSIONS Misoprostol is an effective , easy to use , safe and cheap drug for termination of second trimester pregnancy . Intracervical administration of misoprostol appears to be effective and well-tolerated with less side effects and no complications . Larger , r and omized comparative studies should be carried out to assess its potential advantages The purpose of this study was to compare the efficacy and side effects of two different misoprostol regimens for second-trimester pregnancy termination . Sixty women in second trimester of gestation with indications for pregnancy termination were r and omly assigned in two equal groups to receive either vaginal or oral misoprostol . The dosing regimen was 400 microg as the initial dose followed by 400 microg up to 3 doses ( 1200 microg ) if needed in each group . Efficacy and side effects were compared . The percentage of women who delivered was significantly higher in vaginal group than the oral group ( 86.7 vs. 43.3 p = 0.0006 ) . No significant differences in complication rates and induction to delivery interval were noted between the two groups . Vaginal administration of misoprostol result ed in a higher success rate for second trimester pregnancy termination , whereas , no significant differences in induction to delivery time and complication rates were noted between vaginal and oral groups BACKGROUND The most widely used medical method of terminating second-trimester pregnancy is the intravaginal administration of prostagl and in E2 ( dinoprostone [ PGE2 ] ) . This treatment is highly effective but is associated with severe gastrointestinal side effects and hyperpyrexia . METHODS We conducted a prospect i ve , r and omized trial comparing the efficacy and safety of misoprostol , a prostagl and in E1 analogue ( 200 micrograms intravaginally every 12 hours ) , with the efficacy and safety of PGE2 ( 20 mg intravaginally every 3 hours ) . The study population included 55 pregnant women between 12 and 22 weeks ' gestation who were undergoing termination of pregnancy for either intrauterine fetal death ( 37 women ) or medical or genetic reasons ( 18 women ) . RESULTS The rate of successful abortions within 24 hours was 81 percent ( 22 of 27 women ) with PGE2 and 89 percent ( 25 of 28 women ) with misoprostol ( P = 0.47 ) . All the women who received misoprostol had successful abortions within 38 hours . Among those who had an abortion within 24 hours , the mean interval from treatment to abortion was similar in both groups ( 10.6 hours with PGE2 and 12.0 hours with misoprostol , P = 0.33 ) . The rate of complete abortion , defined as the passage of the fetus and the placenta simultaneously , was 32 percent for PGE2 and 43 percent for misoprostol ( P = 0.56 ) . Certain side effects were more frequent in the women receiving PGE2 than in those receiving misoprostol : pyrexia ( 63 percent vs. 11 percent ; P < 0.001 ) , uterine pain ( 67 percent vs. 57 percent , P = 0.58 ) , vomiting ( 33 percent vs. 4 percent , P = 0.005 ) , and diarrhea ( 30 percent vs. 4 percent , P = 0.012 ) . The average cost per treatment was $ 315.30 for PGE2 , as compared with $ 0.97 for misoprostol . CONCLUSIONS Misoprostol is at least as effective as PGE2 for the termination of second-trimester pregnancy involving either a dead or a living fetus , but it is less costly , is easier to administer , and is associated with fewer adverse effects We evaluated the efficacy of initiating a second trimester medical abortion outside of a health care facility using patient self-administered serial intravaginal misoprostol . Patients scheduled for second trimester medical termination of pregnancy were r and omized to an inpatient or outpatient group . Both groups received a single 200-microg vaginal misoprostol tablet every 6 h. No other abortifacients were used . The home group self-administered the misoprostol and returned to the hospital for clinical reasons or after 24 h and again at 48 h. Forty-two women were assigned to the inpatient and 45 to the outpatient groups . There was no difference between the groups in demographics or indications for terminations . The median hours from first misoprostol to delivery of the fetus was 12 and 14 ( inpatient versus outpatient , respectively ; p = 0.28 ) . The total median hours in hospital were 24 versus 11 ( inpatient versus outpatient , respectively ; p < 0.05 ) . Two patients ( 4 % ) in the outpatient group delivered the fetus outside of the hospital . There were no cases of hemorrhage in either group . Outpatient initiation of second trimester medical termination with self-administered misoprostol is effective and decreases time of hospitalization OBJECTIVE To compare the effectiveness of misoprostol administrated intravaginally alone versus misoprostol with oxytocin infusion for termination of pregnancy at 13 to 29 weeks . Subjects and methods . Ninety women at 13 - 29 weeks requesting pregnancy termination were r and omized to receive 200 microgram of misoprotol intravaginally every 12 hours either with oxytocin infusion or alone for up to 48 hours . RESULTS The mean induction to abortion interval was significantly shorter in the misoprostol-oxytocin group than in the misoprostol alone group ( 22+/-10.8 hours versus 27+/-14.1 hours respectively p<0.05 ) . The 48 hours successful abortion rates were 95 % and 90 % respectively . Abortion was complete in 79.1 % and 62.5 % respectively . Side effects were similar between groups . CONCLUSION Vaginal misoprostol associated with oxytocin infusion is more effective than misoprostol alone in termination of second-trimester pregnancy Extra-amniotic prostagl and in F2α ( PG F2α ) is probably the most widely used medical method for mid-trimester termination of pregnancy . The method is highly effective but is financially costly , particularly for poor countries faced with restricted health budgets . The aim of this study was to establish whether misoprostol administered vaginally is as effective as PG F2α . Sixty-one patients were prospect ively r and omized to receive either misoprostol ( n=30 ) vaginally , or PG F2α ( n=31 ) extra-amniotically . The overall success rate was 83.6 % . The success rates in the misoprostol and PG F2α groups were 83.3 % and 83.8 % respectively . There was no statistical difference in the groups in relation to side effects . In this carefully selected group of patients , misoprostol was as safe and effective as PG F2α in mid-trimester termination of pregnancy . In these days of financial constraints , misoprostol is the preferred method for mid-trimester termination of pregnancy OBJECTIVE To compare the effectiveness of misoprostol administered intravaginally every 6 versus every 12 hours for termination of second-trimester pregnancies . METHODS One hundred pregnant women at 12 - 22 weeks ' gestation were r and omized to receive 200 microg of misoprostol intravaginally either every 6 or every 12 hours for up to 48 hours . RESULTS The incidences of abortion within 48 hours after initial drug administration were 87.2 and 89.2 % , the complete abortion rates 43.9 and 33.3 % , and the mean abortion intervals 13.8 and 14.0 hours in the 6- and 12-hour groups , respectively . Side effects were similar between groups . CONCLUSION Misoprostol administered vaginally is effective for terminating second-trimester pregnancies . Shortening the dosing interval from 12 to 6 hours produced no significant benefit OBJECTIVE Our purpose was to determine whether intracervical placement of laminaria tents would improve the effectiveness of the prostagl and in analog misoprostol for the elective termination of pregnancies in the second trimester . STUDY DESIGN Sixty-eight women between 12 and 22 weeks of gestation with either an intrauterine fetal death ( n = 40 ) or medical or genetic indications for pregnancy termination ( n = 30 ) were r and omized to receive 200 micrograms of misoprostol administered vaginally every 12 hours with or without intracervical placement of laminaria concurrently with the first dose of misoprostol . RESULTS The rate of abortion 24 hours after initiation of treatment was 69.7 % in the 33 women receiving misoprostol alone and 68.6 % in the 35 women treated with misoprostol and laminaria . The abortion rates 48 hours after initiation of treatment were 84.8 % and 91.4 % , respectively , an insignificant difference . The complete abortion rate was also similar between women receiving misoprostol alone ( 39.3 % ) and the group receiving misoprostol and laminaria ( 37.5 % ) . There were no significant differences in the incidence of fever , vomiting , diarrhea , or pain . The mean interval from initiation of treatment to abortion was also similar , 15.7 hours in those receiving misoprostol alone and 17.4 hours in those treated with misoprostol and laminaria . In both groups women who had live fetuses at the start of the procedure had a higher failure rate of abortion and a longer time interval to abortion than women whose fetus was dead . CONCLUSIONS Laminaria tents inserted concurrently with the first dose of misoprostol do not significantly improve the abortifacient effect of vaginal misoprostol in the second trimester of pregnancy OBJECTIVE The purpose of this study was to compare the efficacy and adverse effects of vaginal misoprostol and intra-amniotic PGF2alpha for midtrimester abortion . STUDY DESIGN One hundred thirty-two women between 12 and 24 weeks ' gestation , seeking abortion in a tertiary hospital , were r and omized to receive vaginal misoprostol ( 400 microg every 3 hours ) or intra-amniotic PGF2alpha ( carboprost 1.5 mg ) . Main outcome measures were induction-to-abortion interval , success rates at 24 and 48 hours , and adverse effects . RESULTS Successful abortion rates at 24 and 48 hours between intra-amniotic PGF2alpha and vaginal misoprostol were not statistically different . However , vaginal misoprostol results in a significantly shorter mean induction-to-abortion interval , compared with intra-amniotic PGF2alpha ( misoprostol : 16.2 hours ; intra-amniotic PGF2alpha : 20.8 hours ; P = .006 ) , particularly among multiparous women ( misoprostol : 13.1 hours ; intra-amniotic PGF2alpha 18.3 hours ; P = .011 ) and for gestation below 130 days ( misoprostol : 14.6 hours ; intra-amniotic PGF2alpha : 20.2 hours ; P = .015 ) . Fever and shivering were commoner with vaginal misoprostol . CONCLUSION Vaginal misoprostol should be the regimen of choice for midtrimester abortion , particularly for multiparous women and women in the early second trimester OBJECTIVE To compare the efficacy of methods for second trimester pregnancy termination . METHODS A prospect i ve r and omized study of women undergoing pregnancy termination between 14 and 28 weeks gestation . Three hundred and forty patients with poor cervical condition ( Bishop score < or = 4 ) in whom one of five termination methods were used were assessed : ( i ) extraamniotic administration of ethacridine lactate ( 82 patients ) ; ( ii ) intracervical prostagl and in ( PG ) E2 gel ( 100 patients ) ; ( iii ) intravenous infusion of concentrated oxytocin ( 36 patients ) ; ( iv ) vaginal misoprostol ( 49 patients ) ; and ( v ) balloon insertion ( 73 patients ) . Oxytocin infusion was used in all but concentrated oxytocin group to augment labor , when necessary . Patients in whom effective uterine contractions and cervical dilatation was not obtained within 48 h with the primary termination method were registered as failures . RESULTS The efficacy of each method were evaluated in terms of abortion within time . Abortion within 48 h were achieved in 98.8 % ( 81/82 ) of the patients in ethacridine group ; 97.3 % ( 35/36 ) of the patients in concentrated oxytocin group ; 90.0 % ( 90/100 ) of the patients in PGE2 group ; 97.2 % ( 71/73 ) of the patients in balloon group ; 77.5 % ( 38/49 ) of the patients in misoprostol group ( P = 0.000 , P < 0.01 , Wilcoxon ( Gehan ) statistic ) . The overall median induction-abortion interval + /- S.D. ( in h ) in each group were as follows : ethacridine lactate : 15.7 + /- 9.6 , PGE2 gel : 20.0 + /- 14.5 , concentrated oxytocin : 12.2 + /- 14.4 , misoprostol : 24.0 + /- 22.2 , balloon : 16.0 + /- 15.4 ( one way ANOVA , P = 0.003 , P < 0.01 ) . CONCLUSION In comparison with the five methods , the use of extraamniotic ethacridine , intravenous concentrated oxytocin , and balloon was found to provide more effective treatment than intracervical PGE2 and misoprostol in terms of achievement of abortion within 24 and 48 |
1,688 | 28,744,879 | Chemotherapy-naive patients with HGG at first recurrence when treated with PCV or TMZ have similar survival and time-to-progression outcomes .
Adverse events are similar and QoL scores are statistically but not clinical ly significant between TMZ and PCV . | BACKGROUND Recurrent high- grade glioma ( HGG ) carries an extremely poor prognosis .
There is no current st and ard of care or guideline -based recommendations .
Nitrosourea-based multidrug chemotherapy or PCV - procarbazine , lomustine ( CCNU ) and vincristine - is one of the treatment options at recurrence .
There has been no meta- analysis which looks at the benefits and harms of PCV chemotherapy in adults with recurrent HGG .
OBJECTIVES To assess the effectiveness and safety of procarbazine , lomustine , and vincristine ( PCV ) chemotherapy with other interventions in adults with recurrent high- grade glioma .
To investigate whether predefined subgroups of people benefit more or less from chemotherapy . | Purpose : Patients with progressive or recurrent supratentorial high- grade gliomas were entered into a multicentre phase II trial to evaluate the efficacy and toxicity of temozolomide . Methods : The treatment schedule was 150–200 mg/m2 per day orally for 5 days repeated every 28 days . Response evaluation was by a combination of neurological status evaluation ( MRC scale ) and imaging . Results : Of 103 eligible patients enrolled , 11 ( 11 % ) achieved an objective response and a further 48 ( 47 % ) had stable disease . The median response duration was 4.6 months . Response rates were similar for anaplastic astrocytomas ( grade III ) and glioblastoma multiforme ( grade IV ) tumours . Predictable myelosuppression was the major toxicity . Conclusions : The observation of objective responses and tolerable side effects in this heterogeneous population of patients supports the further investigation of this agent in high- grade gliomas PURPOSE The st and ard of care for anaplastic gliomas is surgery followed by radiotherapy . The NOA-04 phase III trial compared efficacy and safety of radiotherapy followed by chemotherapy at progression with the reverse sequence in patients with newly diagnosed anaplastic gliomas . PATIENTS AND METHODS Patients ( N = 318 ) were r and omly assigned 2:1:1 ( A : B1:B2 ) to receive conventional radiotherapy ( arm A ) ; procarbazine , lomustine ( CCNU ) , and vincristine ( PCV ; arm B1 ) ; or temozolomide ( arm B2 ) at diagnosis . At occurrence of unacceptable toxicity or disease progression , patients in arm A were treated with PCV or temozolomide ( 1:1 r and om assignment ) , whereas patients in arms B1 or B2 received radiotherapy . The primary end point was time to treatment failure ( TTF ) , defined as progression after radiotherapy and one chemotherapy in either sequence . RESULTS Patient characteristics in the intention-to-treat population ( n = 274 ) were balanced between arms . All histologic diagnoses were central ly confirmed . Median TTF ( hazard ratio [ HR ] = 1.2 ; 95 % CI , 0.8 to 1.8 ) , progression-free survival ( PFS ; HR = 1.0 ; 95 % CI , 0.7 to 1.3 , and overall survival ( HR = 1.2 ; 95 % CI , 0.8 to 1.9 ) were similar for arms A and B1/B2 . Extent of resection was an important prognosticator . Anaplastic oligodendrogliomas and oligoastrocytomas share the same , better prognosis than anaplastic astrocytomas . Hypermethylation of the O(6)-methylguanine DNA-methyltransferase ( MGMT ) promoter ( HR = 0.59 ; 95 % CI , 0.36 to 1.0 ) , mutations of the isocitrate dehydrogenase ( IDH1 ) gene ( HR = 0.48 ; 95 % CI , 0.29 to 0.77 ) , and oligodendroglial histology ( HR = 0.33 ; 95 % CI , 0.2 to 0.55 ) reduced the risk of progression . Hypermethylation of the MGMT promoter was associated with prolonged PFS in the chemotherapy and radiotherapy arm . CONCLUSION Initial radiotherapy or chemotherapy achieved comparable results in patients with anaplastic gliomas . IDH1 mutations are a novel positive prognostic factor in anaplastic gliomas , with a favorable impact stronger than that of 1p/19q codeletion or MGMT promoter methylation A r and omized , multicentre , open-label , phase II study compared temozolomide ( TMZ ) , an oral second-generation alkylating agent , and procarbazine ( PCB ) in 225 patients with glioblastoma multiforme at first relapse . Primary objectives were to determine progression-free survival ( PFS ) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment . Secondary objectives were to assess overall survival and health-related quality of life ( HRQL ) . TMZ was given orally at 200 mg/m2/day or 150 mg/m2/day ( prior chemotherapy ) for 5 days , repeated every 28 days . PCB was given orally at 150 mg/m2/day or 125 mg/m2/day ( prior chemotherapy ) for 28 days , repeated every 56 days . HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 [ + 3 ] ) and the Brain Cancer Module 20 ( BCM20 ) . The 6-month PFS rate for patients who received TMZ was 21 % , which met the protocol objective . The 6-month PFS rate for those who received PCB was 8 % ( P = 0.008 , for the comparison ) . Overall PFS significantly improved with TMZ , with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group ( P = 0.0063 ) . The 6-month overall survival rate for TMZ patients was 60 % vs. 44 % for PCB patients ( P = 0.019 ) . Freedom from disease progression was associated with maintenance of HRQL , regardless of treatment received . TMZ had an acceptable safety profile ; most adverse events were mild or moderate in severity . © 2000 Cancer Research BACKGROUND Oligodendroglial tumors are chemosensitive , with two-thirds of patients responding to PCV combination chemotherapy with procarbazine , lomustine ( CCNU ) and vincristine . Temozolomide ( TMZ ) , a new alkylating and methylating agent has shown high response rates in recurrent anaplastic astrocytoma . We investigated this drug in recurrent oligodendroglial tumors ( OD ) and mixed oligoastrocytomas ( OA ) after prior PCV chemotherapy and radiation therapy . PATIENTS AND METHODS In a prospect i ve non-r and omized multicenter phase II trial patients were treated with TMZ 150 mg/m(2 ) on days 1 - 5 in cycles of 28 days for 12 cycles . Eligible patients had a recurrence after prior PCV chemotherapy , with measurable and enhancing disease as shown by magnetic resonance imaging . Pathology and all responses were central ly review ed . RESULTS Thirty-two eligible patients were included . In four patients the pathology review did not confirm the presence of an OD or OA . Twelve of 24 patients [ 50 % , 95 % confidence interval ( CI ) 29 % to 71 % ] evaluable for response to first-line PCV chemotherapy had responded to PCV . Temozolomide was in general well tolerated ; the most frequent side-effects were hematological . One patient discontinued treatment due to toxicity . In seven of 28 patients ( 25 % , 95 % CI 11 % to 45 % ) with histologically confirmed OD an objective response to TMZ was observed . Median time to progression for responding patients was 8.0 months . After 6 and 12 months from the start of treatment , 29 % and 11 % of patients , respectively , were still free from progression . CONCLUSIONS TMZ may be regarded as the preferred second-line treatment in OD after failure of PCV chemotherapy . Further studies on TMZ in OD are indicated The authors investigated the results of PCV chemotherapy within a cohort of 24 patients treated within the EORTC study 26971 on temozolomide chemotherapy in recurrent oligodendroglioma . The genotype of the tumors was assessed with fluorescent in situ hybridization with locus specific probes for the region 1p36 . Four of the 24 patients responded ( 17 % ) . Fifty percent of patients were still free from progression at 6 months and 21 % were free from progression at 12 months . Although a clear relation existed between loss of 1p and response to temozolomide chemotherapy , this relation was absent in salvage PCV chemotherapy PURPOSE Temozolomide ( TMZ ) is an alkylating agent licensed for treatment of high- grade glioma ( HGG ) . No prospect i ve comparison with nitrosourea-based chemotherapy exists . We report , to our knowledge , the first r and omized trial of procarbazine , lomustine , and vincristine ( PCV ) versus TMZ in chemotherapy-naive patients with recurrent HGG . PATIENTS AND METHODS Four hundred forty-seven patients were r and omly assigned to PCV ( 224 patients ) or TMZ ( sub-r and om assignment : TMZ-5 [ 200 mg/m(2 ) for 5 days , 112 patients ] or TMZ-21 [ 100 mg/m(2 ) for 21 days , 111 patients ] ) for up to 9 months or until progression . The primary outcomes were survival ( PCV v TMZ ) and 12-week progression-free survival ( PFS ; TMZ-5 v TMZ-21 ) . This study is registered as IS RCT N83176944 . RESULTS Percentages of patients completing 9 months of treatment in the PCV , TMZ-5 , and TMZ-21 arms were 17 % , 26 % , and 13 % , respectively . Major toxicity was similar across all three groups . With a median follow-up time of 12 months and 382 deaths , there was no clear survival benefit when comparing PCV with TMZ ( hazard ratio [ HR ] , 0.91 ; 95 % CI , 0.74 to 1.11 ; P = .350 ) . For TMZ-5 versus TMZ-21 , 12-week PFS rates were similar ( 63.6 % and 65.7 % , respectively ; P = .745 ) , but TMZ-5 improved overall PFS ( HR , 1.38 ; 95 % CI , 1.05 to 1.82 ; P = .023 ) , survival ( HR , 1.32 ; 95 % CI , 0.99 to 1.75 ; P = .056 ) , and global quality of life ( 49 % v 19 % improved > 10 points at 6 months , respectively ; P = .005 ) . CONCLUSION Although TMZ ( both arms combined ) did not show a clear benefit compared with PCV , comparison of the TMZ schedules demonstrated that the 21-day schedule was inferior to the 5-day schedule in this setting . This challenges the current underst and ing of increasing TMZ dose-intensity by prolonged scheduling PURPOSE Anaplastic oligodendroglioma are chemotherapy-sensitive tumors . We now present the long-term follow-up findings of a r and omized phase III study on the addition of six cycles of procarbazine , lomustine , and vincristine ( PCV ) chemotherapy to radiotherapy ( RT ) . PATIENTS AND METHODS Adult patients with newly diagnosed anaplastic oligodendroglial tumors were r and omly assigned to either 59.4 Gy of RT or the same RT followed by six cycles of adjuvant PCV . An exploratory analysis of the correlation between 1p/19q status and survival was part of the study . Retrospectively , the methylation status of the methyl-guanine methyl transferase gene promoter and the mutational status of the isocitrate dehydrogenase ( IDH ) gene were determined . The primary end points were overall survival ( OS ) and progression-free survival based on intent-to-treat analysis . RESULTS A total of 368 patients were enrolled . With a median follow-up of 140 months , OS in the RT/PCV arm was significantly longer ( 42.3 v 30.6 months in the RT arm , hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.60 to 0.95 ) . In the 80 patients with a 1p/19q codeletion , OS was increased , with a trend toward more benefit from adjuvant PCV ( OS not reached in the RT/PCV group v 112 months in the RT group ; HR , 0.56 ; 95 % CI , 0.31 to 1.03 ) . IDH mutational status was also of prognostic significance . CONCLUSION The addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors . 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non-1p/19q-deleted tumors The goal of this study was to determine the antitumor activity and toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea ( BCNU ) plus recombinant interferon-alpha ( IFN-alpha ) in patients with recurrent glioma . As single agents , both BCNU and IFN-alpha can cause tumor regression in patients with recurrent glioma . In vitro studies suggest synergy between the two agents . Thirty-five patients in whom computerized tomography ( CT ) or magnetic resonance ( MR ) evidence was obtained of progressive astrocytoma , oligoastrocytoma , or oligodendroglioma received recombinant IFN-alpha 2a ( 12 x 10(6 ) U/m2 intramuscularly ) on Days 1 through 3 and BCNU ( 150 mg/m2 intravenously ) on Day 3 of each 6-week cycle . All patients had tumor progression despite radiation therapy and had received no prior chemotherapy . Response was assessed by CT or MR evidence and by neurological examination while the patients were on a regimen of stable or decreasing doses of corticosteroids . All patients could be evaluated for response and toxicity . Twenty-nine percent of the patients demonstrated objective tumor regression ; 37 % remained stable for more than 6 months and 25 % were stable for less than 6 months . The median duration of response to IFN-alpha and BCNU was 9.9 months and the median survival for all patients was 13.3 months . Toxicity consisted primarily of moderate myelosuppression , venous irritation , vomiting , flulike symptoms , and transient reversible exacerbation of underlying neurological symptoms . The use of BCNU plus IFN-alpha is a safe , active regimen in the treatment of patients with recurrent glioma who have failed to respond to prior radiation therapy . The contribution of IFN to the antitumor activity observed in this study compared with that previously described with BCNU alone can not be assessed from this trial Ninety-nine patients bearing recurrent malignant glioma sequentially selected according to strict eligibility criteria ( 72 GBL and 27 AA ) entered the study . All patients were previously managed with radiotherapy 60 Gy total dose and chemotherapy with nitrosoureas and platinum compounds . At recurrence they were subdivided in homogeneous groups , all treated with the same systemic chemotherapy protocol : 27 GBL ( group A ) only systemically treated , 20 GBL ( group B ) treated also locally by delivering 4 mg of mitoxantrone every 20 days through the Ommaya reservoire , and 25 GBL ( group C ) treated with a second surgery and locally as group B. Of the AA group , 13/27 were treated locally trough the Ommaya reservoir after repeat surgery . A trend to different demographic features among subgroups ( with locoregionally treated patients and patients undergoing repeat surgery being younger than the others ) was seen in this non-r and omized study , but this was not statistically significant . Median overall survival was 27 , 26 and 15.5 months respectively for groups c , b and a ( log-rank = 0.1 ) . After tumor recurrence median survival was 16.8 , 12 and 6.6 months respectively for groups c , b and a ( log-rank = 0.001)For the 29 AA , overall survival was 48.5 and 100 months ( log-rank = 0.03 ) if treated locally with second tumor debulking . Our results stress the opinion that a second operation could be indicated only if it is a part of a therapeutic protocol to allow a locoregional treatment . Moreover we can finally assume that local delivery of chemotherapy after tumor recurrence , possibly extends patients survival but certainly improves the number of long-survivors PURPOSE Previous investigators have reported responses in 52 % of patients treated with mechlorethamine ( nitrogen mustard ) , vincristine , and procarbazine ( MOP ) for recurrent glioma . To confirm these promising results , we conducted a phase II prospect i ve study . PATIENTS AND METHODS Sixty-three patients with histologic confirmation of recurrent glioma were treated with the MOP regimen . Patients with or without prior chemotherapy received nitrogen mustard 3 mg/m2 or 6 mg/m2 , respectively , intravenously on days 1 and 8 plus vincristine 2 mg/m2 intravenously on days 1 and 8 , and procarbazine 100 mg/m2 orally on days 1 to 14 . Cycles were repeated every 28 days . RESULTS Of 61 patients assessable for response , eight responded ( 13 % ) , with one complete response ( CR ) . Responses were as follows : low- grade gliomas , 19 % ; anaplastic astrocytomas , 11 % ; anaplastic oligodendrogliomas or oligoastrocytomas , 25 % ; and glioblastomas , 4.3 % . The most common toxicity was myelosuppression with leukocyte nadirs less than 1,000/microL in 23 % and platelet nadirs less than 25,000/microL in 13 % of patients . Two patients died of infection in the setting of neutropenia . Nonhematologic toxicity included neurosensory changes in 21 % of patients ( severe in 3 % ) and severe dermatologic reactions in 8 % . In multivariate analysis , Eastern Cooperative Oncology group ( ECOG ) performance status ( PS ) was the best predictor for response to chemotherapy ( P=.01 ) and time to progression ( P=.008 ) , while PS and grade were the most important predictors of survival ( P=.002 and .05 , respectively ) . CONCLUSION This study did not confirm the high response rate previously reported in recurrent gliomas . Patients with recurrent anaplastic oligodendrogliomas or oligoastrocytomas and recurrent low- grade gliomas had the highest response rates ( 25 % and 19 % , respectively ) . In multivariate analysis , ECOG PS was the best predictor of response , while PS and tumor grade were the most important predictors of survival Background : Nitrosoureas constitute the main re source of chemotherapy for glioblastoma . However , because of chemoresistance , which is intrinsic or rapidly acquired after the first administration of chemotherapy , there have been few improvements in survival . Because O6-alkylguanine-DNA alkyltransferase ( AGT ) is the main target for increasing cell sensitivity to the nitrosoureas , we postulated that preexposure to other alkylating agents might increase the therapeutic index of the nitrosoureas by saturating all the copies of AGT present in the tumor cells . Objective : To investigate the response rate , toxic effects , time from start of chemotherapy to progression of disease or exit from the study for any reason ( TTP ) , and progression-free survival at 6 months ( PFS-6 ) associated with a multidrug combination that could reverse resistance to carmustine ( BCNU ) through AGT depletion . Methods : We conducted a phase 2 study of patients with glioblastoma at first relapse or progression after surgery and st and ard radiotherapy . Patients were treated with 100 mg/m2 of procarbazine on days 1 to 5 , 80 mg/m2 of BCNU on days 3 to 5 , and 1.4 mg/m2 of vincristine on day 3 every 8 weeks . Results : Fifty-eight patients were enrolled in the study , and all were assessable for response and toxic effects . Six patients ( 10.3 % ) had a complete response , 11 ( 19 % ) had a partial response , and 17 ( 29.3 % ) had stable disease . The median TTP was 4.8 months ; 42.3 % of patients had PFS-6 , and 15.4 % had PFS at 12 months . Response to chemotherapy was the only significant prognostic factor for TTP . Neutropenia was grade 3 in 8.6 % of patients and grade 4 in 5.2 % of patients , and thrombocytopenia was grade 3 in 17.2 % of patients and grade 4 in 12 % of patients ; hepatic and pulmonary toxic effects were grade 3 in 5.2 % and 8.6 % of patients , respectively . Conclusion : This regimen proved active in chemotherapy-naive patients with recurrent glioblastoma even though toxic effects were substantial Summary Thirty-five adult recurrent GBM patients , divided r and omly in two groups of 19 and 16 cases , had been treated with two regimens of chemotherapy : a ) ‘ eight-drugs-in-one-day ’ ; b ) procarbazine + CCNU + vincristine ( PCV ) respectively . Chemotherapy was planned at the tumor relapse and delivered as long as tolerated without irreversible sequelae or until the CT scan showed tumor progression . Multiple agents are used simultaneously in the therapeutic approach using ‘ eight-in-one ’ to kill as many heterogeneous cells of malignant glial tumor as possible and minimize the emergence of cellular resistance to chemotherapy . Rate response to chemotherapy and the median adjunctive survival time ( 6.5 and 6 months , respectively ) are not significantly different in the two arms of this study . Our experience with such an aggressive multi-drugs combination ‘ eight-in-one-day ’ was disappointing if compared with less toxic , better tolerated and easy delivered ( PCV ) regimen The authors administered procarbazine , 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea ( CCNU , lomustine ) , and vincristine ( PCV ) to 86 patients with recurrent glioblastoma . There were three partial responses , but no complete responses . Median progression-free survival was 17.1 weeks and progression-free survival at 6 months was 38.4 % . World Health Organization grade III/IV hematologic toxicity was common ( 25.6 % ) , but nonhematologic toxicity was mild PURPOSE Anaplastic oligodendrogliomas , pure ( AO ) and mixed ( anaplastic oligoastrocytoma [ AOA ] ) , are chemosensitive , especially if codeleted for 1p/19q , but whether patients live longer after chemoradiotherapy is unknown . PATIENTS AND METHODS Eligible patients with AO/AOA were r and omly assigned to procarbazine , lomustine , and vincristine ( PCV ) plus radiotherapy ( RT ) versus RT alone . The primary end point was overall survival ( OS ) . RESULTS Two hundred ninety-one eligible patients were r and omly assigned : 148 to PCV plus RT and 143 to RT . For the entire cohort , there was no difference in median survival by treatment ( 4.6 years for PCV plus RT v 4.7 years for RT ; hazard ratio [ HR ] = 0.79 ; 95 % CI , 0.60 to 1.04 ; P = .1 ) . Patients with codeleted tumors lived longer than those with noncodeleted tumors ( PCV plus RT : 14.7 v 2.6 years , HR = 0.36 , 95 % CI , 0.23 to 0.57 , P < .001 ; RT : 7.3 v 2.7 years , HR = 0.40 , 95 % CI , 0.27 to 0.60 , P < .001 ) , and the median survival of those with codeleted tumors treated with PCV plus RT was twice that of patients receiving RT ( 14.7 v 7.3 years ; HR = 0.59 ; 95 % CI , 0.37 to 0.95 ; P = .03 ) . For those with noncodeleted tumors , there was no difference in median survival by treatment arm ( 2.6 v 2.7 years ; HR = 0.85 ; 95 % CI , 0.58 to 1.23 ; P = .39 ) . In Cox models that included codeletion status , the adjusted OS for all patients was prolonged by PCV plus RT ( HR = 0.67 ; 95 % CI , 0.50 to 0.91 ; P = .01 ) . CONCLUSION For the subset of patients with 1p/19q codeleted AO/AOA , PCV plus RT may be an especially effective treatment , although this observation was derived from an unplanned analysis |
1,689 | 22,047,889 | There was no evidence that the observational studies pre date d RCTs in the translational process in either example .
In the two examples , citation network characteristics do not predict concordance in the results of observational studies and RCTs | OBJECTIVE There are several examples in nutrition of discordance between the results of observational studies and r and omized controlled trials ( RCTs ) .
We hypothesized that this discordance is attributable to differences in the translational paths of nutrient-disease associations .
Translational paths can be assessed using citation analysis . | BACKGROUND Omega-3 fatty acids , such as those present in fish oil , have been reported to prolong life in myocardial infa rct ion survivors . These fatty acids can decrease serum triglyceride concentrations , but so far the doses used in trials examining their effects on coronary end points have had only minimal triglyceride lowering effects . OBJECTIVE To examine the triglyceride lowering effectiveness , safety , and tolerability of Omacor , a concentrate of omega-3 , long chain , polyunsaturated fatty acids from fish oil ( 84 % of the total as opposed to an average of 35 % in fish oil ) over one year in patients with established coronary heart disease ( CHD ) and persisting hypertriglyceridaemia , despite receiving simvastatin in doses similar to those employed in the Sc and inavian simvastatin survival study . SUBJECTS AND METHODS 59 patients with CHD , receiving simvastatin 10–40 mg daily with serum triglycerides > 2.3 mmol/l , were r and omised to receive Omacor 2 g twice a day or placebo for 24 weeks in a double blind trial . Forty six patients accepted the offer of active treatment for a further 24 weeks in an open phase of the trial . RESULTS There was a sustained significant decrease in serum triglycerides by 20–30 % ( p < 0.005 ) and in very low density lipoprotein ( VLDL ) cholesterol by 30–40 % ( p < 0.005 ) in patients receiving active Omacor at three , six , and 12 months compared either to baseline or placebo . Omacor did not have any deleterious effect on low density or high density lipoprotein cholesterol or on biochemical and haematological safety tests . There was no adverse effect on glycaemic control in patients with diabetes , who showed a decrease in serum triglyceride , which was at least as great as in non-diabetic patients . One patient receiving placebo died of acute myocardial infa rct ion . Three patients withdrew from the trial ( two on placebo and one on active treatment ) . Omacor was generally well tolerated . CONCLUSION Omacor was found to be a safe and effective means of lowering serum triglycerides over one year in patients with CHD and combined hyperlipidaemia , whose triglycerides remained elevated despite simvastatin treatment BACKGROUND We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas , which are precursors of most large-bowel cancers . METHODS We r and omly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before r and omization to one of two groups : an intervention group given intensive counseling and assigned to follow a diet that was low in fat ( 20 percent of total calories ) and high in fiber ( 18 g of dietary fiber per 1000 kcal ) and fruits and vegetables ( 3.5 servings per 1000 kcal ) , and a control group given a st and ard brochure on healthy eating and assigned to follow their usual diet . Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps ; they remained in the study for approximately four years , undergoing colonoscopy one and four years after r and omization . RESULTS A total of 1905 of the r and omized subjects ( 91.6 percent ) completed the study . Of the 958 subjects in the intervention group and the 947 in the control group who completed the study , 39.7 percent and 39.5 percent , respectively , had at least one recurrent adenoma ; the unadjusted risk ratio was 1.00 ( 95 percent confidence interval , 0.90 to 1.12 ) . Among subjects with recurrent adenomas , the mean ( + /-SE ) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group . The rate of recurrence of large adenomas ( with a maximal diameter of at least 1 cm ) and advanced adenomas ( defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high- grade dysplasia , including carcinoma ) did not differ significantly between the two groups . CONCLUSIONS Adopting a diet that is low in fat and high in fiber , fruits , and vegetables does not influence the risk of recurrence of colorectal adenomas BACKGROUND The Lyon Diet Heart Study is a r and omized secondary prevention trial aim ed at testing whether a Mediterranean-type diet may reduce the rate of recurrence after a first myocardial infa rct ion . An intermediate analysis showed a striking protective effect after 27 months of follow-up . This report presents results of an extended follow-up ( with a mean of 46 months per patient ) and deals with the relationships of dietary patterns and traditional risk factors with recurrence . METHODS AND RESULTS Three composite outcomes ( COs ) combining either cardiac death and nonfatal myocardial infa rct ion ( CO 1 ) , or the preceding plus major secondary end points ( unstable angina , stroke , heart failure , pulmonary or peripheral embolism ) ( CO 2 ) , or the preceding plus minor events requiring hospital admission ( CO 3 ) were studied . In the Mediterranean diet group , CO 1 was reduced ( 14 events versus 44 in the prudent Western-type diet group , P=0.0001 ) , as were CO 2 ( 27 events versus 90 , P=0.0001 ) and CO 3 ( 95 events versus 180 , P=0 . 0002 ) . Adjusted risk ratios ranged from 0.28 to 0.53 . Among the traditional risk factors , total cholesterol ( 1 mmol/L being associated with an increased risk of 18 % to 28 % ) , systolic blood pressure ( 1 mm Hg being associated with an increased risk of 1 % to 2 % ) , leukocyte count ( adjusted risk ratios ranging from 1.64 to 2.86 with count > 9x10(9)/L ) , female sex ( adjusted risk ratios , 0.27 to 0 . 46 ) , and aspirin use ( adjusted risk ratios , 0.59 to 0.82 ) were each significantly and independently associated with recurrence . CONCLUSIONS The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infa rct ion , confirming previous intermediate analyses . Major traditional risk factors , such as high blood cholesterol and blood pressure , were shown to be independent and joint predictors of recurrence , indicating that the Mediterranean dietary pattern did not alter , at least qualitatively , the usual relationships between major risk factors and recurrence . Thus , a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet . It should be associated with other ( pharmacological ? ) means aim ed at reducing modifiable risk factors . Further trials combining the 2 approaches are warranted BACKGROUND Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease . We aim ed to test the hypothesis that long-term use of eicosapentaenoic acid ( EPA ) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish . METHODS 18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999 . Patients were r and omly assigned to receive either 1800 mg of EPA daily with statin ( EPA group ; n=9326 ) or statin only ( controls ; n=9319 ) with a 5-year follow-up . The primary endpoint was any major coronary event , including sudden cardiac death , fatal and non-fatal myocardial infa rct ion , and other non-fatal events including unstable angina pectoris , angioplasty , stenting , or coronary artery bypass grafting . Analysis was by intention-to-treat . The study was registered at Clinical Trials.gov , number NCT00231738 . FINDINGS At mean follow-up of 4.6 years , we detected the primary endpoint in 262 ( 2.8 % ) patients in the EPA group and 324 ( 3.5 % ) in controls-a 19 % relative reduction in major coronary events ( p=0.011 ) . Post-treatment LDL cholesterol concentrations decreased 25 % , from 4.7 mmol/L in both groups . Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events . Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group . Sudden cardiac death and coronary death did not differ between groups . In patients with a history of coronary artery disease who were given EPA treatment , major coronary events were reduced by 19 % ( secondary prevention subgroup : 158 [ 8.7 % ] in the EPA group vs 197 [ 10.7 % ] in the control group ; p=0.048 ) . In patients with no history of coronary artery disease , EPA treatment reduced major coronary events by 18 % , but this finding was not significant ( 104 [ 1.4 % ] in the EPA group vs 127 [ 1.7 % ] in the control group ; p=0.132 ) . INTERPRETATION EPA is a promising treatment for prevention of major coronary events , and especially non-fatal coronary events , in Japanese hypercholesterolaemic patients BACKGROUND Recent studies indicate that depression plays an important role in the occurrence of cardiovascular diseases ( CVDs ) . The underlying mechanisms are not well understood . OBJECTIVE We investigated whether dietary intake of the n-3 fatty acids ( FAs ) eicosapentaenic acid and docosahexaenoic acid could explain the relation between depressive symptoms and cardiovascular mortality . DESIGN The Zutphen Elderly Study is a prospect i ve cohort study conducted in the Netherl and s. Depressive symptoms were measured in 1990 with the Zung Self-rating Depression Scale in 332 men aged 70 - 90 y and free from CVD and diabetes . Dietary factors were assessed with a cross-check dietary history method in 1990 . Mortality data were collected between 1990 and 2000 . Logistic and Cox regression analyses were performed , with adjustment for demographics and CVD risk factors . RESULTS Compared with a low intake ( x : 21 mg/d ) , a high intake ( x : 407 mg/d ) of n-3 FAs was associated with fewer depressive symptoms [ odds ratio : 0.46 ; 95 % CI : 0.22 , 0.95 ; P for trend = 0.04 ] at baseline and no significant reduced risk of 10-y CVD mortality [ hazard ratio ( HR ) : 0.88 ; 95 % CI : 0.51 , 1.50 ] . The adjusted HR for an increase in depressive symptoms with 1 SD for CVD mortality was 1.28 ( 95 % CI : 1.03 , 1.57 ) and did not change after additional adjustment for the intake of n-3 FAs . CONCLUSION An average intake of approximately 400 mg n-3 FA/d may reduce the risk of depression . Our results , however , do not support the hypothesis that the intake of n-3 FAs explains the relation between depression and CVD BACKGROUND Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and may improve prognosis . OBJECTIVE The objective was to evaluate the effect of a high-dose ethylester concentrate of n-3 fatty acids administered early after an acute myocardial infa rct ion ( MI ) on subsequent cardiac events and serum lipids . DESIGN Three hundred patients with acute MI were r and omly assigned to a daily dose of either 4 g highly concentrated n-3 fatty acids or corn oil , administered in a double-blind manner over 12 - 24 mo . Median follow-up time was 1.5 y. Clinical follow-up , including the drawing of blood sample s , was performed after 6 wk of treatment and later at 0.5-year intervals . RESULTS Forty-two ( 28 % ) patients in the n-3 group and 36 ( 24 % ) in the corn oil group experienced at least one cardiac event ( cardiac death , resuscitation , recurrent MI , or unstable angina ) . No significant difference in prognosis was observed between groups for single or combined cardiac events . Total cholesterol concentrations decreased in both groups , with no significant intergroup differences . On average , the monthly increase in HDL cholesterol was 1.11 % in the n-3 group and 0.55 % in the corn oil group ( P = 0.0016 ) . Triacylglycerol concentrations decreased by 1.30%/mo in the n-3 group , whereas they increased by 0.35%/mo in the corn oil group ( P < 0.0001 ) . CONCLUSION No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids BACKGROUND AND AIMS epidemiological studies suggest polyunsaturated fatty acids protect against the development of atherosclerosis . The aim of this study was to perform a r and omized controlled trial of gamma-linolenic and eicosapentaenoic acids in patients with lower limb atherosclerosis . Main outcome measures were : cholesterol and lipoprotein concentrations ; haemostatic and rheological variables ; the ankle brachial pressure index ; walking distance ; and cardiovascular events and death . METHODS 120 men and women with stable intermittent claudication were r and omized to 2 years treatment with either a combination of gamma-linolenic and eicosapentaenoic acids , or placebo . RESULTS 39 ( 65.0 cent ) of those taking fatty acids and 36 ( 60.0 cent ) of those taking placebo completed the trial . Lipid concentrations did not differ significantly during the trial . In those taking fatty acids , haematocrit was significantly higher than in the placebo group after 6 months ( 46.1 cent compared with 44.6 cent , P < /= 0.01 ) , and systolic blood pressure was significantly lower after 2 years ( 150|mmHg compared with 161.8|mmHg , < /= 0.05 ) . There was no difference in walking distance , but there was a small reduction in non-fatal coronary events in the fatty acid group ( 10 cent compared with 15 cent , P > 0.05 ) . CONCLUSIONS a combination of polyunsaturated fatty acids produced a statistically significant reduction in systolic blood pressure , but no other significant benefits on risk factors . The trend towards fewer coronary events in those taking fatty acids warrants further investigation BACKGROUND Atrial fibrillation ( AF ) is the most common arrhythmia in clinical practice and is particularly common in the elderly . Although effects of fish intake , including potential antiarrhythmic effects , may favorably influence risk of AF , relationships between fish intake and AF incidence have not been evaluated . METHODS AND RESULTS In a prospect i ve , population -based cohort of 4815 adults > or = age 65 years , usual dietary intake was assessed at baseline in 1989 and 1990 . Consumption of tuna and other broiled or baked fish correlated with plasma phospholipid long-chain n-3 fatty acids , whereas consumption of fried fish or fish s and wiches ( fish burgers ) did not . AF incidence was prospect ively ascertained on the basis of hospital discharge records and annual electrocardiograms . During 12 years ' follow-up , 980 cases of incident AF were diagnosed . In multivariate analyses , consumption of tuna or other broiled or baked fish was inversely associated with incidence of AF , with 28 % lower risk with intake 1 to 4 times per week ( HR=0.72 , 95 % CI=0.58 to 0.91 , P=0.005 ) , and 31 % lower risk with intake > or = 5 times per week ( HR=0.69 , 95 % CI=0.52 to 0.91 , P=0.008 ) , compared with < 1 time per month ( P trend=0.004 ) . Results were not material ly different after adjustment for preceding myocardial infa rct ion or congestive heart failure . In similar analyses , fried fish/fish s and wich consumption was not associated with lower risk of AF . CONCLUSIONS Among elderly adults , consumption of tuna or other broiled or baked fish , but not fried fish or fish s and wiches , is associated with lower incidence of AF . Fish intake may influence risk of this common cardiac arrhythmia BACKGROUND Sudden death ( SD ) has a major impact on mortality ( M ) in patients with left ventricular systolic dysfunction ( SyD ) . In GISSI-Prevenzione , treatment with n-3 polyunsaturated fatty acids ( PUFA ) reduced M and SD in post-MI patients , but their effect in patients with SyD is unknown . METHODS 11,323 patients with prior MI and NYHA class < or = II were recruited . After excluding patients with no ejection fraction ( EF ) measurement ( 1684 ) , and those with missing data ( n=9 ) , 9630 patients were available for analysis . Multivariate Cox regression adjusted models were fitted . RESULTS Compared to patients with EF > 50 % , SyD patients had higher M ( 12.3 % vs. 6.0 % ) and SD ( 3.4 % vs. 1.4 % ) rates . PUFA reduced M similarly in patients with ( RR 0.76 ( 0.60 - 0.96 ) P=0.02 ) and without SyD ( RR 0.81 ( 0.59 - 1.10 ) P=0.17 ) ( heterogeneity tests P=0.55 ) . In contrast , the effect on SD was markedly asymmetrical : PUFA produced a marked reduction ( RR 0.42 ( 0.26 - 0.67 ) P=0.0003 ) of risk in SyD patients whereas the effect was less evident ( RR 0.89 ( 0.41 - 1.69 ) P=0.71 ) in patients with EF > 50 % ( heterogeneity tests P=0.07 ) . There was a significant increase in SD with worsening EF ( P test for trend=0.02 ) , the benefit on SD in patients with EF < or = 40 % being 4-fold higher than in those with EF > 50 % . CONCLUSIONS Increasing SyD is associated with elevated risk of SD and with increasing benefit from PUFA . The effect of PUFA on SD reduction was greater in patients with SyD. Prospect i ve trials testing the effect of PUFA in population s with SyD are required Objective : Although animal studies suggest an inverse association between consumption of plant foods and risk of colorectal cancer , many observational data have failed to support such an association . We prospect ively examined the association between dietary intakes of fruit , vegetables , and fiber and colorectal cancer risk in a large female cohort from the Women ’s Health Study . Methods : Among 39,876 healthy women aged ≥45 years at baseline , 36,976 with baseline self-reported information on dietary intakes and other risk factors for colorectal cancer were included in the analyses . During an average follow-up of 10 years , 223 women were diagnosed with colorectal cancer . Intakes of fruit , vegetables , and fiber were assessed by a baseline food-frequency question naire . The analyses were carried out using the Cox proportional hazards regression and all tests were two-sided . Results : Intakes of fruit , vegetables , and the specific subgroups were not found to be associated with colorectal cancer risk . Multivariate relative risks ( RRs ) comparing the highest with lowest quintile were 0.79 ( 95 % CI = 0.49–1.27,pfor trend = 0.30 ) for fruit intake , and 0.88 ( 95 % CI=0.56–1.38,pfor trend=0.30 ) for vegetables intake . Similarly , intake of total fiber was not associated with colorectal cancer risk ; the RR for the highest relative to lowest quintile was 0.75 ( 95 % CI=0.48–1.17,pfor trend=0.12 ) . However , higher intake of legume fiber was associated with a lower risk of colorectal cancer ; the RR for the highestversuslowest quintile was 0.60 ( 95 % CI=0.40–0.91,pfor trend=0.02 ) . Conclusions : Our data offer little support for associations between intakes of fruit , vegetables , and fiber , and colorectal cancer risk . However , our data suggest that legume fiber and /or other related sources may reduce risk of colorectal cancer OBJECTIVE —To examine ethnic differences in risk of type 2 diabetes , taking dietary and lifestyle risk factors into account . RESEARCH DESIGN AND METHODS —A prospect i ve ( 1980–2000 ) cohort ( from The Nurses ’ Health Study ) including 78,419 apparently healthy women ( 75,584 whites , 801 Asians , 613 Hispanics , and 1,421 blacks ) was studied . Detailed dietary and lifestyle information for each participant was repeatedly collected every 4 years . RESULTS —During 1,294,799 person-years of follow-up , we documented 3,844 incident cases of diabetes . Compared with whites , the age-adjusted relative risks ( RRs ) were 1.43 ( 95 % CI 1.08–1.90 ) for Asians , 1.76 ( 1.32–2.34 ) for Hispanics , and 2.18 ( 1.82–2.61 ) for blacks . After adjustment for BMI , the RRs changed to 2.26 ( 1.70–2.99 ) for Asians , 1.86 ( 1.40–2.47 ) for Hispanics , and 1.34 ( 1.12–1.61 ) for blacks . For each 5-unit increment in BMI , the multivariate RR of diabetes was 2.36 ( 1.83–3.04 ) for Asians , 2.21 ( 1.75–2.79 ) for Hispanics , 1.96 ( 1.93–2.00 ) for whites , and 1.55 ( 1.36–1.77 ) for blacks ( P for interaction < 0.001 ) . For each 5-kg weight gain between age 18 and the year 1980 , the risk of diabetes was increased by 84 % ( 95 % CI 58–114 ) for Asians , 44 % ( 26–63 ) for Hispanics , 38 % ( 28–49 ) for blacks , and 37 % ( 35–38 % ) for whites . A healthy diet high in cereal fiber and polyunsaturated fat and low in trans fat and glycemic load was more strongly associated with a lower risk of diabetes among minorities ( RR 0.54 [ 95 % CI 0.39–0.73 ] ) than among whites ( 0.77 [ 0.72–0.84 ] ) . CONCLUSIONS —The risk of diabetes is significantly higher among Asians , Hispanics , and blacks than among whites before and after taking into account differences in BMI . Weight gain is particularly detrimental for Asians . Our data suggest that the inverse association of a healthy diet with diabetes is stronger for minorities than for whites Background —Epidemiological studies have demonstrated an inverse relationship between vitamin E intake and cardiovascular disease ( CVD ) risk . In contrast , r and omized controlled trials have reported conflicting results as to whether vitamin E supplementation reduces atherosclerosis progression and CVD events . Methods and Results —The study population consisted of men and women ≥40 years old with an LDL cholesterol level ≥3.37 mmol/L ( 130 mg/dL ) and no clinical signs or symptoms of CVD . Eligible participants were r and omized to DL-&agr;-tocopherol 400 IU per day or placebo and followed every 3 months for an average of 3 years . The primary trial end point was the rate of change in the common carotid artery far-wall intima-media thickness ( IMT ) assessed by computer image-processed B-mode ultrasonograms . A mixed effects model using all determinations of IMT was used to test the hypothesis of treatment differences in IMT change rates . Compared with placebo , & agr;-tocopherol supplementation significantly raised plasma vitamin E levels ( P < 0.0001 ) , reduced circulating oxidized LDL ( P = 0.03 ) , and reduced LDL oxidative susceptibility ( P < 0.01 ) . However , vitamin E supplementation did not reduce the progression of IMT over a 3-year period compared with subjects r and omized to placebo . Conclusions —The results are consistent with previous r and omized controlled trials and extend the null results of vitamin E supplementation to the progression of IMT in healthy men and women at low risk for CVD Objective — Clinical trials of vitamin E have failed to demonstrate a decrease in cardiovascular events . However , these studies did not address possible benefit to subgroups with increased oxidative stress . Haptoglobin ( Hp ) , a major antioxidant protein , is a determinant of cardiovascular events in patients with Type 2 diabetes mellitus ( DM ) . The Hp gene is polymorphic with 2 common alleles , 1 and 2 . The Hp 2 allelic protein product provides inferior antioxidant protection compared with the Hp 1 allelic product . We sought to test the hypothesis that vitamin E could reduce cardiovascular events in DM individuals with the Hp 2 - 2 genotype , a subgroup that comprises 2 % to 3 % of the general population . Methods and Results —1434 DM individuals ≥55 years of age with the Hp 2 - 2 genotype were r and omized to vitamin E ( 400 U/d ) or placebo . The primary composite outcome was myocardial infa rct ion , stroke , and cardiovascular death . At the first evaluation of events , 18 months after initiating the study , the primary outcome was significantly reduced in individuals receiving vitamin E ( 2.2 % ) compared with placebo ( 4.7 % ; P=0.01 ) and led to early termination of the study . Conclusions —Vitamin E supplementation appears to reduce cardiovascular events in individuals with DM and the Hp 2 - 2 genotype ( Clinical Trials.gov NCT00220831 ) OBJECTIVES This r and omized clinical trial tested whether fish oil supplements can improve human coronary atherosclerosis . BACKGROUND Epidemiologic studies of population s whose intake of oily fish is high , as well as laboratory studies of the effects of the polyunsaturated fatty acids in fish oil , support the hypothesis that fish oil is antiatherogenic . METHODS Patients with angiographically documented coronary heart disease and normal plasma lipid levels were r and omized to receive either fish oil capsules ( n = 31 ) , containing 6 g of n-3 fatty acids , or olive oil capsules ( n = 28 ) for an average duration of 28 months . Coronary atherosclerosis on angiography was quantified by computer-assisted image analysis . RESULTS Mean ( + /- SD ) baseline characteristics were age 62 + /- 7 years , plasma total cholesterol concentration 187 + /- 31 mg/dl ( 4.83 + /- 0.80 mmol/liter ) and triglyceride levels 132 + /- 70 mg/dl ( 1.51 + /- 0.80 mmol/liter ) . Fish oil lowered triglyceride levels by 30 % ( p = 0.007 ) but had no significant effects on other plasma lipoprotein levels . At the end of the trial , eicosapentaenoic acid in adipose tissue sample s was 0.91 % in the fish oil group compared with 0.20 % in the control group ( p < 0.0001 ) . At baseline , the minimal lumen diameter of coronary artery lesions ( n = 305 ) was 1.64 + /- 0.76 mm , and percent narrowing was 48 + /- 14 % . Mean minimal diameter of atherosclerotic coronary arteries decreased by 0.104 and 0.138 mm in the fish oil and control groups , respectively ( p = 0.6 between groups ) , and percent stenosis increased by 2.4 % and 2.6 % , respectively ( p = 0.8 ) . Confidence intervals exclude improvement by fish oil treatment of > 0.17 mm , or > 2.6 % . CONCLUSIONS Fish oil treatment for 2 years does not promote major favorable changes in the diameter of atherosclerotic coronary arteries Background — The long-chain n-3 fatty acids in fish have been demonstrated to have antiarrhythmic properties in experimental models and to prevent sudden cardiac death in a r and omized trial of post – myocardial infa rct ion patients . Therefore , we hypothesized that these n-3 fatty acids might prevent potentially fatal ventricular arrhythmias in high-risk patients . Methods and Results — Four hundred two patients with implanted cardioverter/defibrillators ( ICDs ) were r and omly assigned to double-blind treatment with either a fish oil or an olive oil daily supplement for 12 months . The primary end point , time to first ICD event for ventricular tachycardia or fibrillation ( VT or VF ) confirmed by stored electrograms or death from any cause , was analyzed by intention to treat . Secondary analyses were performed for “ probable ” ventricular arrhythmias , “ on-treatment ” analyses for all subjects who had taken any of their oil supplements , and “ on-treatment ” analyses only of those subjects who were on treatment for at least 11 months . Compliance with double-blind treatment was similar in the 2 groups ; however , the noncompliance rate was high ( 35 % of all enrollees ) . In the primary analysis , assignment to treatment with the fish oil supplement showed a trend toward a prolonged time to the first ICD event ( VT or VF ) or of death from any cause ( risk reduction of 28 % ; P=0.057 ) . When therapies for probable episodes of VT or VF were included , the risk reduction became significant at 31 % ; P=0.033 . For those who stayed on protocol for at least 11 months , the antiarrhythmic benefit of fish oil was improved for those with confirmed events ( risk reduction of 38 % ; P=0.034 ) . Conclusions — Although significance was not achieved for the primary end point , this study provides evidence that for individuals at high risk of fatal ventricular arrhythmias , regular daily ingestion of fish oil fatty acids may significantly reduce potentially fatal ventricular arrhythmias Between 1986 and 1989 , 18,244 men aged 45 - 64 years in Shanghai , China , participated in a prospect i ve study of diet and cancer . All participants completed an in-person , structured interview and provided blood and urine sample s. As of September 1 , 1998 , 113 deaths from acute myocardial infa rct ion were identified . After analyses were adjusted for age , total energy intake , and known cardiovascular disease risk factors , men who consumed > or=200 g of fish/shellfish per week had a relative risk of 0.41 ( 95 % confidence interval : 0.22 , 0.78 ) for fatal acute myocardial infa rct ion compared with men consuming < 50 g per week . Similarly , dietary intake of n-3 fatty acids derived from seafood also was significantly associated with reduced mortality from myocardial infa rct ion . Neither dietary seafood nor n-3 fatty acid intake was associated with a reduced risk of death from stroke or ischemic heart disease other than acute myocardial infa rct ion . However , approximately a 20 % reduction in total mortality associated with weekly fish/shellfish intake was observed in the study population ( relative risk = 0.79 , 95 % confidence interval : 0.69 , 0.91 ) . These prospect i ve data suggest that eating fish and shellfish weekly reduces the risk of fatal myocardial infa rct ion in middle-aged and older men in Shanghai , China BACKGROUND Observational studies suggested that a diet high in fruits and vegetables , both of which are rich with antioxidants , may prevent cancer development . However , findings from r and omized trials of the association between antioxidant use and cancer risk have been mostly negative . METHODS From 8171 women who were r and omly assigned in the Women 's Antioxidant Cardiovascular Study , a double-blind , placebo-controlled 2 x 2 x 2 factorial trial of vitamin C ( 500 mg of ascorbic acid daily ) , natural- source vitamin E ( 600 IU of alpha-tocopherol every other day ) , and beta carotene ( 50 mg every other day ) , 7627 women who were free of cancer before r and om assignment were selected for this study . Diagnoses and deaths from cancer at a specific site were confirmed by use of hospital reports and the National Death Index . Cox proportional hazards regression models were used to assess hazard ratios ( represented as relative risks [ RRs ] ) of common cancers associated with use of antioxidants , either individually or in combination . Subgroup analyses were conducted to determine if duration of use modified the association of supplement use with cancer risk . All statistical tests were two-sided . RESULTS During an average 9.4 years of treatment , 624 women developed incident invasive cancer and 176 women died from cancer . There were no statistically significant effects of use of any antioxidant on total cancer incidence . Compared with the placebo group , the RRs were 1.11 ( 95 % confidence interval [ CI ] = 0.95 to 1.30 ) in the vitamin C group , 0.93 ( 95 % CI = 0.79 to 1.09 ) in the vitamin E group , and 1.00 ( 95 % CI = 0.85 to 1.17 ) in the beta carotene group . Similarly , no effects of these antioxidants were observed on cancer mortality . Compared with the placebo group , the RRs were 1.28 ( 95 % CI = 0.95 to 1.73 ) in the vitamin C group , 0.87 ( 95 % CI = 0.65 to 1.17 ) in the vitamin E group , and 0.84 ( 95 % CI = 0.62 to 1.13 ) in the beta carotene group . Duration and combined use of the three antioxidants also had no effect on cancer incidence and cancer death . CONCLUSIONS Supplementation with vitamin C , vitamin E , or beta carotene offers no overall benefits in the primary prevention of total cancer incidence or cancer mortality BACKGROUND Few studies have examined associations of fish consumption with ischemic heart disease ( IHD ) risk among older adults or how different types of fish meals relate to IHD risk . METHODS AND RESULTS In a population -based prospect i ve cohort study , usual fish consumption was ascertained at baseline among 3910 adults aged > or = 65 years and free of known cardiovascular disease in 1989 and 1990 . Consumption of tuna and other broiled or baked fish correlated with plasma phospholipid long-chain n-3 fatty acids , whereas consumption of fried fish or fish s and wiches ( fish burgers ) did not . Over 9.3 years ' mean follow-up , there were 247 IHD deaths ( including 148 arrhythmic deaths ) and 363 incident nonfatal myocardial infa rct ions ( MIs ) . After adjustment for potential confounders , consumption of tuna or other broiled or baked fish was associated with lower risk of total IHD death ( P for trend=0.001 ) and arrhythmic IHD death ( P=0.001 ) but not nonfatal MI ( P=0.44 ) , with 49 % lower risk of total IHD death and 58 % lower risk of arrhythmic IHD death among persons consuming tuna/other fish 3 or more times per week compared with less than once per month . In similar analyses , fried fish/fish s and wich consumption was not associated with lower risk of total IHD death , arrhythmic IHD death , or nonfatal MI but rather with trends toward higher risk . CONCLUSIONS Among adults aged > or = 65 years , modest consumption of tuna or other broiled or baked fish , but not fried fish or fish s and wiches , is associated with lower risk of IHD death , especially arrhythmic IHD death . Cardiac benefits of fish consumption may vary depending on the type of fish meal consumed OBJECTIVE We investigated in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with type 2 diabetes . RESEARCH DESIGN AND METHODS The Primary Prevention Project ( PPP ) is a r and omized , open trial with a two-by-two factorial design aim ed to investigate low-dose aspirin ( 100 mg/day ) and vitamin E ( 300 mg/day ) in the prevention of cardiovascular events in patients with one or more cardiovascular risk factors . The primary end point was a composite end point of cardiovascular death , stroke , or myocardial infa rct ion . A total of 1,031 people with diabetes in the PPP , aged > /=50 years , without a previous cardiovascular event were enrolled by 316 general practitioners and 14 diabetes outpatient clinics . RESULTS The PPP trial was prematurely stopped ( after a median of 3.7 years ) by the independent data safety and monitoring board because of a consistent benefit of aspirin compared with the control group in a population of 4,495 patients with one or more major cardiovascular risk factors . In diabetic patients , aspirin treatment was associated with a nonsignificant reduction in the main end point ( relative risk [ RR ] = 0.90 , 95 % CI 0.50 - 1.62 ) and in total cardiovascular events ( 0.89 , 0.62 - 1.26 ) and with a nonsignificant increase in cardiovascular deaths ( 1.23 , 0.69 - 2.19 ) . In nondiabetic subjects , RRs for the main end point , total cardiovascular events , and cardiovascular deaths were 0.59 ( 0.37 - 0.94 ) , 0.69 ( 0.53 - 0.90 ) , and 0.32 ( 0.14 - 0.72 ) , respectively . No significant reduction in any of the end points considered could be found with vitamin E in either diabetic or nondiabetic subjects . CONCLUSIONS Our data suggest a lower effect of primary prevention of cardiovascular disease ( CVD ) with low-dose aspirin in diabetic patients as opposed to subjects with other cardiovascular risk factors . If confirmed , these findings might indicate that the antiplatelet effects of aspirin in diabetic patients are overwhelmed by aspirin-insensitive mechanisms of platelet activation and thrombus formation , thus making the balance between benefits and harms of aspirin treatment unfavorable . Further large-scale trials investigating the role of aspirin in the primary prevention of CVD in diabetic patients are urgently needed OBJECTIVE To explore the association of supplementary and dietary vitamin E and C intake with the progression of coronary artery disease . DESIGN A subgroup analysis of the on-trial antioxidant vitamin intake data base acquired in the Cholesterol Lowering Atherosclerosis Study , a r and omized , placebo-controlled , serial angiographic clinical trial evaluating the risk and benefit of colestipol-niacin on coronary artery disease progression . SETTING Community- and university-based cardiac catheterization laboratories . SUBJECTS A total of 156 men aged 40 to 59 years with previous coronary artery bypass graft surgery . INTERVENTION Supplementary and dietary vitamin E and C intake ( nonr and omized ) in association with cholesterol-lowering diet and either colestipol-niacin or placebo ( r and omized ) . OUTCOME Change per subject in the percentage of vessel diameter obstructed because of stenosis ( % S ) determined by quantitative coronary angiography after 2 years of r and omized therapy on all lesions , mild/moderate lesions ( < 50%S ) , and severe lesions ( > or = 50%S ) . RESULTS Overall , subjects with supplementary vitamin E intake of 100 IU per day or greater demonstrated less coronary artery lesion progression than did subjects with supplementary vitamin E intake less than 100 IU per day for all lesions ( P = .04 ) and for mild/moderate lesions ( P = .01 ) . Within the drug group , benefit of supplementary vitamin E intake was found for all lesions ( P = .02 ) and mild/moderate lesions ( P = .01 ) . Within the placebo group , benefit of supplementary vitamin E intake was not found . No benefit was found for use of supplementary vitamin C exclusively or in conjunction with supplementary vitamin E , use of multivitamins , or increased dietary intake of vitamin E or vitamin C. CONCLUSIONS These results indicate an association between supplementary vitamin E intake and angiographically demonstrated reduction in coronary artery lesion progression . Verification from carefully design ed , r and omized , serial arterial imaging end point trials is needed BACKGROUND Epidemiological data suggest that the intake of antioxidants such as alpha-tocopherol ( vitamin E ) and beta-carotene has an inverse correlation with the incidence of coronary heart disease . The results from clinical trials of antioxidant supplementation in people with known coronary heart disease are inconclusive . METHODS We studied the frequency of major coronary events in 1862 men enrolled in the alpha-tocopherol beta-carotene Cancer Prevention Study ( smokers aged between 50 and 69 years ) who had a previous myocardial infa rct ion . In this r and omised , double-blind . placebo-controlled study , men had received dietary supplements of alpha-tocopherol ( 50 mg/day ) , beta-carotene ( 20 mg/day ) , both , or placebo . The median follow-up was 5.3 years . The endpoint of this sub study was the first major coronary event after r and omisation . Analyses were by intention to treat . FINDINGS 424 major coronary events ( non-fatal myocardial infa rct ion and fatal coronary heart disease ) occurred during follow-up . There were no significant differences in the number of major coronary events between any supplementation group and the placebo group ( alpha-tocopherol 94/466 ; beta-carotene 113/461 ; alpha-tocopherol and beta-carotene 123/497 ; placebo 94/438 [ log-rank test , p = 0.25 ] ) . There were significantly more deaths from fatal coronary heart disease in the beta-carotene ( 74/461 , multivariate-adjusted relative risk 1.75 [ 95 % CI 1.16 - 2.64 ] , p = 0.007 ) and combined alpha-tocopherol and beta-carotene groups ( 67/497 , relative risk 1.58 [ 1.05 - 2.40 ] , p = 0.03 ) than in the placebo group ( 39/438 ) , but there was no significant increase in the alpha-tocopherol supplementation group ( 54/466 , relative risk 1.33 [ 0.86 - 2.05 ] , p = 0.20 ) . INTERPRETATION The proportion of major coronary events in men with a previous myocardial infa rct ion who smoke was not decreased with either alpha-tocopherol or beta-carotene supplements . In fact , the risk of fatal coronary heart disease increased in the groups that received either beta-carotene or the combination of alpha-tocopherol and beta-carotene ; there was a non-significant trend of increased deaths in the alpha-tocopherol group . We do not recommend the use of alpha-tocopherol or beta-carotene supplements in this group of patients Carotenoids , found in fruits and vegetables , have the potential to protect against cancer because of their properties , including their functions as precursors to vitamin A and as antioxidants . We examined the associations between intakes of α‐carotene , β‐carotene , β‐cryptoxanthin , lutein/zeaxanthin and lycopene and the risk of invasive epithelial ovarian cancer . The primary data from 10 prospect i ve cohort studies in North America and Europe were analyzed and then pooled . Carotenoid intakes were estimated from a vali date d food frequency question naire administered at baseline in each study . Study ‐specific relative risks ( RR ) were estimated using the Cox proportional hazards model and then combined using a r and om‐effects model . Among 521,911 women , 2,012 cases of ovarian cancer occurred during a follow‐up of 7–22 years across studies . The major carotenoids were not significantly associated with the risk of ovarian cancer . The pooled multivariate RRs ( 95 % confidence intervals ) were 1.00 ( 0.95–1.05 ) for a 600 μg/day increase in α‐carotene intake , 0.96 ( 0.93–1.03 ) for a 2,500 μg/day increase in β‐carotene intake , 0.99 ( 0.97–1.02 ) for a 100 μg/day increase in β‐cryptoxanthin intake , 0.98 ( 0.94–1.03 ) for a 2,500 μg/day increase in lutein/zeaxanthin intake and 1.01 ( 0.97–1.05 ) for a 4,000 μg/day increase in lycopene intake . These associations did not appreciably differ by study ( p‐values , tests for between‐ studies heterogeneity > 0.17 ) . Also , the observed associations did not vary substantially by subgroups of the population or by histological type of ovarian cancer . These results suggest that consumption of the major carotenoids during adulthood does not play a major role in the incidence of ovarian cancer . © 2006 Wiley‐Liss , OBJECTIVES The aim of this study was to assess the efficacy of preoperative and postoperative treatment with n-3 polyunsaturated fatty acids ( PUFAs ) in preventing the occurrence of atrial fibrillation ( AF ) after coronary artery bypass graft surgery ( CABG ) . BACKGROUND Postoperative AF is a common complication of CABG . There is growing clinical evidence that PUFAs have cardiac antiarrhythmic effects . METHODS A total of 160 patients were prospect ively r and omized to a control group ( 81 patients , 13 female , 64.9 + /- 9.1 years ) or PUFAs 2 g/day ( 79 patients , 11 female , 66.2 + /- 8.0 years ) for at least 5 days before elective CABG and until the day of discharge from the hospital . The primary end point was the development of AF in the postoperative period . The secondary end point was the hospital length of stay after surgery . All end points were independently adjudicated by two cardiologists blinded to treatment assignment . RESULTS The clinical and surgical characteristics of the patients in the two groups were similar . Postoperative AF developed in 27 patients of the control group ( 33.3 % ) and in 12 patients of the PUFA group ( 15.2 % ) ( p = 0.013 ) . There was no significant difference in the incidence of nonfatal postoperative complications , and postoperative mortality was similar in the PUFA-treated patients ( 1.3 % ) versus controls ( 2.5 % ) . After CABG , the PUFA patients were hospitalized for significantly fewer days than controls ( 7.3 + /- 2.1 days vs. 8.2 + /- 2.6 days , p = 0.017 ) . CONCLUSIONS This study first demonstrates that PUFA administration during hospitalization in patients undergoing CABG substantially reduced the incidence of postoperative AF ( 54.4 % ) and was associated with a shorter hospital stay Higher intake of fruits , vegetables , and antioxidants may help protect against oxidative damage , thus lowering cancer and cardiovascular disease risk . This Washington County , Maryl and , prospect i ve study examined the association of fruit , vegetable , and antioxidant intake with all-cause , cancer , and cardiovascular disease death . CLUE participants who donated a blood sample in 1974 and 1989 and completed a food frequency question naire in 1989 ( N = 6,151 ) were included in the analysis . Participants were followed to date of death or January 1 , 2002 . Compared with those in the bottom fifth , participants in the highest fifth of fruit and vegetable intake had a lower risk of all-cause ( cases = 910 ; hazard ratio ( HR ) = 0.63 , 95 % confidence interval ( CI ) : 0.51 , 0.78 ; p-trend = 0.0004 ) , cancer ( cases = 307 ; HR = 0.65 , 95 % CI : 0.45 , 0.93 ; p-trend = 0.08 ) , and cardiovascular disease ( cases = 225 ; HR = 0.76 , 95 % CI : 0.54 , 1.06 ; p-trend = 0.15 ) mortality . Higher intake of cruciferous vegetables was associated with lower risk of all-cause mortality ( HR = 0.74 , 95 % CI : 0.60 , 0.91 ; p-trend = 0.04 ) . No statistically significant associations were observed between dietary vitamin C , vitamin E , and beta-carotene intake and mortality . Overall , greater intake of fruits and vegetables was associated with lower risk of all-cause , cancer , and cardiovascular disease death . These findings support the general health recommendation to consume multiple servings of fruits and vegetables ( 5 - 9/day ) This prospect i ve study investigated the relationship between the consumption of fish and intake of long-chain n-3 fatty acids and the risk of coronary heart mortality in 2775 men and 2445 women aged from 30 to 79 years who were free of CHD and had participated in a health examination survey from 1967 to 1972 . In total , 335 men and 163 women died of CHD during a follow-up until the end of 1992 . A dietary history interview method provided data on habitual consumption of fish and other foods over the preceding year at baseline . The intakes of long-chain n-3 fatty acids were calculated on the basis of food composition values of Finnish foods . Higher consumption of fish was associated with a decreased risk of CHD among women , whereas no significant association was seen among men . The relative risk between the highest and the lowest quintile for fish consumption was 1.00 ( 95 % CI 0.70 , 1.43 ; P for trend 0.83 ) for men and 0.59 ( 95 % CI 0.36 , 0.99 ; P for trend 0.02 ) for women in analysis adjusting for age , energy intake , geographical area , BMI , serum cholesterol , blood pressure , smoking , occupation and diabetes ; however , after adjustment for dietary confounders this association was no longer significant . The intake of n-3 fatty acids was not significantly associated with the risk of CHD in either men or women . In conclusion , our results for women are in line with the suggested protective effect of fish consumption against CHD but a similar association was not , however , found in men BACKGROUND R and omized trials have largely failed to support an effect of antioxidant vitamins on the risk of cardiovascular disease ( CVD ) . Few trials have examined interactions among antioxidants , and , to our knowledge , no previous trial has examined the individual effect of ascorbic acid ( vitamin C ) on CVD . METHODS The Women 's Antioxidant Cardiovascular Study tested the effects of ascorbic acid ( 500 mg/d ) , vitamin E ( 600 IU every other day ) , and beta carotene ( 50 mg every other day ) on the combined outcome of myocardial infa rct ion , stroke , coronary revascularization , or CVD death among 8171 female health professionals at increased risk in a 2 x 2 x 2 factorial design . Participants were 40 years or older with a history of CVD or 3 or more CVD risk factors and were followed up for a mean duration of 9.4 years , from 1995 - 1996 to 2005 . RESULTS A total of 1450 women experienced 1 or more CVD outcomes . There was no overall effect of ascorbic acid ( relative risk [ RR ] , 1.02 ; 95 % CI , 0.92 - 1.13 [ P = .71 ] ) , vitamin E ( RR , 0.94 ; 95 % CI , 0.85 - 1.04 [ P = .23 ] ) , or beta carotene ( RR , 1.02 ; 95 % CI , 0.92 - 1.13 [ P = .71 ] ) on the primary combined end point or on the individual secondary outcomes of myocardial infa rct ion , stroke , coronary revascularization , or CVD death . A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior CVD ( RR , 0.89 ; 95 % CI , 0.79 - 1.00 [ P = .04 ] ; P value for interaction , .07 ) . There were no significant interactions between agents for the primary end point , but those r and omized to both active ascorbic acid and vitamin E experienced fewer strokes ( P value for interaction , .03 ) . CONCLUSION There were no overall effects of ascorbic acid , vitamin E , or beta carotene on cardiovascular events among women at high risk for CVD Abstract This evaluation of the Multiple Risk Factor Intervention Trial data base investigated the effects of dietary PUFA on disease outcomes that may relate to polyunsaturated fatty acid ( PUFA ) biochemistry . The Multiple Risk Factor Intervention Trial was a r and omized clinical trial in coronary heart disease ( CHD ) primary prevention involving 12,866 middle-aged men determined to be at high risk of CHD . They were assigned to either a special intervention group or a usual care group and returned to clinics on an annual basis for assessment of risk factor status . Only data on the usual care men ( n = 6,250 ) are presented , since the multi-intervention effects on the special intervention group introduce considerable analytic complexities . Mean PUFA intake estimates were calculated from four dietary recall interviews at baseline and follow-up Years 1 , 2 , and 3 and estimates for PUFA were established using absolute grams , percentage of total kilocalories , and ratios . Proportional hazards regression analysis controlling for age , race and baseline diastolic blood pressure , smoking , high and low density lipoprotein cholesterol levels , and alcohol was used to analyze dietary PUFA intakes on 10.5-year mortality rates . Results were more significant when PUFA were expressed as percentage of total kilocalories . No significant associations with mortality were detected for linoleic acid ( 18:2n-6 ) , the predominant dietary PUFA . Significant inverse associations were observed for linolenic acid ( 18:3n-3 ) on mortality from CHD ( P < 0.04 ) , all cardiovascular diseases ( CVD ) ( P < 0.03 ) , and all cause mortality ( P < 0.02 ) ; the sum of fatty acids primarily derived from fish oils ( 20:5n-3 + 22:5n-3 + 22:6n-3 ) on CHD ( P < 0.02 ) , CVD ( P < 0.006 ) , and all cause ( P < 0.02 ) mortality ; and , the ratio of 18:3n-3 to 18:2n-6 on cancer mortality ( P < 0.05 ) . Analysis using the total n-3 ( 18:3 + 20:5 + 22:5 + 22:6 ) to total n-6 ( 18:2 + 18:4 + 20:4 ) ratio was also significant on cancer mortality ( P < 0.04 ) . These findings support reports that n-3 fatty acids are protective against CVD and suggest that composition of dietary PUFA may influence CVD and cancer rates CONTEXT Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events . Clinical trials have generally failed to confirm benefits , possibly due to their relatively short duration . OBJECTIVE To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer , cancer death , and major cardiovascular events . DESIGN , SETTING , AND PATIENTS A r and omized , double-blind , placebo-controlled international trial ( the initial Heart Outcomes Prevention Evaluation [ HOPE ] trial conducted between December 21 , 1993 , and April 15 , 1999 ) of patients at least 55 years old with vascular disease or diabetes mellitus was extended ( HOPE-The Ongoing Outcomes [ HOPE-TOO ] ) between April 16 , 1999 , and May 26 , 2003 . Of the initial 267 HOPE centers that had enrolled 9541 patients , 174 centers participated in the HOPE-TOO trial . Of 7030 patients enrolled at these centers , 916 were deceased at the beginning of the extension , 1382 refused participation , 3994 continued to take the study intervention , and 738 agreed to passive follow-up . Median duration of follow-up was 7.0 years . INTERVENTION Daily dose of natural source vitamin E ( 400 IU ) or matching placebo . MAIN OUTCOME MEASURES Primary outcomes included cancer incidence , cancer deaths , and major cardiovascular events ( myocardial infa rct ion , stroke , and cardiovascular death ) . Secondary outcomes included heart failure , unstable angina , and revascularizations . RESULTS Among all HOPE patients , there were no significant differences in the primary analysis : for cancer incidence , there were 552 patients ( 11.6 % ) in the vitamin E group vs 586 ( 12.3 % ) in the placebo group ( relative risk [ RR ] , 0.94 ; 95 % confidence interval [ CI ] , 0.84 - 1.06 ; P = .30 ) ; for cancer deaths , 156 ( 3.3 % ) vs 178 ( 3.7 % ) , respectively ( RR , 0.88 ; 95 % CI , 0.71 - 1.09 ; P = .24 ) ; and for major cardiovascular events , 1022 ( 21.5 % ) vs 985 ( 20.6 % ) , respectively ( RR , 1.04 ; 95 % CI , 0.96 - 1.14 ; P = .34 ) . Patients in the vitamin E group had a higher risk of heart failure ( RR , 1.13 ; 95 % CI , 1.01 - 1.26 ; P = .03 ) and hospitalization for heart failure ( RR , 1.21 ; 95 % CI , 1.00 - 1.47 ; P = .045 ) . Similarly , among patients enrolled at the centers participating in the HOPE-TOO trial , there were no differences in cancer incidence , cancer deaths , and major cardiovascular events , but higher rates of heart failure and hospitalizations for heart failure . CONCLUSION In patients with vascular disease or diabetes mellitus , long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure OBJECTIVES This study evaluated whether increased intake of fish oils ( eicosapentaenoic and docosahexaenoic acids ) might reduce the risk of coronary heart disease . BACKGROUND Observational and clinical studies have suggested that increased intake of fish oils , as reflected in plasma levels of fish oils , may reduce the risk of myocardial infa rct ion . METHODS A nested case-control study was conducted among the 14,916 participants in the Physicians ' Health Study with a sample of plasma before r and omization . Each participant with myocardial infa rct ion occurring during the first 5 years of follow-up was matched by smoking status and age with a r and omly chosen control participant who had not developed coronary heart disease . RESULTS Mean levels of fish oils ( with 95 % confidence interval [ CI ] for paired differences and p values ) in case and control participants , expressed as percent of total fatty acids , were , for eicosapentaenoic acid , 0.26 versus 0.25 ( 95 % CI -0.03 to 0.05 , p = 0.70 ) in cholesterol esters and 0.56 versus 0.54 ( 95 % CI -0.04 to 0.09 , p = 0.44 ) in phospholipids , and for docosahexaenoic acid , 0.23 versus 0.24 ( 95 % CI -0.07 to 0.04 , p = 0.64 ) in cholesterol esters and 2.22 versus 2.14 ( 95 % CI -0.10 to 0.27 , p = 0.36 ) in phospholipids . Results adjusted for major cardiovascular risk factors showed a very similar lack of association between fish oil levels and the incidence of myocardial infa rct ion . CONCLUSIONS These results indicate no beneficial effect of increased fish oil consumption on the incidence of a first myocardial infa rct ion . However , the effect of very high levels of fish oils could not be evaluated BACKGROUND The oxidative modification of low-density lipoproteins increases their incorporation into the arterial intima , an essential step in atherogenesis . Although dietary antioxidants , such as vitamin C , carotene , and vitamin E , have been hypothesized to prevent coronary heart disease , prospect i ve epidemiologic data are sparse . METHODS In 1986 , 39,910 U.S. male health professionals 40 to 75 years of age who were free of diagnosed coronary heart disease , diabetes , and hypercholesterolemia completed detailed dietary question naires that assessed their usual intake of vitamin C , carotene , and vitamin E in addition to other nutrients . During four years of follow-up , we documented 667 cases of coronary disease . RESULTS After controlling for age and several coronary risk factors , we observed a lower risk of coronary disease among men with higher intakes of vitamin E ( P for trend = 0.003 ) . For men consuming more than 60 IU per day of vitamin E , the multivariate relative risk was 0.64 ( 95 percent confidence interval , 0.49 to 0.83 ) as compared with those consuming less than 7.5 IU per day . As compared with men who did not take vitamin E supplements , men who took at least 100 IU per day for at least two years had a multivariate relative risk of coronary disease of 0.63 ( 95 percent confidence interval , 0.47 to 0.84 ) . Carotene intake was not associated with a lower risk of coronary disease among those who had never smoked , but it was inversely associated with the risk among current smokers ( relative risk , 0.30 ; 95 percent confidence interval , 0.11 to 0.82 ) and former smokers ( relative risk , 0.60 ; 95 percent confidence interval , 0.38 to 0.94 ) . In contrast , a high intake of vitamin C was not associated with a lower risk of coronary disease . CONCLUSIONS These data do not prove a causal relation , but they provide evidence of an association between a high intake of vitamin E and a lower risk of coronary heart disease in men . Public policy recommendations with regard to the use of vitamin E supplements should await the results of additional studies Tyrosine kinase inhibitors ( TKIs ) have revolutionized the treatment of chronic myeloid leukemia ( CML ) . Although r and omized evidence demonstrates that imatinib ( a commercially available TKI ) prolongs event – free survival in patients with CML , some patients develop imatinib intolerance or resistance . In addition , imatinib is less effective in patients who have progressed to more advanced disease stages , such as accelerated phase and blastic phase CML . For these reasons , 2nd generation TKIs that can inhibit the BCR-ABL protein more effectively or target additional disease mechanisms have been developed . Two such drugs have also been approved for clinical use by the FDA , nilotinib and dasatinib . Resistance to TKI treatment is thought to be mediated through various mechanisms , the most common of which is BCR-ABL1 mutations . Testing for mutations in BCR-ABL1 may predict lack of response to imatinib or may inform the choice between alternative TKIs In a r and omized , placebo-controlled trial , the effects of treatment with fish oil ( eicosapentaenoic acid , 1.08 g/day ) and mustard oil ( alpha-linolenic acid , 2.9 g/day ) were compared for 1 year in the management of 122 patients ( fish oil , group A ) , 120 patients ( mustard oil , group B ) , and 118 patients ( placebo , group C ) with suspected acute myocardial infa rct ion ( AMI ) . Treatments were administered about ( mean ) 18 hours after the symptoms of AMI in all three groups . The extent of cardiac disease , rise in cardiac enzymes , and lipid peroxides were comparable among the groups at entry into the study . After 1 year total cardiac events were significantly less in the fish oil and mustard oil groups compared with the placebo group ( 24.5 % and 28 % vs. 34.7 % , p > 0.01 ) . Nonfatal infa rct ions were also significantly less in the fish oil and mustard oil groups compared with the placebo group ( 13.0 % and 15.0 % vs. 25.4 % , p > 0.05 ) . Total cardiac deaths showed no significant reduction in the mustard oil group ; however , the fish oil group had significantly less cardiac deaths compared with the placebo group ( 11.4 % vs. 22.0 % , p > 0.05 ) . Apart from the decrease in the cardiac event rate , the fish oil and mustard oil groups also showed a significant reduction in total cardiac arrhythmias , left ventricular enlargement , and angina pectoris compared with the placebo group . Reductions in blood lipoproteins in the two intervention groups were modest and do not appear to be the cause of the benefit in the two groups . Diene conjugates showed a significant reduction in the fish oil and mustard oil groups , indicating that a part of the benefit may be caused by the reduction in oxidative stress . The findings of this study suggest that fish oil and mustard oil , possibly due to the presence of n-3 fatty acids , may provide rapid protective effects in patients with AMI . However , a large study is necessary to confirm this suggestion BACKGROUND Although basic research suggests that vitamins may have an important role in the prevention of cardiovascular diseases ( CVD ) , the data from cohort studies and clinical trials are inconclusive . METHODS This prospect i ve cohort study was conducted among 83 639 male physicians residing in the United States who had no history of CVD or cancer . At baseline , data on use of vitamin E , ascorbic acid ( vitamin C ) , and multivitamin supplements were provided by a self-administered question naire . Mortality from CVD and coronary heart disease ( CHD ) was assessed by death certificate review . RESULTS Use of supplements was reported by 29 % of the participants . During a mean follow-up of 5.5 years , 1037 CVD deaths occurred , including 608 CHD deaths . After adjustment for several cardiovascular risk factors , supplement use was not significantly associated with total CVD or CHD mortality . For vitamin E use , the relative risks ( RRs ) were 0.92 ( 95 % confidence interval [ CI ] , 0.70 - 1.21 ) for total CVD mortality and 0.88 ( 95 % CI , 0.61 - 1.27 ) for CHD mortality ; for use of vitamin C , the RRs were 0.88 ( 95 % CI , 0.70 - 1.12 ) for total CVD mortality and 0.86 ( 95 % CI , 0.63 - 1.18 ) for CHD mortality ; and for use of multivitamin supplements , the RRs were 1.07 ( 95 % CI , 0.91 - 1.25 ) for total CVD mortality and 1.02 ( 95 % CI , 0.83 - 1.25 ) for CHD mortality . CONCLUSIONS In this large cohort of apparently healthy US male physicians , self-selected supplementation with vitamin E , vitamin C , or multivitamins was not associated with a significant decrease in total CVD or CHD mortality . Data from ongoing large r and omized trials will be necessary to definitely establish small potential benefits of vitamin supplements on subsequent cardiovascular risk CONTEXT Very-long-chain n-3 polyunsaturated fatty acids ( omega-3 PUFAs ) from fish are thought to reduce risk of sudden death , possibly by reducing susceptibility to cardiac arrhythmia . OBJECTIVE To study the effect of supplemental fish oil vs placebo on ventricular tachyarrhythmia or death . DESIGN , SETTING , AND PATIENTS The Study on Omega-3 Fatty acids and ventricular Arrhythmia ( SOFA ) was a r and omized , parallel , placebo-controlled , double-blind trial conducted at 26 cardiology clinics across Europe . A total of 546 patients with implantable cardioverter-defibrillators ( ICDs ) and prior documented malignant ventricular tachycardia ( VT ) or ventricular fibrillation ( VF ) were enrolled between October 2001 and August 2004 . Patients were r and omly assigned to receive 2 g/d of fish oil ( n = 273 ) or placebo ( n = 273 ) for a median period of 356 days ( range , 14 - 379 days ) . MAIN OUTCOME MEASURE Appropriate ICD intervention for VT or VF , or all-cause death . RESULTS The primary end point occurred in 81 ( 30 % ) patients taking fish oil vs 90 ( 33 % ) patients taking placebo ( hazard ratio [ HR ] , 0.86 ; 95 % confidence interval [ CI ] , 0.64 - 1.16 ; P = .33 ) . In prespecified subgroup analyses , the HR was 0.91 ( 95 % CI , 0.66 - 1.26 ) for fish oil vs placebo in the 411 patients who had experienced VT in the year before the study , and 0.76 ( 95 % CI , 0.52 - 1.11 ) for 332 patients with prior myocardial infa rct ions . CONCLUSION Our findings do not indicate evidence of a strong protective effect of intake of omega-3 PUFAs from fish oil against ventricular arrhythmia in patients with ICDs . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00110838 Diverging results from studies of marine oil supplementation to western diets initiated the undertaking of a double-blind crossover study , with administration to healthy volunteers for 4 weeks of either 10 g of fish oil or 10 g of vegetable oil . Each oil containing approx . 40 % of n-3 and n-6 polyunsaturated fatty acids ( PUFA ) respectively . During the n-3 PUFA period , systolic blood pressure , plasma total lipids , triglycerides and VLDL concentrations fell significantly whereas plasma antithrombin-III ( AT-III ) rose . Cutaneous bleeding time increased significantly . In contrast only AT-III rose during the n-6 PUFA feeding , however , more marked than during the n-3 oil period . It is concluded that a n-3 PUFA oil supplement to the western diet exerts an effect that generally is considered as beneficial in terms of the risk of developing cardiovascular diseases . It is in this respect superior to that of n-6 PUFA , stressing the necessity of a more differentiated approach to advice on dietary PUFA enrichment than presently is exerted BACKGROUND Several epidemiological and experimental studies suggest that n-3 polyunsaturated fatty acids ( PUFA ) can exert favourable effects on atherothrombotic cardiovascular disease , including arrhythmias . We investigated whether n-3 PUFA could improve morbidity and mortality in a large population of patients with symptomatic heart failure of any cause . METHODS We undertook a r and omised , double-blind , placebo-controlled trial in 326 cardiology and 31 internal medicine centres in Italy . We enrolled patients with chronic heart failure of New York Heart Association class II-IV , irrespective of cause and left ventricular ejection fraction , and r and omly assigned them to n-3 PUFA 1 g daily ( n=3494 ) or placebo ( n=3481 ) by a concealed , computerised telephone r and omisation system . Patients were followed up for a median of 3.9 years ( IQR 3.0 - 4.5 ) . Primary endpoints were time to death , and time to death or admission to hospital for cardiovascular reasons . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00336336 . FINDINGS We analysed all r and omised patients . 955 ( 27 % ) patients died from any cause in the n-3 PUFA group and 1014 ( 29 % ) in the placebo group ( adjusted hazard ratio [ HR ] 0.91 [ 95.5 % CI 0.833 - 0.998 ] , p=0.041 ) . 1981 ( 57 % ) patients in the n-3 PUFA group and 2053 ( 59 % ) in the placebo group died or were admitted to hospital for cardiovascular reasons ( adjusted HR 0.92 [ 99 % CI 0.849 - 0.999 ] , p=0.009 ) . In absolute terms , 56 patients needed to be treated for a median duration of 3.9 years to avoid one death or 44 to avoid one event like death or admission to hospital for cardiovascular reasons . In both groups , gastrointestinal disorders were the most frequent adverse reaction ( 96 [ 3 % ] n-3 PUFA group vs 92 [ 3 % ] placebo group ) . INTERPRETATION A simple and safe treatment with n-3 PUFA can provide a small beneficial advantage in terms of mortality and admission to hospital for cardiovascular reasons in patients with heart failure in a context of usual care BACKGROUND Excess cardiovascular mortality has been documented in chronic haemodialysis patients . Oxidative stress is greater in haemodialysis patients with prevalent cardiovascular disease than in those without , suggesting a role for oxidative stress in excess cardiovascular disease in haemodialysis . We investigated the effect of high-dose vitamin E supplementation on cardiovascular disease outcomes in haemodialysis patients with pre-existing cardiovascular disease . METHODS Haemodialysis patients with pre-existing cardiovascular disease ( n=196 ) aged 40 - 75 years at baseline from six dialysis centres were enrolled and r and omised to receive 800 IU/day vitamin E or matching placebo . Patients were followed for a median 519 days . The primary endpoint was a composite variable consisting of : myocardial infa rct ion ( fatal and non-fatal ) , ischaemic stroke , peripheral vascular disease ( excluding the arteriovenous fistula ) , and unstable angina . Secondary outcomes included each of the component outcomes , total mortality , and cardiovascular-disease mortality . FINDINGS A total of 15 ( 16 % ) of the 97 patients assigned to vitamin E and 33 ( 33 % ) of the 99 patients assigned to placebo had a primary endpoint ( relative risk 0.46 [ 95 % CI 0.27 - 0.78 ] , p=0.014 ) . Five ( 5.1 % ) patients assigned to vitamin E and 17 ( 17.2 % ) patients assigned to placebo had myocardial infa rct ion ( 0.3 [ 0.11 - 0.78 ] , p=0.016 ) . No significant differences in other secondary endpoints , cardiovascular disease , or total mortality were detected . INTERPRETATION In haemodialysis patients with prevalent cardiovascular disease , supplementation with 800 IU/day vitamin E reduces composite cardiovascular disease endpoints and myocardial infa rct ion Observational data suggest that diets rich in fruits and vegetables and with high serum levels of antioxidants are associated with decreased incidence and mortality of stroke . We studied the effects of alpha-tocopherol and beta-carotene supplementation . The incidence and mortality of stroke were examined in 28 519 male cigarette smokers aged 50 to 69 years without history of stroke who participated in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study ( ATBC Study ) . The daily supplementation was 50 mg alpha-tocopherol , 20 mg beta-carotene , both , or placebo . The median follow-up was 6.0 years . A total of 1057 men suffered from incident stroke : 85 men had subarachnoid hemorrhage ; 112 , intracerebral hemorrhage ; 807 , cerebral infa rct ion ; and 53 , unspecified stroke . Deaths due to stroke within 3 months numbered 38 , 50 , 65 , and 7 , respectively ( total 160 ) . alpha-Tocopherol supplementation increased the risk of subarachnoid hemorrhage 50 % ( 95 % CI -3 % to 132 % , P=0.07 ) but decreased that of cerebral infa rct ion 14 % ( 95 % CI -25 % to -1 % , P=0.03 ) , whereas beta-carotene supplementation increased the risk of intracerebral hemorrhage 62 % ( 95 % CI 10 % to 136 % , P=0.01 ) . alpha-Tocopherol supplementation also increased the risk of fatal subarachnoid hemorrhage 181 % ( 95 % CI 37 % to 479 % , P=0.01 ) . The overall net effects of either supplementation on the incidence and mortality from total stroke were nonsignificant . alpha-Tocopherol supplementation increases the risk of fatal hemorrhagic strokes but prevents cerebral infa rct ion . The effects may be due to the antiplatelet actions of alpha-tocopherol . beta-Carotene supplementation increases the risk of intracerebral hemorrhage , but no obvious mechanism is available BACKGROUND Oxidized low-density lipoprotein is involved in the pathogenesis of atherosclerosis . In epidemiological studies antioxidants have been inversely related with coronary heart disease . Findings from controlled trials are inconclusive . METHODS We studied the primary preventive effect of vitamin E ( alpha tocopherol ) and beta carotene supplementation on major coronary events in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study , a controlled trial undertaken primarily to examine the effects of these agents on cancer . A total of 27 271 Finnish male smokers aged 50 to 69 years with no history of myocardial infa rct ion were r and omly assigned to receive vitamin E ( 50 mg ) , beta carotene ( 20 mg ) , both agents , or placebo daily for 5 to 8 years ( median , 6.1 years ) . The end point was the first major coronary event , either nonfatal myocardial infa rct ion ( surviving at least 28 days ; n = 1204 ) or fatal coronary heart disease ( n = 907 ) . RESULTS The incidence of primary major coronary events decreased 4 % ( 95 % confidence interval , -12 % to 4 % ) among recipients of vitamin E and increased 1 % ( 95 % confidence interval , -7 % to 10 % ) among recipients of beta carotene compared with the respective nonrecipients . Neither agent affected the incidence of nonfatal myocardial infa rct ion . Supplementation with vitamin E decreased the incidence of fatal coronary heart disease by 8 % ( 95 % confidence interval , -19 % to 5 % ) , but beta carotene had no effect on this end point . CONCLUSIONS Supplementation with a small dose of vitamin E has only marginal effect on the incidence of fatal coronary heart disease in male smokers with no history of myocardial infa rct ion , but no influence on nonfatal myocardial infa rct ion . Supplementation with beta carotene has no primary preventive effect on major coronary events Background : Fruits and vegetables rich in antioxidants have been proposed to reduce the risk of renal cell cancer . However , few prospect i ve studies have examined the intakes of fruits , vegetables , and antioxidant vitamins in relation to the risk of renal cell cancer . Methods : We prospect ively examined the associations between the intakes of fruits , vegetables , vitamins A , C , and E , and carotenoids and risk of renal cell cancer in women and men . We followed 88,759 women in the Nurses ' Health Study from 1980 to 2000 , and 47,828 men in the Health Professionals Follow-up Study from 1986 to 2000 . We assessed dietary intake every 2 to 4 years using a vali date d semiquantitative food frequency question naire . The Cox proportional hazards model was used to estimate study -specific multivariate relative risks ( RR ) , which were pooled using a r and om effects model . Results : A total of 248 ( 132 women and 116 men ) incident renal cell cancer cases were ascertained during 2,316,525 person-years of follow-up . The consumption of fruits and vegetables was associated with a decreased risk of renal cell cancer in men ( multivariate RR , 0.45 ; 95 % CI , 0.25 - 0.81 , for ≥6 servings of fruit and vegetable intake/d versus <3 servings/d ; P test for trend = 0.02 ) , but not in women ( multivariate RR , 1.17 ; 95 % CI , 0.66 - 2.07 , for the same contrast ; P test for trend = 0.25 ; P test for between- studies heterogeneity = 0.02 ) . Intakes of vitamins A and C from food and carotenoids were inversely associated with the risk of renal cell cancer in men only , but we can not exclude the possibility that this was due to other factors in fruit and vegetables . No clear association was observed for vitamin E in women or men . Conclusions : Fruit and vegetable consumption may reduce the risk of renal cell cancer in men . ( Cancer Epidemiol Biomarkers Prev 2006;12(24):2445–52 Both n-3 and n-6 polyunsaturated fats have been suggested to lower blood pressure , an effect ascribed to altered bio synthesis of eicosanoids . To test these hypotheses , we studied blood pressure and eicosanoid production during supplementation of dietary fat for four weeks in 32 men with mild essential hypertension . Supplementation was preceded and followed by four-week run-in and recovery periods . Groups of eight subjects received either 10 ml or 50 ml of fish oil ( 3 or 15 g of n-3 fatty acids ) daily , 50 ml of safflower oil ( 39 g of n-6 fatty acids ) , or 50 ml of a mixture of oils that approximated the types of fat present in the American diet . The bio synthesis of eicosanoids was assessed by the measurement of urinary metabolites . Blood pressure decreased in the men who received the high dose of fish oil ( systolic pressure by a mean of 6.5 mm Hg [ P less than 0.03 ] and diastolic pressure by 4.4 mm Hg [ P less than 0.015 ] ) , but not in the other groups . Although the formation of vasodilatory prostacyclins ( prostagl and ins I2 and I3 ) increased initially , this increase was not maintained as blood pressure fell . The level of thromboxane A2 metabolites fell ; metabolites of thromboxane A3 were detected in the groups receiving fish oil . The formation of prostagl and in E2 increased during supplementation with safflower oil and tended to decrease with fish oil ; no prostagl and in E3 metabolite was detected . Our data indicate that high doses of fish oil can reduce blood pressure in men with essential hypertension . However , the clinical usefulness and safety of fish oil in the treatment of hypertension will require further study |
1,690 | 32,271,952 | AUTHORS ' CONCLUSIONS This study found that epidural corticosteroid injections probably slightly reduced leg pain and disability at short-term follow-up in people with lumbosacral radicular pain .
In addition , no minor or major adverse events were reported at short-term follow-up after epidural corticosteroid injections or placebo injection .
Although the current review identified additional clinical trials , the available evidence still provides only limited support for the use of epidural corticosteroid injections in people with lumbosacral radicular pain as the treatment effects are small , mainly evident at short-term follow-up and may not be considered clinical ly important by patients and clinicians ( i.e. mean difference lower than 10 % ) . | BACKGROUND Lumbosacral radicular pain ( commonly called sciatica ) is a syndrome involving patients who report radiating leg pain .
Epidural corticosteroid injections deliver a corticosteroid dose into the epidural space , with the aim of reducing the local inflammatory process and , consequently , relieving the symptoms of lumbosacral radicular pain .
This Cochrane Review is an up date of a review published in Annals of Internal Medicine in 2012 .
Some placebo-controlled trials have been published recently , which highlights the importance of updating the previous review .
OBJECTIVES To investigate the efficacy and safety of epidural corticosteroid injections compared with placebo injection on pain and disability in patients with lumbosacral radicular pain . | OBJECTIVE This study was carried out to evaluate the therapeutic effect of epidural steroid injection on pseudoclaudication in patients with lumbar degenerative spinal canal stenosis . DESIGN Fifty-three patients who complained of pseudoclaudication of less than 20 m in walking distance were r and omly divided into three groups . Group 1 ( n = 16 ) underwent epidural injection with 8 ml of saline . Group 2 ( n = 18 ) underwent epidural block with 8 ml of 1 % mepivacaine . Group 3 ( n = 19 ) underwent epidural block with a combination of 8 ml of 1 % mepivacaine and 40 mg of methylprednisolone . The criteria of evaluation were as follows : excellent effect , > 100 m in walking distance ; good effect , 20 - 100 m in walking distance ; poor effect , < 20 m in walking distance . RESULTS In group 1 , the numbers of patients who showed a good effect were two ( 12.5 % ) after 1 week , one ( 6.5 % ) after 1 month , and one ( 6.5 % ) after 3 months . In group 2 , the numbers of patients who showed a good or excellent result were 10 ( 55.5 % ) after 1 week , three ( 16.7 % ) after 1 month , and one ( 5.6 % ) after 3 months . In group 3 , the numbers of patients who showed a good or excellent result were 12 ( 63.2 % ) after 1 week , three ( 15.8 % ) after 1 month , and one ( 5.3 % ) after 3 months . There was no significant difference in the effectiveness of treatment between group 2 and group 3 throughout the time course . CONCLUSION The results suggest that epidural steroid injection has no beneficial effect on the pseudoclaudication associated with spinal canal stenosis as compared with epidural block with a local anesthetic alone Study Design . A r and omized , controlled , double-blind trial . Objective . To assess the effectiveness of fluoroscopically directed caudal epidural injections in managing chronic low back and lower extremity pain in patients with disc herniation and radiculitis with local anesthetic with or without steroids . Summary of Background Data . The available literature on the effectiveness of epidural injections in managing chronic low back pain secondary to disc herniation is highly variable . Methods . One hundred twenty patients suffering with low back and lower extremity pain with disc herniation and radiculitis were r and omized to one of the two groups : group I received caudal epidural injections with an injection of local anesthetic , lidocaine 0.5 % , 10 mL ; group II patients received caudal epidural injections with 0.5 % lidocaine , 9 mL , mixed with 1 mL of steroid . The Numeric Rating Scale ( NRS ) , the Oswestry Disability Index 2.0 ( ODI ) , employment status , and opioid intake were utilized with assessment at 3 , 6 , and 12 months posttreatment . Results . The percentage of patients with significant pain relief of 50 % or greater and /or improvement in functional status with 50 % or more reduction in ODI scores was seen in 70 % and 67 % in group I and 77 % and 75 % in group II with average procedures per year of 3.8 ± 1.4 in group I and 3.6 + 1.1 in group II . However , the relief with first and second procedures was significantly higher in the steroid group . The number of injections performed was also higher in local anesthetic group even though overall relief was without any significant difference among the groups . There was no difference among the patients receiving steroids . Conclusion . Caudal epidural injection with local anesthetic with or without steroids might be effective in patients with disc herniation or radiculitis . The present evidence illustrates potential superiority of steroids compared with local anesthetic at 1-year follow-up Objective : To determine the efficacy of epidural corticosteroid injections for sciatica . Methods : Three epidural injections ( two day intervals ) of 2 ml prednisolone acetate ( 50 mg ) or 2 ml isotonic saline were administered to patients with sciatica presumably due to a disk herniation lasting 15–180 days . Self evaluation was the main judgment criterion at day 20 . Patients who recovered or showed marked improvement were considered as success . Pain measured by VAS , the SLR test , Schober ’s test , Dallas pain question naire , and the Rol and -Morris index were evaluated at days 0 , 5 , 20 , and 35 . Only analgesics were authorised , patients requiring non-steroidal anti-inflammatory drugs ( NSAIDs ) before day 20 were considered as failure . Results : 42 patients were included in the control group ( CG ) , 43 in the steroid group ( SG ) . On an intention to treat analysis 15/42 ( 36 % ) in the CG and 22/43 ( 51 % ) in the SG ( p=0.15 ) were considered as success ( difference 15.5 % , 95 % CI ( −5.4 to 36.3 ) ) . Among the 48 failures , 14 patients ( 6 CG , 8 SG ) required NSAIDs , 3 ( 2 CG , 1 SG ) required surgery , and 7 ( 3 CG , 4 SG ) other treatments . On analysis according to protocol , in 74 remaining patients 12/35 ( 34 % ) in the CG and 22/39 ( 56 % ) in the SG ( p=0.057 ) were considered as success ( difference 22.1 % , 95 % CI ( 0.0 to 44.2 ) ) . For all secondary end points intragroup improvement with time was significant , but intergroup differences were not . Conclusion : The efficacy of isotonic saline administered epidurally for sciatica can not be excluded , but epidural steroid injections provide no additional improvement BACKGROUND Epidural injections ( EI ) are the most commonly performed minimally invasive intervention to manage chronic low back pain ( CLBP ) with lumbosacral radicular pain ( LRP ) . Local anesthetic ( LA ) and /or steroids are frequently used injectates for EI and are reported with variable effectiveness . The majority of earlier studies have used either caudal , transforaminal ( TF ) , or undefined interlaminar approaches for EI . The parasaggital interlaminar ( PIL ) approach route is reported to have good ventral epidural spread and comparable effectiveness to the TF route . However , there is a lack of head-to-head comparative effectiveness research of LA with or without steroid for managing CLBP with LRP using a PIL approach . OBJECTIVE To compare the effectiveness of EI of LA alone and LA with steroid using a PIL approach for managing CLBP with LRP . STUDY DESIGN R and omized , double blind , active control one year follow-up study . SETTING Interventional pain management clinic in a tertiary care center in India . METHODS Sixty-nine patients were r and omized to receive fluoroscopic guided EI of either 8 mL of 0.5 % lidocaine ( group L , n = 34 ) or 6 mL of 0.5 % lidocaine mixed with 80 mg ( 2 mL ) of methylprednisolone acetate ( group LS , n = 35 ) . Patients were evaluated for pain intensity using 0 - 10 numerical rating scale ( NRS ) and functional disability using Modified Oswestry Disability Question naire ( MODQ ) at baseline ; and 2 weeks , one , 2 , 3 , 6 , 9 , and 12 months after injection . Patients with inefficacy with the initial injection or response deterioration received an additional injection of the same injectate and dose . Patients were evaluated for achieving effective pain relief ( EPR , i.e. , ≥ 50 % from baseline ) , overall NRS and MODQ , number of injections , and presence of ventral and perineural spread over one year follow-up . Primary outcome was proportion of patients achieving EPR at 3 months . RESULTS A significantly higher proportion of patients achieved EPR at 3 months in group LS [ 30 ( 86 % , 90 % CI 73 % - 93 % ) ] as compared to group L [ 17 ( 50 % , 90 % CI 36 % - 64 % ) ] ( P = 0.02 ) . Similar results were obtained at 6 , 9 , and 12 months , respectively . The probability of achieving EPR was significantly higher in group LS at various time-points during the one year follow-up as compared to group L ( P = 0.01 ) A significant reduction in NRS and improvement in MODQ were observed at all time-points post-intervention compared to baseline ( P < 0.001 ) in both groups . NRS and MODQ scores were significantly lower in group LS as compared to group L at all time intervals post baseline . On average patients in group L received 2.0 ( 0.85 ) and group LS received 1.7 ( 0.71 ) injections annually ( P = 0.07 ) . Ventral epidural spread was comparable in both groups ( 97 % ) . No major complications were encountered in either group ; however , intravascular spread of contrast was noted during 2 injections ( one in each group ) requiring relocation . LIMITATIONS A single center study , lack of documentation of adjuvant therapies like individual analgesic medication , and lack of placebo group . CONCLUSIONS Using a PIL approach and the addition of steroid to LA for EI may provide superior effectiveness in terms of extent and duration of pain relief for managing CLBP with unilateral LRP , even though , local anesthetic alone also was effective . TRIAL REGISTRATION Two controlled studies for a new epidural , perineural , singleshot , selective nerve root injection with a double-needle approach to the anterior epidural space of the lumbar spinal canal are presented . The results were analysed to determine the effectiveness of the new epidural perineural injection technique . The trial comprised two controlled studies on 182 patients . One study compared prospect ively r and omized results of patients with lumbar radicular syndromes who received epidural perineural injections ( n = 47 ) , conventional posterior epidural injections ( n = 40 ) and , as a control group , paravertebral local anaesthetic ( n = 46 ) . A second , prospect i ve , double-blind study compared the effect of epidural perineural injections with triamcinolone ( n = 24 ) and pure saline ( n = 25 ) . Epidural perineural injections were more effective than conventional posterior epidural injections . Both epidural groups had better results than the paravertebral local injection group . Epidural perineural injections with steroids ( 10 mg triamcinolone ) were more effective than saline alone . A systemic steroid effect was excluded by additional intramuscular steroid injections in the saline group . There were no severe complications or side effects in any of the three groups . The studies concluded that single-shot epidural perineural injection is effective in the treatment of lumbar radicular pain . It is a “ one drop only ” therapy to the source of pain Abstract This analysis of the lumbar epidural steroid injections for spinal stenosis multicenter r and omized controlled trial data identifies the degree of and risk factors for cortisol suppression after epidural steroid injections in older adults with spinal stenosis . Four hundred patients aged 50 years and older with back or leg pain and central lumbar spinal stenosis completed baseline demographic and psychosocial measures . Morning serum cortisol levels were measured at baseline and 3 weeks after initial injection . Patients were r and omized to receive epidural injections of either local anesthetic with corticosteroid ( n = 200 ) or local anesthetic only ( n = 200 ) . The specific corticosteroid was chosen at the treating physician 's discretion ( methylprednisolone , betamethasone , triamcinolone , or dexamethasone ) . Thirty-two patients ( 20.3 % ) treated with corticosteroid experienced cortisol reduction at 3 weeks of > 50 % compared with 10 patients ( 6.7 % ) treated with lidocaine only ( adjusted treatment effect = 3.5 , 95 % confidence interval : 1.6 - 7.9 , P = 0.002 ) . The effect on 3-week cortisol changes did not differ by demographic or patient-level characteristics . Those treated with methylprednisolone or triamcinolone had an average 3-week cortisol reduction of 41.0 % ( P = 0.005 ) and 41.6 % ( P < 0.001 ) from baseline , respectively , whereas patients treated with betamethasone or dexamethasone were not significantly different than comparable patients in the lidocaine arm . The higher rates of cortisol suppression at 3 weeks in those receiving epidural corticosteroid injections , particularly with longer-acting insoluble corticosteroid formulations , are consistent with sustained systemic absorption of corticosteroid Background Transforaminal epidural injections with steroids ( TESI ) are used increasingly for patients with sciatica . However there is much debate about their safety and effectiveness . It is important to identify patients that benefit most from TESI and only few trials have yet evaluated the effects in patients with acute sciatica . Methods We describe a prospect i ve , r and omized controlled trial ( RCT ) , with the aim to evaluate the hypothesis that TESI plus Levobupivacaine ( TESI-plus ) added to oral pain medication is more effective compared to pain medication alone or compared to transforaminal injection with a local anesthetic of short duration among patients with acute sciatica . We will recruit a total of 264 patients with sciatica ( < 8 weeks ) caused by a herniated disc , from two clinical sites . Participants are r and omly assigned one of three study groups : 1 ) oral pain medication ( control group ) , 2 ) oral pain medication and TESI-plus ( intervention group one ) , 3 ) oral pain medication and transforaminal epidural injection ( TEI ) with Levobupivaine and saline solution ( intervention group two ) . Primary outcomes are functional status ( Rol and -Morris Disability Question naire ) , pain intensity for both leg and back , ( 100 mm visual analogous scale ( VAS ) ) , and global perceived recovery ( GPR , reported on a 7-point Likert scale , dichotomized into ‘ recovered ’ and ‘ not recovered ’ ) . The secondary outcomes are health-related quality of life ( EQ5D-5 L ) and patient satisfaction ( 7-point Likert scale ) . We will also collect information on healthcare utilization and costs , to perform an economic evaluation . All outcomes are measured at three and six weeks , three and six months after r and omization . We defined a minimal clinical ly relevant difference between groups as a difference between both intervention groups and the control group of 20 points for pain ( 100-point VAS ) , four points for functional status ( 24-point RDQ ) and a 20 % difference on dichotomized GPR ( recovered versus not recovered ) . Discussion A clinical ly relevant outcome in favor of TESI-plus implies that future patients with acute sciatica should be recommended TESI-plus within the first few weeks rather than being treated with pain medication alone in order to relieve pain and improve their functioning . In case of a negative result ( no relevant differences in outcome between the three study arms ) , pain medication will remain the mainstay of treatment in the acute stages of sciatica . Trial registration Dutch National trial register : NTR4457 ( March , 6th , 2014 The management of sciatica due to lumbar nerve root compromise remains controversial , probably because few well-controlled studies of conservative management have been performed . This preliminary study assesses the efficacy of epidural injections of 80 mg triamcinolone acetonide plus 0.5 % procaine hydrochloride in saline , administered via the caudal route , in a double-blind , placebo controlled trial with 1 year follow-up . Twenty-three patients were entered into the study : 12 received treatment and 11 placebo . The active group showed significant pain relief ( P=0.02 ) and a significant increase in mobility ( P=0.01 ) at 4 weeks , which result ed in improved quality of life ( P=0.02 ) . At 1 year , subjective and objective measures improved in both groups . The improvement was greater in the actively treated group , but only the objective assessment ( straight leg raise ) was statistically significant BACKGROUND Although epidural corticosteroid injections are commonly used for sciatica , their efficacy has not been established . METHODS In a r and omized , double-blind trial , we administered up to three epidural injections of methylprednisolone acetate ( 80 mg in 8 ml of isotonic saline ) or isotonic saline ( 1 ml ) to 158 patients with sciatica due to a herniated nucleus pulposus . All patients had Oswestry disability scores higher than 20 ( on a scale of 1 to 100 , with scores of 20 or less indicating minimal disability , and higher scores greater disability ) . RESULTS At three weeks , the Oswestry score had improved by a mean of -8.0 in the methylprednisolone group and -5.5 in the placebo group ( 95 percent confidence interval for the difference , -7.1 to 2.2 ) . Differences in improvements between the groups were not significant , except for improvements in the finger-to-floor distance ( P=0.006 ) and sensory deficits ( P=0.03 ) , which were greater in the methylprednisolone group . After six weeks , the only significant difference was the improvement in leg pain , which was greater in the methylprednisolone group ( P=0.03 ) . After three months , there were no significant differences between the groups . The Oswestry score had improved by a mean of -17.3 in the methylprednisolone group and -15.4 in the placebo group ( 95 percent confidence interval for the difference , -9.3 to 5.4 ) . At 12 months , the cumulative probability of back surgery was 25.8 percent in the methylprednisolone group and 24.8 percent in the placebo group ( P=0.90 ) . CONCLUSIONS Although epidural injections of methylprednisolone may afford short-term improvement in leg pain and sensory deficits in patients with sciatica due to a herniated nucleus pulposus , this treatment offers no significant functional benefit , nor does it reduce the need for surgery BACKGROUND Chronic sciatica can be managed by caudal steroid epidural or by targeted steroid placement during spinal endoscopy . Spinal endoscopy is a new unproven procedure . We aim ed to compare the two pain management techniques and to investigate whether the site of steroid placement within the epidural space was significant . METHODS We r and omized 60 patients with a 6 - 18 months history of sciatica to either targeted epidural local anaesthetic and steroid placement with a spinal endoscope or caudal epidural local anaesthetic and steroid treatment . Pre-treatment and 6-week , 3-month , and 6-month SF-MPQ and HAD scores were recorded . RESULTS No significant differences were found between the groups for any of the measures at any time . However , there were significant differences within both groups compared with pre-treatment values . For the caudal group , significant improvements were found for descriptive pain at 6 months ( P=0.031 ) , VAS at 6 weeks ( P=0.036 ) , 3 months ( P=0.026 ) , and 6 months ( P=0.003 ) , present pain intensity ( PPI ) at 3 months ( P=0.013 ) and 6 months ( P=0.01 ) ; anxiety at 6 weeks ( P=0.008 ) , 3 months ( P=0.004 ) , and 6 months ( P=0.001 ) and depression at 6 months only ( P=0.037 ) . For the epiduroscopy group there were fewer significant changes . PPI was significantly reduced at 6 weeks ( P=0.004 ) and at 6 months ( P=0.02 ) . Anxiety was reduced at 6 months only ( P=0.03 ) . CONCLUSION The targeted placement of epidural steroid onto the affected nerve root causing sciatica does not significantly reduce pain intensity and anxiety and depression compared with untargeted caudal epidural steroid injection . When analysed individually , both techniques benefited patients BACKGROUND CONTEXT Epidural steroid injection is commonly used in patients with chronic low back pain . Applying a mixture of a local anesthetic ( LA ) and steroid using the interlaminar ( IL ) , transforaminal , and caudal techniques is a preferred approach . PURPOSE The present study aims to investigate the efficacy of interlaminar epidural steroid administration in patients with multilevel lumbar disc pathology ( LDP ) and to assess the possible correlation of the procedure 's success with age and body mass index ( BMI ) . STUDY DESIGN A r and omized controlled trial was performed . PATIENT SAMPLE We administered interlaminar epidural steroid to a total of 98 patients with multilevel LDP . OUTCOME MEASURES The visual analog scale ( VAS ) and Oswestry Disability Index ( ODI ) scoring were performed on the study population at pretreatment ( PRT ) , posttreatment , and 1 , 3 , 6 , and 12 PRT months . A possible correlation of BMI and age with the procedure success was evaluated . METHODS The LA group ( Group L , n=50 ) received 10 mL 0.25 % bupivacaine , whereas the steroid+LA group ( Group S , n=48 ) received 10 mL 0.25 % bupivacaine+40 mg methylprednisolone at L4-L5 intervertebral space in prone position under the guidance of C-arm fluoroscopy . RESULTS There was no statistical difference in the PRT VAS and ODI scores between the groups ( p<.05 ) , whereas the VAS and ODI scores at 1 , 3 , 6 , and 12 posttreatment months were higher in Group L , compared with Group S ( p<.05 ) . Age and BMI were not found to be related with the success of the procedure . CONCLUSIONS Our study results showed that the VAS and ODI scores were lower in patients with multilevel LDP receiving steroid , following the administration of IL epidural injection . However , further studies are required to establish a robust conclusion on the dispersion of IL epidural injections in the epidural area and the dose of steroid The value of epidural injections of corticosteroid as an outpatient treatment of sciatica has been hitherto uncertain . An epidural injection of 80 mg methylprednisolone in 10 ml physiological saline was compared with an interspinous injection of 2 ml physiological saline in a double blind fashion amongst 39 out patients . Significant differences of pain relief were seen between the two groups within 2 weeks . This benefit disappeared for six ( 35 % ) patients within 6 months of treatment although 11 ( 65 % ) successfully treated subjects had sustained improvement up to this time . Outpatient epidural injections of corticosteroid are thus a useful short-term means of relieving pain in sciatica but probably have little effect on the long-term natural history of symptoms . Factors associated with a failure to respond to epidural steroid injections are discussed OBJECTIVE To determine the effectiveness and predictors of response to lumbar epidural corticosteroid injections ( ESI ) in patients with sciatica . We performed a 12-month , multicentre , double-blind , r and omized , placebo-controlled , parallel-group trial in four secondary pain-care clinics in the Wessex Region . METHODS Two hundred and twenty-eight patients with a clinical diagnosis of unilateral sciatica of 1 - 18 months ' duration were r and omized to either three lumbar ESIs of triamcinolone acetonide or interligamentous saline injections at intervals of 3 weeks . The main outcome measure was the Oswestry low back pain disability question naire ( ODQ ) . RESULTS At 3 weeks , the ESI group demonstrated a transient benefit over the placebo group ( patients achieving a 75 % improvement in ODQ , 12.5 vs 3.7 % ; number needed to treat , 11.4 ) . No benefit was demonstrated from 6 to 52 weeks . ESIs did not improve physical function , hasten return to work or reduce the need for surgery . There was no benefit of repeated ESIs over single injection . No clinical predictors of response were found . At the end of the study the majority of patients still had significant pain and disability regardless of intervention . CONCLUSIONS In this pragmatic study , ESIs offered transient benefit in symptoms at 3 weeks in patients with sciatica , but no sustained benefits in terms of pain , function or need for surgery . Sciatica is a chronic condition requiring a multidisciplinary approach . To fully investigate the value of ESIs , they need to be evaluated as part of a multidisciplinary approach BACKGROUND In a previous prospect i ve , r and omized , controlled , double-blinded study on the effect of nerve root blocks on the need for operative treatment of lumbar radicular pain , we found that injections of corticosteroids were more effective than bupivacaine for up to thirteen to twenty-eight months . We performed a minimum five-year followup of those patients who had avoided surgery . METHODS All of the patients were considered to be operative c and i date s by the treating surgeon , and all had initially requested operative intervention . They had then been r and omized to be treated with a selective nerve-root block with either bupivacaine or bupivacaine and betamethasone . Both the treating physician and the patient were blinded to the type of medication . Of fifty-five r and omized patients , twenty-nine avoided an operation in the original study . Twenty-one of those twenty-nine patients were reevaluated with a follow-up question naire at a minimum of five years after the initial block . RESULTS Seventeen of the twenty-one patients still had not had operative intervention . There was no difference between the group treated with bupivacaine alone and the group treated with bupivacaine and betamethasone with regard to the avoidance of surgery for five years . At the five-year follow-up evaluation , all of the patients who had avoided operative treatment had significant decreases in neurological symptoms and back pain compared with the baseline values . CONCLUSIONS The majority of patients with lumbar radicular pain who avoid an operation for at least one year after receiving a nerve root injection with bupivacaine alone or in combination with betamethasone will continue to avoid operative intervention for a minimum of five years Background and Objectives : Serious adverse events related to particulate steroids have curtailed the use of transforaminal epidural steroid injections for radicular pain . Dexamethasone has been proposed as an alternative . We investigated the efficacy , dose-response profile , and safety of 3 doses of epidural dexamethasone . Methods : A prospect i ve , r and omized , double-blind , dose-ranging design was used . A total of 98 subjects were r and omized to transforaminal epidural dexamethasone 4 mg ( n = 33 ) , 8 mg ( n = 33 ) , or 12 mg ( n = 32 ) . The primary outcome measure for this study was reduction in radicular pain according to the visual analog scale from baseline , with 30 % reduction or higher considered clinical ly meaningful . Secondary measures included the Oswestry Low Back Disability Scale , Subject Global Impression of Change , Subject Global Satisfaction Scale , and adverse events . Outcomes were assessed at 1 , 4 , 8 , and 12 weeks after injection . Outcome measures , sample size , and statistical analysis were defined before enrollment . Results : Mean radicular pain according to the visual analog scale compared with baseline was reduced 41.7 % , 33.5 % , and 26.6 % at 4 , 8 , and 12 weeks , respectively , after injection . Oswestry disability ratings declined from " moderate " at baseline to " minimal " at 4 , 8 , and 12 weeks after injection . There was no statistical difference between groups for either measure ( all P values < 0.05 , Bonferroni-corrected ) . Parallel effects were observed in " impression of change " and " satisfaction " measures . No serious adverse events were noted . Conclusions : Transforaminal epidural dexamethasone provides statistically significant and clinical ly meaningful improvement in radicular pain at 12 weeks after injection , with parallel improvements in disability , impression of change , and satisfaction measures . There was no difference in efficacy for dexamethasone 4 mg compared with 8 or 12 mg . The optimal dose of epidural dexamethasone may be lower than 4 mg , further increasing the long-term safety and tolerability of this treatment . Current data are reassuring with regard to the safety of dexamethasone for transforaminal epidural steroid injection Background Corticosteroid injections into the intra-articular zygapophysial ( z-joints ) are frequently used to treat this cause of low back pain . No studies have been done on the efficacy of intra-articular corticosteroids in those with z-joint pain confirmed by dual comparative medial branch blocks . Objective The aim of the study was to determine whether an injection of a corticosteroid into lumbar z-joints is effective in reducing pain and the need for radiofrequency neurotomy . Methods This is a double-blind , prospect i ve , r and omized , placebo-controlled trial . The study was conducted in Academic Medical Center . Twenty-eight subjects with z-joint pain confirmed by medial branch blocks were included in the study . Subjects with confirmed z-joint pain via dual comparative medial branch block were r and omized to receive either intra-articular corticosteroid ( triamcinolone 20 mg ) or saline via fluoroscopic guided injection . Results No statistically significant difference in the need for radiofrequency neurotomy ( radiofrequency neurotomy ) between the groups , with 75 % ( 95 % confidence interval = 50.5%–99.5 % ) of the saline group vs. 91 % ( 95 % confidence interval = 62.3%–100 % ) of the corticosteroid group receiving radiofrequency neurotomy . There is no difference in mean time to radiofrequency neurotomy between saline ( 6.1 wks ) and corticosteroid ( 6.5 wks ) groups . There is a need for radiofrequency neurotomy . Conclusions Corticosteroid injections into the lumbar z-joints were not effective in reducing the need for radiofrequency neurotomy of the medial branches in those with z-joint pain confirmed by dual comparative medial branch blocks Objective To evaluate whether an epidural steroid injection or gabapentin is a better treatment for lumbosacral radiculopathy . Design A multicenter r and omized study conducted between 2011 and 2014 . Computer generated r and omization was stratified by site . Patients and evaluating physicians were blinded to treatment outcomes . Setting s Eight military , Veterans Administration , and civilian hospitals . Participants 145 people with lumbosacral radicular pain secondary to herniated disc or spinal stenosis for less than four years in duration and in whom leg pain is as severe or more severe than back pain . Interventions Participants received either epidural steroid injection plus placebo pills or sham injection plus gabapentin . Main outcome measures Average leg pain one and three months after the injection on a 0 - 10 numerical rating scale . A positive outcome was defined as a ≥2 point decrease in leg pain coupled with a positive global perceived effect . All patients had one month follow-up visits ; patients whose condition improved remained blinded for their three month visit . Results There were no significant differences for the primary outcome measure at one month ( mean pain score 3.3 ( SD 2.6 ) and mean change from baseline −2.2 ( SD 2.4 ) in epidural steroid injection group versus 3.7 ( SD 2.6 ) and −1.7 ( SD 2.6 ) in gabapentin group ; adjusted difference 0.4 , 95 % confidence interval −0.3 to 1.2 ; P=0.25 ) and three months ( mean pain score 3.4 ( SD 2.7 ) and mean change from baseline −2.0 ( SD 2.6 ) versus 3.7 ( SD 2.8 ) and −1.6 ( SD 2.7 ) , respectively ; adjusted difference 0.3 , −0.5 to 1.2 ; P=0.43 ) . Among secondary outcomes , one month after treatment those who received epidural steroid injection had greater reductions in worst leg pain ( −3.0 , SD 2.8 ) than those treated with gabapentin ( −2.0 , SD 2.9 ; P=0.04 ) and were more likely to experience a positive successful outcome ( 66 % v 46 % ; number needed to treat=5.0 , 95 % confidence interval 2.8 to 27.0 ; P=0.02 ) . At three months , there were no significant differences between treatments . Conclusions Although epidural steroid injection might provide greater benefit than gabapentin for some outcome measures , the differences are modest and are transient for most people . Trial registration Clinical Trials.gov Identifier : NCT01495923 Study Design . Prospect i ve , double-blind , reference-controlled , investigator-initiated , single center . Objective . To evaluate the efficacy of Autologous Conditioned Serum ( ACS ; Orthokine ) for the treatment of lumbar radicular compression in comparison to triamcinolone . Summary of Background Data . Evidence from animal studies indicates that cytokines such as interleukin-1 play a decisive role in the pathophysiology of lumbar radiculopathy . ACS is enriched in the interleukin-1 receptor antagonist and other anti-inflammatory cytokines . Methods . Thirty-two patients were treated by epidural perineural injections with ACS ; 27 patients were treated with 5 mg triamcinolone and 25 patients with 10 mg triamcinolone . Treatment was applied once per week for 3 consecutive weeks and followed for 6 months . The Visual Analogue Scale ( VAS ) of low back pain was the primary outcome measure . The Oswestry Disability Index ( ODI ) was the secondary endpoint of the study . All statistical analyses were performed in an exploratory manner using SAS for Windows , version 8.2 , on a personal computer . Descriptive statistics were calculated for the VAS and ODI by treatment group and time point . The data were su bmi tted to a repeated- measurements analysis of variance with effects on treatment group , time , and treatment group-by-time interaction . Results . Patients with lumbar back pain who were treated with ACS or the 2 triamcinolone concentrations showed a clinical ly remarkable and statistically significant reduction in pain and disability , as measured by patient administered outcome measurements . From Week 12 to the final evaluation at Week 22 , injections with ACS showed a consistent pattern of superiority over both triamcinolone groups with regard to the VAS score for pain , but statistical significance was observed only at Week 22 in direct comparison to the triamcinolone 5 group . However , there was no statistically significant difference between the 2 triamcinolone dosages during the 6 months of the study . Conclusion . ACS is an encouraging treatment option for patients with unilateral lumbar radicular compression . The decrease in pain was pronounced , clinical ly remarkable , and potentially superior to steroid injection Four treatment regimens for patients with specified combinations of low back pain and sciatica were evaluated . The largest group studied had low back pain with limited straight-leg raising ( SLR ) and in them the beneficial effect of manipulation in hastening pain relief was highly significant . In similar patients without limitation of SLR , the effect was of borderline significance . In all the other groups , treated patients also recovered more quickly than their controls . Traction , for patients with low back pain and sciatica , and epidural injections when a root palsy was present also produced some significant pain relief . The effect of sclerosants for back pain was less clear Study Design . A r and omized , double-blind controlled trial . Objectives . To determine the treatment effect of corticosteroids in periradicular infiltration for chronic radicular pain . We also examined prognostic factors in relation to the outcome of the procedure . Summary of Background Data . Various studies have examined the therapeutic value of periradicular infiltration using treatment agents consisting of local anesthetic and corticosteroids for radicular pain , secondary to lumbar disc herniation and spinal stenosis . There is currently no r and omized trial to determine the efficacy of a single injection of corticosteroids for chronic radicular pain . Methods . Eligible patients with radicular pain who had unilateral symptoms who failed conservative management were r and omized for a single injection with bupivacaine and methylprednisolone or bupivacaine only . Outcome measures included the Oswestry Disability Index , visual analogue score for back pain and leg pain , claudication walking distance , and the patient 's subjective level of satisfaction of the outcome . Results . We recruited 43 patients in the bupivacaine and methylprednisolone group and 43 patients in the bupivacaine only group . The follow-up rate is 100 % . Five patients had early termination of the trial for discectomy and further root block . There is no statistically significant difference in the outcome measures between the groups at 3 months ( change of the Oswestry Disability Index [ P = 0.68 ] , change in visual analogue score [ back pain , P = 0.68 ; leg pain , P = 0.94 ] , change in walking distance [ P = 0.7 ] ) . Duration of symptoms has a statistically significant negative association with the change in Oswestry Disability Index ( P = 0.03 ) . Conclusion . Clinical improvement occurred in both groups of patients . Corticosteroids did not provide additional benefit BACKGROUND Although epidural steroids are commonly used for conservative management of sciatica , controversies exist regarding optimal approach , type and dose of steroids , volume of injectate and frequency of administration . This r and omized comparative blinded study was undertaken to compare the efficacy of caudal methylprednisolone acetate with triamcinolone acetonide and dexamethasone acetate , for pain relief for sciatica associated with lumbar-disk herniations . METHODS A Total of 163 patients with radicular pain due to lumbar-disk herniations , between 27 - 70 years of age were r and omly divided into four groups : three were given epidural steroid injection therapy ( methylprednisolone acetate , triamcinolone acetonide and betamethasone acetate ) with bupivacaine ; one group received bupivacaine alone via caudal approach . Injections were repeated every three weeks till a total of 210 mg of methylprednisolone ( and equivalent ) or three injections . Pain relief , disability and activity levels were assessed at 3 , 6 , 9 and 12 weeks interval . RESULT Pain relief was present in all four groups by three weeks with no difference between the groups ( p=0.006 ; 0.005 ; 0.0045 ; 0.005 respectively to baseline ) . By the 6 and 12 week , the three steroid groups had significant pain relief ( p<0.001 ) . Among these , both methylprednisolone and triamcinolone groups showed greater improvement in the finger-to-floor distance ( p=0.006 ) . A smaller proportion of patients in this group had residual sensory deficits ( p=0.03 ) as compared to dexamethasone but difference was statistically insignificant . Overall pain relief was significantly better at all follow-up evaluations in the steroid group than in the control group ( p<0.001 at all evaluations ) . CONCLUSION Short-term improvement in leg pain and sensory deficits was observed in patients with sciatica due to a herniated nucleus pulposus with both epidural bupivacaine and steroids . All long-acting steroids had no statistically significant difference between their efficacy in pain relief but methylprednisolone and triamcinolone were more effective by the second injection as compared to dexamethasone which required a third injection in a significant number of cases . Differences between methylprednisolone and triamcinolone were insignificant . Complications were negligible and temporary BACKGROUND The pathophysiology of lumbar radicular pain is the subject of ongoing research , with a reported prevalence of sciatica or radiculitis ranging from 1.2 % to 43 % . Among the numerous non-surgical interventions available , epidural injections are the most commonly performed interventions in the United States in managing chronic low back and lower extremity pain . STUDY DESIGN A r and omized , double-blind , controlled trial . SETTING An interventional pain management practice , a specialty referral center , a private practice setting in the United States . OBJECTIVE To evaluate the effectiveness of lumbar interlaminar epidural injections with local anesthetic , with or without steroids , in managing chronic low back and lower extremity pain secondary to disc herniation or radiculitis in providing effective and long-lasting pain relief . METHODS Patients were assigned to one of 2 groups with local anesthetic only or with local anesthetic mixed with non-particulate betamethasone . R and omization was performed by computer-generated r and om allocations sequence by simple r and omization . Seventy patients were included in this analysis . OUTCOMES ASSESSMENT Patient outcomes were measured at baseline , 3 , 6 , and 12 months post-treatment with the Numeric Rating Scale ( NRS ) , the Oswestry Disability Index 2.0 ( ODI ) , employment status , and opioid intake . Decrease of > or = 50 % of NRS scores and Oswestry scores were considered significant . RESULTS Significant pain relief ( > or = 50 % ) was seen at 12 months in 74 % of patients in Group I and 86 % in Group II , and 69 % and 83 % in ODI scores respectively . Significant differences were noted in pain relief characteristics at 6 months between Group I and Group II ( p = 0.001 ) and functional status improvement was significantly better in Group II at 6 months and 12 months ( p = 0.019 and 0.045 ) . The overall average procedures per year were 4.3 in Group I and 4.2 in Group II with an average total relief per year of 42.2 + /- 10.5 weeks in Group I and 41.4 + /- 11.0 weeks in Group II over a period of 52 weeks in the successful group . LIMITATIONS The study limitations include the lack of a placebo group and the fact that this is a preliminary report of 35 patients in each group . CONCLUSION Overall , 74 % of patients in Group I without steroids and 86 % in Group II with steroids with lumbar disc herniation or radiculitis might benefit from lumbar interlaminar epidural injections Purpose In low back pain ( LBP ) patients , those with radiating leg pain or sciatica have poorer pain and disability outcomes . Few studies have assessed the effect of leg pain on health care use and quality of life . Methods Prospect i ve cohort study of 1,581 UK LBP primary care consulters . Back pain , employment , health care utilisation , and quality of life ( EQ-5D ) data were collected at baseline , 6 and 12 months . At baseline , patients were classified as reporting ( 1 ) LBP only , ( 2 ) LBP and leg pain above the knee only ( LBP + AK ) or ( 3 ) LBP and leg pain extending below the knee ( LBP + BK ) . Results Self-reported leg pain was common ; at baseline 645 ( 41 % ) reported LBP only , 392 ( 25 % ) reported LBP + AK and 544 ( 34 % ) reported LBP + BK . Patients with LBP + BK , compared to those with LBP only , were significantly more likely to be unemployed , take time off work , consult their family doctor , receive physical therapy , or be referred to other health care practitioners . There were statistically significant decrements in EQ-5D scores for LBP + AK compared to LBP only , and for LBP + BK compared to LBP + AK ( p ≤ 0.05 for all comparisons ) . Conclusions Patients with self-reported leg pain below the knee utilise more health care are more likely to be unemployed and have poorer quality of life than those with LBP only 12 months following primary care consultation . The presence of leg pain warrants early identification in primary care to explore if targeted interventions can reduce the impact and consequences of leg pain Study Design . A r and omized , double-blind trial was conducted . Objectives . To test the efficacy of periradicular corticosteroid injection for sciatica . Summary of Background Data . The efficacy of epidural corticosteroids for sciatica is controversial . Periradicular infiltration is a targeted technique , but there are no r and omized controlled trials of its efficacy . Methods . In this study 160 consecutive , eligible patients with sciatica who had unilateral symptoms of 1 to 6 months duration , and who never underwent surgery were r and omized for double-blind injection with methylprednisolone bupivacaine combination or saline . Objective and self-reported outcome parameters and costs were recorded at baseline , at 2 and 4 weeks , at 3 and 6 months , and at 1 year . Results . Recovery was better in the steroid group at 2 weeks for leg pain ( P = 0.02 ) , straight leg raising ( P = 0.03 ) , lumbar flexion ( P = 0.05 ) , and patient satisfaction ( P = 0.03 ) . Back pain was significantly lower in the saline group at 3 and 6 months ( P = 0.03 and 0.002 , respectively ) , and leg pain at 6 months ( 13.5 , P = 0.02 ) . Sick leaves and medical costs were similar for both treatments , except for cost of therapy visits and drugs at 4 weeks , which were in favor of the steroid injection ( P = 0.05 and 0.005 , respectively ) . By 1 year , 18 patients in the steroid group and 15 in the saline group underwent surgery . Conclusions . Improvement during the follow-up period was found in both the methylprednisolone and saline groups . The combination of methylprednisolone and bupivacaine seems to have a short-term effect , but at 3 and 6 months , the steroid group seems to experience a “ rebound ” phenomenon OBJECTIVE To evaluate the pattern and flow of epidural contrast in fluoroscopically guided lumbar interlaminar steroid injections . DESIGN AND METHODS A prospect i ve case series of 25 ( twenty-five ) consecutive patients receiving 25 ( twenty-five ) injections . Patients had either lumbar spinal stenosis ( LSS ) or herniated nucleus pulposus ( HNP ) . All patients received their injection using a loss of resistance technique . Once the epidural space was felt localized 0.5 mL of Isovue contrast was injected to confirm accurate needle placement . If in the epidural space , another 4.5 mL was injected for a total of 5 mL contrast media . Both AP and lateral radiographs were obtained and review ed by a physician trained in fluoroscopic injections for review of the contrast pattern . Patterns recorded were Unilateral , Bilateral , Ventral or Dorsal . The dorsal flow was also characterized as being cephalad or caudad and the number of lumbar intervertebral levels of flow were recorded as well . RESULTS Dorsal contrast flow occurred in all 25 injections . Thirty-six percent ( 9 out of 25 ) result ed in ventral spread of contrast . Eighty-four percent ( 21 out of 25 ) of the injections had flow of contrast unilaterally and 16 % ( 4 out of 25 ) was bilateral . The mean number of levels of flow of contrast cephalad from the injection site was 1.28 and caudally 0.88 . There was a significant difference in more cephalad than caudal contrast flow ( P = 0.004 ) CONCLUSION Thirty six percent of the injections observed in the study revealed ventral contrast flow . Bilateral contrast flow occurred in 16 % of the injections . Caudad contrast flow is less than cephalad . The observed contrast flows need to be studied clinical ly to determine if this can affect clinical outcome Objective To determine the efficacy of fluoroscopic guided transforaminal steroid versus interlaminar epidural steroid versus caudal steroid . Material and method A total of 90 patients were studied who had complains of low back pain with radiculopathy and MRI evidence of disc prolapse . Out of this group , patients were r and omly assigned to three groups each having 30 patients . First group received transforaminal steroid injection , second group received caudal steroid injection , and third group received epidural steroid . All patients were followed up for 12 months , and the results were compared using change in Visual Analogue Scale score and Oswestry Disability Index ( OSD ) . Results The change in pain scores was statistically different at 1- and 6-month interval such that a higher change was observed by transforaminal route as compared to the other two . There was no difference in change of scores between interlaminar and caudal routes . For OSD , a greater change was seen in transforminal at all times as compared to the other two . There was no difference in change of scores between interlaminar and caudal routes at any time of assessment . Conclusion In current study , transforaminal steroid injection group has better symptomatic improvement for both short and long term as compared to interlaminar and caudal steroid injection group BACKGROUND While low back pain is the number one cause of disability in the United States , lumbar spinal stenosis along with intervertebral disc herniation and degenerative spondylolisthesis is one of the 3 most common diagnosis of low back and leg pain for which surgery is performed . Numerous modalities of treatments including drug therapy and complex surgical fusions have been recommended for treatment of central spinal stenosis . Epidural injections are one of the commonly performed nonsurgical interventions in managing central spinal stenosis ; however , there has been paucity of literature in reference to efficacy of epidural injections in managing central spinal stenosis with lumbar interlaminar epidural injections . STUDY DESIGN A r and omized , double-blind , active controlled trial . SETTING Private interventional pain management practice and specialty referral center in the United States . OBJECTIVE To assess the effectiveness of lumbar interlaminar epidural injections with or without steroids in providing effective and long-lasting pain relief with improvement in functional status for the management of chronic low back and lower extremity pain related to lumbar central spinal stenosis . METHODS A r and omized , double-blind , active-control trial was design ed with the inclusion of 120 patients assigned to 2 groups . Group I patients received lumbar interlaminar epidural injections of local anesthetic ( lidocaine 0.5 % ) 6 mL , whereas Group II received lumbar interlaminar epidural injections with local anesthetic ( lidocaine 0.5 % ) 5 mL mixed with 1 mL of steroids and 6 mg of betamethasone . OUTCOMES ASSESSMENT Outcomes were assessed utilizing the numeric pain rating scale ( NRS ) and Oswestry Disability Index ( ODI ) at 3 , 6 , 12 , 18 , and 24 months post treatment . The primary outcome measure was significant improvement , defined as 50 % improvement in pain and disability scores . RESULTS Significant relief and functional status improvement was seen in 72 % and 73 % of patients in Groups I and II at the end of 2 years considering all participants ; however , this was 84 % and 85 % in the successful group . Overall significant improvement was achieved for 65.7 ± 37.3 weeks in Group 1 and 68.9 ± 37.7 weeks in Group II at the end of 2 years when all participants were considered ; whereas , this was 77 ± 27.8 weeks and 77.9 ± 30.2 weeks when they were separated into successful categories . The average number of procedures per patient was 5 to 6 in both groups . LIMITATIONS Limitations of this trial include lack of placebo control group and treatment of patients with multiple procedures over a period of 2 years . CONCLUSION Lumbar interlaminar epidural injections of local anesthetic with or without steroids provide relief in a significant proportion of patients with lumbar central spinal stenosis . CLINICAL TRIAL NCT00681447 OBJECTIVE The primary objective of this study was to compare the efficacy of local injection of a local anesthetic with a glucocorticoid versus a local anesthetic with saline to treat low back pain due to lumbosacral transitional vertebras ( LSTV ) with a pseudoarticulation . METHODS A r and omized placebo-controlled double-blind study was conducted in patients with unilateral low back pain ascribed clinical ly to LSTV . Patients were r and omized to lidocaine plus saline ( LS group ) or lidocaine plus cortivazol ( LC group ) injected locally under computed tomography guidance . The primary outcome measure was the 24-hour mean visual analog scale ( VAS ) score for low back pain 4 weeks after the injection . RESULTS Of 16 r and omized patients , 15 were included in the analysis , 8 in the LS group and 7 in the LC group . The mean VAS pain score at week 4 was not significantly different between the two groups . In the two groups pooled , the mean VAS pain score decreased significantly from baseline to week 4 , from 5.52±0.99 to 3.86±2.55 ( P≤0.05 ) . The difference remained significant at week 12 . Significant improvements occurred in the EIFEL disability index and items of the Dallas Pain Question naire . No adverse events were recorded . CONCLUSION In patients with chronic low back pain consistent with a symptomatic LSTV type II or IV in the Castellvi classification , a local injection of lidocaine with or without cortivazol may provide sustained improvements in pain and function . The underlying mechanism is unclear OBJECTIVE To determine the overall long-term effectiveness of treatment with epidural corticosteroid injections for lumbar central spinal stenosis and the effect of repeat injections , including crossover injections , on outcomes through 12 months . DESIGN Multicenter , double-blind , r and omized controlled trial comparing epidural injections of corticosteroid plus lidocaine versus lidocaine alone . SETTING Sixteen clinical sites . PARTICIPANTS Participants with imaging-confirmed lumbar central spinal stenosis ( N=400 ) . INTERVENTIONS Participants were r and omized to receive either epidural injections with corticosteroid plus lidocaine or lidocaine alone with the option of blinded crossover after 6 weeks to receive the alternate treatment . Participants could receive 1 to 2 injections from 0 to 6 weeks and up to 2 injections from 6 to 12 weeks . After 12 weeks , participants received usual care . MAIN OUTCOME MEASURES Primary outcomes were the Rol and -Morris Disability Question naire ( RDQ ) ( range , 0 - 24 , where higher scores indicate greater disability ) and leg pain intensity ( range , 0 [ no pain ] to 10 [ pain as bad as you can imagine ] ) . Secondary outcomes included opioid use , spine surgery , and crossover rates . RESULTS At 12 months , both treatment groups maintained initial observed improvements , with no significant differences between groups on the RDQ ( adjusted mean difference , -0.4 ; 95 % confidence interval [ CI ] , -1.6 to 0.9 ; P=.55 ) , leg pain ( adjusted mean difference , 0.1 ; 95 % CI , -0.5 to 0.7 ; P=.75 ) , opioid use ( corticosteroid plus lidocaine : 41.4 % vs lidocaine alone : 36.3 % ; P=.41 ) , or spine surgery ( corticosteroid plus lidocaine : 16.8 % vs lidocaine alone : 11.8 % ; P=.22 ) . Fewer participants r and omized to corticosteroid plus lidocaine ( 30 % , n=60 ) versus lidocaine alone ( 45 % , n=90 ) crossed over after 6 weeks ( P=.003 ) . Among participants who crossed over at 6 weeks , the 6- to 12-week RDQ change did not differ between the 2 r and omized treatment groups ( adjusted mean difference , -1.0 ; 95 % CI , -2.6 to 0.7 ; P=.24 ) . In both groups , participants crossing over at 6 weeks had worse 12-month trajectories compared with participants who did not choose to crossover . CONCLUSIONS For lumbar spinal stenosis symptoms , epidural injections of corticosteroid plus lidocaine offered no benefits from 6 weeks to 12 months beyond that of injections of lidocaine alone in terms of self-reported pain and function or reduction in use of opioids and spine surgery . In patients with improved pain and function 6 weeks after initial injection , these outcomes were maintained at 12 months . However , the trajectories of pain and function outcomes after 3 weeks did not differ by injectate type . Repeated injections of either type offered no additional long-term benefit if injections in the first 6 weeks did not improve pain Objective To assess the efficacy of caudal epidural steroid or saline injection in chronic lumbar radiculopathy in the short ( 6 weeks ) , intermediate ( 12 weeks ) , and long term ( 52 weeks ) . Design Multicentre , blinded , r and omised controlled trial . Setting Outpatient multidisciplinary back clinics of five Norwegian hospitals . Participants Between October 2005 and February 2009 , 461 patients assessed for inclusion ( presenting with lumbar radiculopathy > 12 weeks ) . 328 patients excluded for cauda equina syndrome , severe paresis , severe pain , previous spinal injection or surgery , deformity , pregnancy , ongoing breast feeding , warfarin therapy , ongoing treatment with non-steroidal anti-inflammatory drugs , body mass index > 30 , poorly controlled psychiatric conditions with possible secondary gain , and severe comorbidity . Interventions Subcutaneous sham injections of 2 mL 0.9 % saline , caudal epidural injections of 30 mL 0.9 % saline , and caudal epidural injections of 40 mg triamcinolone acetonide in 29 mL 0.9 % saline . Participants received two injections with a two week interval . Main outcome measures Primary : Oswestry disability index scores . Secondary : European quality of life measure , visual analogue scale scores for low back pain and for leg pain . Results Power calculations required the inclusion of 41 patients per group . We did not allocate 17 of 133 eligible patients because their symptoms improved before r and omisation . All groups improved after the interventions , but we found no statistical or clinical differences between the groups over time . For the sham group ( n=40 ) , estimated change in the Oswestry disability index from the adjusted baseline value was −4.7 ( 95 % confidence intervals −0.6 to −8.8 ) at 6 weeks , −11.4 ( −6.3 to −14.5 ) at 12 weeks , and −14.3 ( −10.0 to −18.7 ) at 52 weeks . For the epidural saline intervention group ( n=39 ) compared with the sham group , differences in primary outcome were −0.5 ( −6.3 to 5.4 ) at 6 weeks , 1.4 ( −4.5 to 7.2 ) at 12 weeks , and −1.9 ( −8.0 to 4.3 ) at 52 weeks ; for the epidural steroid group ( n=37 ) , corresponding differences were −2.9 ( −8.7 to 3.0 ) , 4.0 ( −1.9 to 9.9 ) , and 1.9 ( −4.2 to 8.0 ) . Analysis adjusted for duration of leg pain , back pain , and sick leave did not change this trend . Conclusions Caudal epidural steroid or saline injections are not recommended for chronic lumbar radiculopathy . Trial registration Current Controlled Trials IS RCT N No 12574253 Objectives The purpose of this study is to compare the effectiveness of interlaminar ( IL ) and bilateral transforaminal ( TF ) epidural steroid injections ( ESIs ) for pain reduction in patients with axial back pain result ing from herniated intervertebral disc ( HIVD ) and spinal stenosis ( SS ) . Methods Patients reporting axial back pain without radiation continuing over 3 months , which result ed from lumbosacral SS or HIVD were recruited and assigned to either the IL or TF technique group . The degree of pain and patient satisfaction were evaluated by the Numerical Rating Scale ( NRS ) , the Patient Satisfaction Index ( PSI ) , and the Rol and 5-point pain score , which were administered at pretreatment , 2 weeks , 2 months , and 4 months after ESI . Results Both the TF and IL ESIs accomplished significant pain reduction in HIVD and SS from 2 weeks to 4 months after treatment . SS showed a more significant reduction in the Rol and 5-point pain score and obtained more successful NRS results using the TF technique as compared with the IL technique . HIVD did not show any differences between the techniques . Discussion Bilateral TF epidural injection allowed the higher concentration of injectates to be delivered into ventral epidural space bilaterally . The IL approach can be more affected by tissue fibrosis , scarring , or hypertrophy , which is more prominently featured in SS than in HIVD ; these prevent the injectate delivered via the posterior route from spreading to the ventral epidural space . Consequently , in patients with SS , bilateral TF produces better results than IL Background and Objectives Systematic review s evaluate the utility of procedural interventions of the spine , including epidural steroid injections ( ESIs ) . However , existing quality assessment tools either fail to account for proper technical quality and patient selection or are not vali date d. We developed and vali date d a simple scale for ESIs to provide a quality assessment and rating of technique for injections of the spine ( AQUARIUS ) . Methods Seven experts generated items iteratively based on prior ESI technique studies and professional judgment . Following testing for face and content validity , a 17-item instrument was used by 8 raters from 2 different background s to assess 12 r and omized controlled trials , selected from 3 different categories . Using frequency of assessment , a 12-item instrument was also generated . Both instruments underwent reliability ( intraclass correlation coefficient ) , validity ( ability to distinguish “ low , ” “ r and om , ” and “ high ” study categories ) , and diagnostic accuracy ( receiver operating characteristics ) testing . Results Both 17- and 12-item instruments were scored consistently by raters regardless of background , with overall intraclass correlation coefficients of 0.72 ( 95 % confidence interval [ CI ] , 0.53–0.89 ) and 0.71 ( 95 % CI , 0.51–0.89 ) , respectively . Both instruments discriminated between clinical trials from all 3 categories . Diagnostic accuracy was similar for the 2 instruments , with areas under receiver operating characteristic curves of 0.89 ( 95 % CI , 0.82–0.96 ) and 0.90 ( 95 % CI , 0.82–0.97 ) , respectively . Conclusions The instrument in both 17- and 12-item formats demonstrates good reliability and diagnostic accuracy in rating ESI studies . As a complement to other tools that assess bias , the instrument may improve the ability to evaluate evidence for systematic review s and improve clinical trial design Background : This study was conducted to investigate the feasibility of using ultrasound as an image tool to locate the sacral hiatus accurately for caudal epidural injections . Methods : Between August 2002 and July 2003 , 70 patients ( 39 male and 31 female patients ) with low back pain and sciatica were studied . Soft tissue ultrasonography was performed to locate the sacral hiatus . A 21-gauge caudal epidural needle was inserted and guided by ultrasound to the sacral hiatus and into the caudal epidural space . Proper needle placement was confirmed by fluoroscopy . Results : In all the recruited patients , the sacral hiatus was located accurately by ultrasound , and the caudal epidural needle was guided successfully to the sacral hiatus and into the caudal epidural space . There was 100 % accuracy in caudal epidural needle placement into the caudal epidural space under ultrasound guidance as confirmed by contrast dye fluoroscopy . Conclusions : Ultrasound is radiation free , is easy to use , and can provide real-time images in guiding the caudal epidural needle into the caudal epidural space . Ultrasound may therefore be used as an adjuvant tool in caudal needle placement The objective of this study is to evaluate the efficacy of corticosteroids in patients with radicular pain due to lumbar disc herniation or lumbar spinal stenosis through a prospect i ve r and omised , double blind controlled trial , and whether there was an effect on subsequent interventions such as additional root blocks or surgery . Peri-radicular infiltration of corticosteroids has previously been shown to offer no additional benefit in patients with sciatica compared to local anaesthetic alone . It is not known if the response to peri-radicular infiltration is less marked in certain subgroups of patients such as those with radicular pain due to lumbar spinal stenosis . Previous studies have suggested that peri-radicular infiltration of corticosteroids may obviate the need for subsequent interventions and we therefore further investigated this in the current study . We r and omised 150 patients to receive a single injection with either bupivacaine alone or bupivacaine and methylprednisolone . Patients were assessed at 6 weeks and 3 months after the injection using st and ard outcome measures including Oswestry Disability Index ( ODI ) , visual analogue score for leg pain and patient ’s subjective assessment of outcome . At 1-year follow-up , we looked at the outcome in terms of the need for subsequent interventions such as additional root blocks or surgery . At 3-month follow-up , there was no statistically significant difference in the st and ard outcome measures between the two injection groups . At a minimum 1-year post injection , there was no difference in the need for subsequent interventions in either group . Patients with lumbar spinal stenosis had a less marked reduction in the ODI at 3 months with a mean change of 3.3 points when compared with 15 points for patients with lumbar disc herniation . In conclusion , peri-radicular infiltration of corticosteroids for sciatica does not provide any additional benefit when compared to local anaesthetic injection alone . Corticosteroids do not obviate the need for subsequent interventions such as additional root blocks or surgery OBJECTIVES To investigate the clinical effectiveness of epidural steroid injections ( ESIs ) in the treatment of sciatica with an adequately powered study and to identify potential predictors of response to ESIs . Also , to investigate the safety and cost-effectiveness of lumbar ESIs in patients with sciatica . DESIGN A pragmatic , prospect i ve , multicentre , double-blind , r and omised , placebo-controlled trial with 12-month follow-up was performed . Patients were stratified according to acute ( < 4 months since onset ) versus chronic ( 4 - 18 months ) presentation . All analyses were performed on an intention-to-treat basis with last observation carried forward used to impute missing data . SETTING Rheumatology , orthopaedic and pain clinics in four participating centres : three district hospitals and one teaching hospital in the south of Engl and . PARTICIPANTS Total of 228 patients listed for ESI with clinical ly diagnosed unilateral sciatica , aged between 18 and 70 years , who had a duration of symptoms between 4 weeks and 18 months . INTERVENTIONS Patients received up to three injections of epidural steroid and local anaesthetic ( active ) , or an injection of normal saline into the interspinous ligament ( placebo ) . MAIN OUTCOME MEASURES The primary outcome measure was the Oswestry Disability Question naire ( ODQ ) ; measures of pain relief and psychological and physical function were collected . Health economic data on return to work , analgesia use and other interventions were also measured . Quality -adjusted life-years ( QALYs ) were calculated using the SF-6D , calculated from the Short Form ( SF-36 ) . Costs per patient were derived from figures supplied by the centres ' finance departments and a costings exercise performed as part of the study . A cost-utility analysis was performed using the SF-36 to calculate costs per QALY . RESULTS ESI led to a transient benefit in ODQ and pain relief , compared with placebo at 3 weeks ( p = 0.017 , number needed to treat = 11.4 ) . There was no benefit over placebo between weeks 6 and 52 . Using incremental QALYs , this equates to and additional 2.2 days of full health . Acute sciatica seemed to respond no differently to chronic sciatica . There were no significant differences in any other indices , including objective tests of function , return to work or need for surgery at any time-points . There were no clinical predictors of response , although the trial lacked sufficient power to be confident of this . Adverse events were uncommon , with no difference between groups . Costs per QALY to providers under the trial protocol were 44,701 pounds sterling . Costs to the purchaser per QALY were 354,171 pounds sterling . If only one ESI was provided then costs per QALY fell to 25,745 pounds sterling to the provider and 167,145 pounds sterling to the purchaser . ESIs thus failed the QALY threshold recommended by the National Institute for Health and Clinical Excellence ( NICE ) . CONCLUSIONS Although ESIs appear relatively safe , it was found that they confer only transient benefit in symptoms and self-reported function in a small group of patients with sciatica at substantial costs . ESIs do not provide good value for money if NICE recommendations are followed . Additional research is suggested into the epidemiology of radicular pain , producing a register of all ESIs , possible subgroups who may benefit from ESIs , the use of radiological imaging , optimal early interventions , analgesic agents and nerve root injections , the use of cognitive behavioural therapy in rehabilitation , improved methods of assessment , a comparative cost-utility analysis between various treatment strategies , and methods to reduce the effect of scarring and inflammation BACKGROUND The pathophysiology of lumbar radicular pain is a subject of ongoing research . The prevalence of sciatica or radiculitis ranges from 1.2 % to 43 % . Epidural injections are one of the most commonly performed interventions in the United States in managing chronic low back and lower extremity pain secondary to disc herniation and radiculitis . There is a paucity of evidence with contemporary methodology used in performing epidural injections under fluoroscopy and based on pain relief and functional status improvement . STUDY DESIGN A r and omized , double-blind , equivalence trial . SETTING An interventional pain management practice , a specialty referral center , a private practice setting in the United States . OBJECTIVE To evaluate the effectiveness of caudal epidural injections with or without steroids in managing chronic low back and lower extremity pain secondary to disc herniation or radiculitis in providing effective and long-lasting pain relief and evaluate the differences between local anesthetic with or without steroids . METHODS Patients were assigned to one of 2 groups ; Group I patients received caudal epidural injections with an injection of local anesthetic ( lidocaine 0.5 % ) , whereas , Group II patients received caudal epidural injections with 0.5 % lidocaine 9 mL mixed with 1 mL of steroid . R and omization was performed by computer-generated r and om allocations sequence by simple r and omization . OUTCOMES ASSESSMENT Multiple outcome measures were utilized which included the Numeric Rating Scale ( NRS ) , the Oswestry Disability Index 2.0 ( ODI ) , employment status , and opioid intake with assessment at 3 months , 6 months , and 12 months post-treatment . Significant pain relief was defined as 50 % or more , whereas significant improvement in disability score was defined as a reduction of 40 % or more . RESULTS The percentage of patients with significant pain relief of 50 % or greater at 12 months was 79 % in Group I and 81 % in Group II . Reduction of Oswestry scores of at least 40 % was seen in 83 % of the patients in Group I and 91 % in Group II . The overall average procedures per year were 3.9 + /- 1.26 in Group I and 3.6 + /- 1.08 in Group II with an average total relief per year of 35.2 + /- 17.18 weeks in Group I and 35.9 + /- 15.34 weeks in Group II over a period of 52 weeks . LIMITATIONS The results of this study are limited by lack of a placebo group and a preliminary report of 42 patients in each group . CONCLUSION Caudal epidural injections with or without steroids may be effective in patients with disc herniation or radiculitis with between 79 % to 91 % of patients showing significant pain relief and improvement in functional status Study Design . Multicenter , r and omized , double-blind , placebo-controlled trial . Objective . To examine the safety and efficacy of three different doses of the tumor necrosis factor alpha ( TNF-&agr ; ) inhibitor etanercept versus placebo for the treatment of symptomatic lumbar disc herniation ( LDH ) . Summary of Background Data . TNF-&agr ; is considered to be a major cause of radicular leg pain associated with symptomatic LDH . Systemic administration of TNF-&agr ; inhibitors for sciatica has indicated a trend toward efficacy . Methods . Forty-nine subjects aged between 18 and 70 years , with persistent lumbosacral radicular pain secondary to LDH , and an average leg pain intensity of 5/10 or more were r and omized to 1 of 4 groups : 0.5-mg , 2.5-mg , 12.5-mg etanercept , or placebo . Subjects received 2 transforaminal epidural injections , 2 weeks apart , and were assessed for efficacy up to 26 weeks after the second injection . The primary outcome measure was the change in mean daily worst leg pain ( WLP ) . Secondary outcomes included average leg pain , worst back pain , average back pain , in-clinic pain , Oswestry Disability Index , patient global impression of change , and tolerability . Results : Forty-three of the 49 r and omized patients completed the study . Patients receiving 0.5-mg etanercept showed a clinical ly and statistically significant ( P < 0.1 ) reduction in mean daily WLP compared with the placebo cohort from 2 to 26 weeks for both the per protocol population ( −5.13 vs. −1.95 ; P= 0.066 ) and the intention-to-treat population ( −4.40 vs. −1.84 ; P= 0.058 ) . Fifty percent of these subjects reported a 100 % reduction in WLP 4 weeks post-treatment compared with 0 % of subjects in the placebo cohort . Improvements in all secondary outcomes were also observed in the 0.5-mg etanercept cohort . The overall incidence of adverse events was similar in placebo and all etanercept cohorts . Conclusion . Two transforaminal injections of etanercept provided clinical ly significant reductions in mean daily WLP and worst back pain compared with placebo for subjects with symptomatic LDH . Epidural etanercept may offer patients with sciatica a safe and effective nonoperative treatment . Level of Evidence : A r and omized trial of lumbar epidural injections for the treatment of acute sciatic pain was carried out . All the patients had unilateral sciatica for less than six months and had never previously been treated in hospital for their backs . The treatments used were 20 ml normal saline , 80 mg Depomedrone in normal saline made up to 20 ml , 20 ml , 20 ml 0.25 % bupivacaine solution and needling with a st and ard Touhy injection needle into the interspinous ligament but with no injection . The patients improved at about the same rate for all four treatments . Overall , 75 % of the patients improved or were cured . As some of these were in the group treated by needling of the interspinous ligament , it seems likely that the epidural injections administered achieved effects partially as a placebo and partially by virtue of the natural history of the acute sciatic syndrome OBJECTIVE Sciatica is thought to have a good clinical outcome , but in fact , its natural history is not well known . STUDY DESIGN AND SETTING We studied a prospect i ve cohort of 3,164 workers from the French national electricity and gas company . In this cohort , 622 subjects suffered from sciatica in 1991 . The predictive factors of the persistence or recurrence of sciatica after 2 years were identified by multivariate analysis ( logistic regression ) . RESULTS Of the 622 subjects with sciatica in 1991 , 55 % still reported its symptoms in 1993 and 53 % in 1995 . Of those who had recovered from sciatica in 1993 , 61 % still had low back pain and 27 % of them long-lasting low back pain in 1993 . The factors predictive of the persistence or recurrence of sciatica in 1993 , identified by multivariate analysis , were : driving at least 2 hr/day , carrying heavy loads at work , a high level of psychosomatic problems , and sciatica symptoms the year before study inclusion . CONCLUSION Recovery from sciatica is less frequent than expected . Attention should be given to occupational and personal factors associated with persistence or recurrence of sciatica In this prospect i ve r and omized clinical trial , the results of epidural corticosteroid injections were evaluated in patients with lumbosciatic pain caused by herniated nucleus pulposus . Thirty-six patients with radicular lumbosciatic pain and positive straight leg raising test because of confirmed prolapsed intervertebral lumbar discs were r and omized into two groups with ( 17 patients ) and without ( 19 patients ) epidural corticosteroid injection . Members of the treatment groups received three injections of 100 mg methylprednisolone in 10 mL bupivacaine 0.25 % each . Additional therapy was st and ardized and identical in both groups . Followup examinations were performed at 2 weeks , 6 weeks , and 6 months . The examinations included pain level ( visual analogue scale ) , straight leg raising test , and functional status ( Hannover Functional Ability Question naire ) . At 2 weeks , patients receiving methylprednisolone injection showed a significant improvement in straight leg raising test results compared with patients in the control group . Results were better in the methylprednisolone group , although not statistically significant for pain relief and mobility . At 6 weeks and 6 months , pain relief , improvement of straight leg raising , and improvement of functional status showed no statistical significance . Epidural corticosteroid injections can be recommended as additional therapy only in the acute phase of the conservative management of lumbosciatic pain Study Design . A prospect i ve study r and omized by patient choice from the private practice of a single physician affiliated with a major teaching hospital was conducted . Objectives . To compare transforaminal epidural steroid injections with saline trigger-point injections used in the treatment of lumbosacral radiculopathy secondary to a herniated nucleus pulposus . Summary of Background Data . Epidural steroid injections have been used for more than half a century in the management of lumbosacral radicular pain . At this writing , however , there have been no controlled prospect i ve trials of transforaminal epidural steroid injections in the treatment of lumbar radiculopathy secondary to a herniated nucleus pulposus . Methods . R and omized by patient choice , patients received either a transforaminal epidural steroid injection or a saline trigger-point injection . Treatment outcome was measured using a patient satisfaction scale with choice options of 0 ( poor ) , 1 ( fair ) , 2 ( good ) , 3 ( very good ) , and 4 ( excellent ) ; a Rol and -Morris low back pain question naire that showed improvement by an increase in score ; a measurement of finger-to-floor distance with the patient in fully tolerated hip flexion ; and a visual numeric pain scale ranging from 0 to 10 . A successful outcome required a patient satisfaction score of 2 ( good ) or 3 ( very good ) , improvement on the Rol and -Morris score of 5 or more , and pain reduction greater than 50 % at least 1 year after treatment . The final analysis included 48 patients with an average follow-up period of 16 months ( range , 12–21 months ) . Results . After an average follow-up period of 1.4 years , the group receiving transforaminal epidural steroid injections had a success rate of 84 % , as compared with 48 % for the group receiving trigger-point injections ( P < 0.005 ) . Conclusion . Fluoroscopically guided transforaminal injections serve as an important tool in the nonsurgical management of lumbosacral radiculopathy secondary to a herniated nucleus pulposus The use of extradural injections to relieve backache has been the subject of a number of studies in recent years . The idea is not a new one ; as long ago as 1901 Sicardl employed extradural cocaine by the caudal route to treat three cases of lumbago and four of sciatica-'recovery was maintained for 14 days ' . In 1925 Vinerz published a small series of cases in whom sciatica was treated by caudal extradural injection of 2Oml 1 % procaine followed by 50 - 1oOml Ringers solution , normal saline or liquid petrolatum . In 1930 Evans3 reported on the use of sacral extradural injection of 60 - 8Oml normal saline or procaine in 40 patients ; he cl aim ed that the condition was improved in 14 % . Many further reports of encouraging results following the administration of extradural saline and /or local analgesic have been published,4 - 8 . The use of steroid preparations by the extradural route was first employed in 1953 by Lievreg and in 1961 Goebert et al. 10 reported a series of 113 patients with painful radiculopathy treated with epidural procaine and hydrocortisone acetate . Since then a number of similar series have been published which c o n m the value of the method 11 - 14 . The present study was carried out in the SaIford Group of Hospitals over the ten year period ( mid-I958 to mid-1968 ) . Of a total of over 5,000 patients complaining of backache 530 considered to be suffering from the lumbosciatic syndrome were treated by extradural injection of either normal saline , local analgesic or methyl-prednisolone acetate ( Depomedrone ) . In the earlier years of the study the former two agents only were employed . They were given either by the lumbar or the caudal route and in r and om order . Since 1963 we have used methylprednisolone exclusively , and this has always been injected into the lumbar extradural space . All the 325 patients included in this report have been followed up for at least 12 months BACKGROUND Spinal stenosis is one of the 3 most common diagnoses of low back and leg symptoms which also include disc herniation and degenerative spondylolisthesis . Spinal stenosis is a narrowing of the spinal canal with encroachment on the neural structures by surrounding the bone and soft tissue . In the United States , one of the most commonly performed interventions for managing chronic low back pain are epidural injections , including their use for spinal stenosis . However , there have not been any r and omized trials and evidence is limited with regards to the effectiveness of epidural injections in managing chronic function-limiting low back and lower extremity pain secondary to lumbar spinal stenosis . STUDY DESIGN A r and omized , double-blind , equivalence trial . SETTING An interventional pain management practice , a specialty referral center , a private practice setting in the United States . OBJECTIVES To evaluate the effectiveness of caudal epidural injections with or without steroids in providing effective and long-lasting pain relief in the management of chronic low back pain in spinal stenosis and to evaluate the differences between local anesthetic with or without steroids . METHODS Patients were r and omly assigned to one of 2 groups , with Group I patients receiving caudal epidural injections of local anesthetic ( lidocaine 0.5 % ) , whereas Group II patients received caudal epidural injections with 0.5 % lidocaine 9 mL mixed with 1 mL of steroid . R and omization is being performed by computer-generated r and om allocation sequence by simple r and omization . OUTCOMES ASSESSMENT Multiple outcome measures were utilized which included the Numeric Rating Scale ( NRS ) , the Oswestry Disability Index 2.0 ( ODI ) , employment status , and opioid intake with assessment at 3 months , 6 months , and 12 months post-treatment . Significant pain relief was defined as 50 % or more , whereas significant improvement in disability score was defined as reduction of 40 % or more . RESULTS Significant pain relief ( > or = 50 % ) was demonstrated in 55 % to 65 % of the patients and functional status improvement with 40 % reduction in ODI scores in 55 % to 80 % of the patients . The overall average procedures per year were 3.4 + /- 1.27 in Group I and 2.6 + /- 1.35 in Group II with an average total relief per year of 30.3 + /- 19.49 weeks in Group I and 23.1 + /- 21.36 weeks in Group II over a period of 52 weeks . LIMITATIONS The results of this study are limited by the lack of a placebo group and a preliminary report of 20 patients in each group , even though sample was justified . CONCLUSION Caudal epidural injections with or without steroids may be effective in patients with chronic function-limiting low back and lower extremity pain with spinal stenosis in approximately 60 % of the patients A double blind study was carried out in 51 patients suffering from lumbar root compression syndrome of 12 days to 36 weeks duration . All patients had signs , symptoms and radiological abnormalities related to a herniated lumbar disc . Each patient received an extradural injection of either 2 ml ( 80 mg ) methyl prednisolone or 2 ml normal saline solution . Neurological examination and interview of the patients with the aid of a question naire before and after extradural injection failed to demonstrate any statistically significant difference in outcome between the two groups . At follow-up 14 + /- 6 months after extradural injection 58.3 per cent of the patients in the control group and 51.9 per cent of the patients in the treatment group had undergone surgical treatment with laminectomy . Our results indicate that a single extradural injection of methyl prednisolone ( 80 mg ) is no more effective than a placebo injection in relieving chronic symptoms due to myelographically demonstrable lumbar disc herniation BACKGROUND Lumbar disc herniation and radiculitis are common elements of low back and lower extremity pain . Among minimally invasive treatments , epidural injections are one of the most commonly performed interventions . However , the literature is mixed about their effectiveness in managing low back and lower extremity pain . In general , individual studies and systematic review s of epidural steroid injections have been hampered by their study design , baseline differences between treatment groups , inadequate sample sizes , highly controlled setting s , lack of vali date d outcome measures , and the inability to confirm the injectate location because fluoroscopy was not used . STUDY DESIGN A r and omized , controlled , double blind , active control trial . SETTING A private , interventional pain management practice , specialty referral center in the United States . OBJECTIVES To assess the effectiveness of fluoroscopically directed caudal epidural injections with local anesthetic with or without steroids in managing chronic low back and lower extremity pain in patients with disc herniation and radiculitis . METHODS One hundred twenty patients were r and omized to two groups : Group I received 10 mL caudal epidural injections of local anesthetic , lidocaine 0.5 % ; Group II patients received caudal epidural injections of 0.5 % lidocaine , 9 mL , mixed with 1 mL of steroid . OUTCOME ASSESSMENT Multiple outcome measures were utilized . The primary outcome measures were Numeric Rating Scale ( NRS ) and the Oswestry Disability Index 2.0 ( ODI ) . Secondary outcome measures were employment status and opioid intake . Significant pain relief improvement was defined as 50 % or more improvement in NRS and ODI scores . RESULTS In the successful category , 77 % of Group I had significant pain relief of > /= 50 % and functional status improvement of > /= 50 % reduction in ODI scores ; in Group II it was 76 % , whereas overall it was 60 % and 65 % in Groups I and II . Over the two years , Group I had an average number of procedures of 5.5 ± 2.8 ; Group II was 5.3 ± 2.4 . Even though there was no significant difference in overall relief between the two groups , the average relief for each procedure was superior for steroids . LIMITATIONS Presumed limitations of this evaluation include lack of a placebo group . CONCLUSION Caudal epidural injections of local anesthetic with or without steroids might be an effective therapy for patients with disc herniation or radiculitis . The present evidence illustrates the potential superiority of steroids compared with local anesthetic at two year follow up based on average relief per procedure . TRIAL REGISTRATION NCT00370799 We have assessed whether an epidural steroid injection is effective in the treatment of symptoms due to compression of a nerve root in the lumbar spine by carrying out a prospect i ve , r and omised , controlled trial in which patients received either an epidural steroid injection or an intramuscular injection of local anaesthetic and steroid . We assessed a total of 93 patients according to the Oxford pain chart and the Oswestry disability index and followed up for a minimum of two years . All the patients had been categorised as potential c and i date s for surgery . There was a significant reduction in pain early on in those having an epidural steroid injection but no difference in the long term between the two groups . The rate of subsequent operation in the groups was similar OBJECTIVES To determine the therapeutic value and long-term effects of fluoroscopic transforaminal epidural steroid injections in patients with refractory radicular leg pain . BACKGROUND DATA Although numerous studies have evaluated the efficacy of traditional transsacral ( caudal ) or translaminar ( lumbar ) administration of epidural steroids , to our knowledge no studies have assessed specifically the therapeutic value of fluoroscopic transforaminal epidural steroids . STUDY DESIGN A prospect i ve case series that investigated the outcome of patients with lumbar herniated nucleus pulposus and radiculopathy who received fluoroscopic transforaminal epidural steroid injections . METHODS Patients who met our inclusion criteria received fluoroscopically guided , contrast-enhanced transforaminal epidural administration of anesthetic and steroid directly at the level and side of their documented pathology . Patients were evaluated by an independent observer and received sequential question naires before and after injection , documenting pain level , activity level , and patient satisfaction . RESULTS Sixty-nine patients met our inclusion criteria and were followed for an average period of 80 weeks ( range , 28 to 144 weeks ) ; 75.4 % of patients had a successful long-term outcome , reporting at least a > 50 % reduction between preinjection and postinjection pain scores , as well as an ability to return to or near their previous levels of functioning after only 1.8 injections per patient ( range , 1 to 4 injections ) . Of our patients , 78.3 % were satisfied with their final outcomes . CONCLUSIONS Fluoroscopic transforminal epidural steroids are an effective nonsurgical treatment option for patients with lumbar herniated nucleus pulposus and radiculopathy in whom more conservative treatments are not effective and should be considered before surgical intervention Study Design . R and omized , double-blinded clinical trial . Objective . To compare effi cacies of two active therapies for chronic low back pain . Summary of Background Data . Radicular pain may result from intervertebral disc herniation . Clonidine has demonstrated analgesic and anti-infl ammatory activity in animal studies on nerve injury . Extensive clinical experience supports neuraxial clonidine ’s safety . Methods . Patients with approximately 3 months of low back pain and leg pain due to intervertebral disc herniation were r and omized to transforaminal epidural injection(s ) of 2 % lidocaine and either clonidine ( 200 or 400 g ) or triamcinolone ( 40 mg ) . Patients received one to three injections administered at about 2 weeks apart . Patients , investigators , and study coordinators were blinded to the treatment . The primary outcome was an 11-point Pain Intensity Numerical Rating Scale at 1 month . Other outcomes included Patient Global Impression of Change and functional measures . Results . Of the 33 patients screened and r and omized , 26 enrolled , of which 11 received clonidine and 15 triamcinolone . Both groups showed signifi ca nt improvement in pain score at 2 weeks and 1 month compared with baseline ( P 0.05 ) . The corticosteroid group showed additional functional improvement at 1 month with respect to clonidine ( P 0.022 ) . There was no difference between groups for primary outcome . However , as target enrollment was not reached , we can not say with confi dence that the two treatments would be expected to result in similar short-term pain relief . Adverse effects were common in both groups , but there were no serious complications . Conclusions . Radicular pain due to intervertebral disc herniation improved rapidly with transforaminal epidural injection of either clonidine or triamcinolone . Corticosteroid result ed in greater functional improvement , with unclear differences in analgesia . INTRODUCTION : Lumbar epidural steroid injection can be accomplished by one of three methods : caudal ( C ) , interlaminar ( IL ) , or transforaminal ( TF ) . In this study we sought to determine the efficacy of these techniques for the management of radicular pain associated with lumbar disk herniations . METHODS : Ninety patients aged 18–60 years with L5-S1 disk herniations and radicular pain were r and omly assigned to one of these groups to have epidural steroid injection therapy every 2 wk for a maximum of three injections . Pain relief , disability , and activity levels were assessed . RESULTS : Pain relief was significantly more effective with TF injections . At 24 wk from the initiation of this study , pain relief was as follows : C : complete pain relief : 1/30 , partial pain relief : 16/30 , and no relief : 13/30 ; IL : complete pain relief : 3/30 , partial pain relief : 15/30 , and no relief : 12/30 ; and TF : complete pain relief : 9/30 , partial pain relief : 16/30 , and no relief : 5/30 . CONCLUSIONS : The TF route of epidural steroid placement is more effective than the C or IL routes . We attribute this observation to a higher incidence of steroid placement in the ventral epidural space when the TF method is used BACKGROUND Lumbar disk herniation ( LDH ) is considered a common cause of lumbosacral radiculopathy . Epidural steroid injection is a common method to treat inflammation associated with low back-related leg pain . Spinal manipulations are widely used , and systematic review s have also shown that these manipulations are more effective than placebos . OBJECTIVE Due to the absence of clinical evidence , we design ed a prospect i ve , r and omized , single-blind controlled trial in patients with LDH with radiculopathy , aim ing to detect the safety and clinical efficacy of targeted indwelling catheter combined with " 4-step " manipulative therapy in patients with LDH . METHODS Patient visits were performed at baseline and days 1 , 3 , 7 , and 28 after treatment . Clinical outcomes were measured using visual analog scale for back and leg pain , Oswestry Disability Index ( ODI ) , and clinical symptom scores of the Japanese Orthopedic Association ( JAO ) . RESULTS The study included 85 eligible patients . They were categorized with a r and omization schedule into a Catheter Group ( N = 43 ) and No-Catheter Group ( N = 42 ) . Between the measurement points , there was a statistically significant difference in the visual analog scale ( back ) at days 1 , 3 , and 7 of follow-up after treatment between the 2 groups . The change was statistically different at days 1 and 3 , and a higher change was observed in the Catheter Group compared with the No-Catheter Group . There was a statistically significant difference in change of JOA and ODI scores at day 1 of follow-up after treatment between the 2 groups , and a greater change was seen in the Catheter Group at days 1 and 3 compared with the No-Catheter Group . LIMITATIONS The small sample size was small , and the follow-up time was short . The study also lacked documents of adjuvant therapies , like individual patient exercise routines and analgesic drug therapy . CONCLUSION Both methods were effective in reducing pain intensity and functional disability compared with pretreatment . The Catheter Group showed a more significant decrease in visual analog scale and greater changes in JOA and ODI scores of short/term follow-up , compared with the No-Catheter Group . The therapy project was safe Objectives The aim of the study was to evaluate the influence of the depth of local anesthesia application on procedural pain during lumbar transforaminal epidural steroid injection . Design Sixty-eight patients were enrolled who were scheduled for single-level , unilateral fluoroscopically guided lumbar transforaminal epidural steroid injection . Patients were r and omly allocated to receive either subcutaneous local anesthesia ( group S ) or deep local anesthesia ( group D ) for transforaminal epidural steroid injection . The data related to pain and technical performance during the procedure was compared . In addition , the incidence of injection site soreness was assessed 2 wks after transforaminal epidural steroid injection . Results Sixty-seven patients completed all assessment s ( group S , n = 33 ; group D , n = 34 ) . There was no significant difference in procedural pain and discomfort level between the groups ( P = 0.151 , P = 0.183 , respectively ) . Patients in group D showed lower behavioral pain scores ( P = 0.017 ) . There was no significant difference in the numbers of needle manipulations , fluoroscopy time , and radiation dose during the procedure between the groups . Two patients in group S and three in group D complained of injection site soreness after transforaminal epidural steroid injection for a few days , but there was no significant difference in its incidence ( P = 0.667 ) . Conclusions Deep local anesthesia to reduce procedural pain during transforaminal epidural steroid injection seems to have no significant clinical benefit compared with conventional subcutaneous local anesthesia . To Cl aim CME Credits Complete the self- assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME Objectives Reduce procedural pain by considering clinical factors of the patient during fluoroscopically guided lumbar transforaminal epidural injections . Upon completion of this article , the reader should be able to : ( 1 ) Underst and the potential impact of procedural pain on the performance of transforaminal epidural steroid injections ; ( 2 ) Distinguish cutaneous nociceptive afferents from nociceptive afferents in muscle ; and ( 3 ) Explain the factors to reduce procedural pain during fluoroscopically guided lumbar transforaminal epidural injections . Level Advanced Accreditation The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians . The Association of Academic Physiatrists design ates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™ . Physicians should only cl aim credit commensurate with the extent of their participation in the activity Study Design . Prospect i ve , double-blind , r and omized , case-control study . Objective . To evaluate the efficacy of caudal epidural injections ( CEI ) containing steroid versus nonsteroid preparations when treating patients suffering from low back pain ( LBP ) and sciatica . Summary of Background Data . Literature seems to be deprived of well- design ed r and omized , controlled studies that evaluate the effectiveness of CEI in the treatment of chronic LBP ; hence the value of CEI remains still the subject of controversy . Methods . Patients suffering from severe chronic LBP and sciatica were r and omly allocated into 2 groups . Steroid-group ’s patients ( n = 93 ) underwent CEI containing 12 mL of xylocaine 2 % and 1 mL of betamethasone dipropionate and betamethasone phosphate ( 2 + 5 ) mg/dL. Water for Injection (WFI)-group ’s patients ( n = 90 ) underwent CEI containing 12 mL of xylocaine 2 % and 8 mL of WFI . Both groups were statistically comparable as far as their demographic data and the cause and duration of symptoms were concerned . Patients answered the Oswestry Disability Index question naire and underwent physical examination , before and at 1 week , 1 month , 6 months , and 1 year following the CEI . Results . Symptoms improved in 132 patients ( 72.1 % ) following CEI . The mean Oswestry Disability Index question naire score of steroid-group ’s patients was statistically significant lower than that of the WFI-group at all postinjection re-evaluations . Patients receiving steroid CEI experienced faster relief during the first postinjection week . The Straight Leg Rising test improved in both groups following CEI ; this improvement was faster among steroid-group ’s patients . Fifty-one patients ( 27.8 % ) , noticed no improvement 1 week post-CEI and underwent a second CEI ( with the same preparation ) 7 to 14 days later . Nineteen of them reported improvement ; 32 ( steroid-group:13 , WFI-group:19 ) did not respond well and underwent operative decompression ( n = 15 ) or spinal fusion ( n = 17 ) . Conclusion . CEI containing local anesthetic and steroids or WFI seems to be effective when treating patients with LBP and sciatica . CEI containing steroid preparations demonstrated better and faster efficacy OBJECTIVE To describe and answer questions concerning the spread of contrast in patients receiving correctly placed lumbar epidural steroid injections ( ESIs ) under fluoroscopy . DESIGN Prospect i ve observational study . SETTING An outpatient surgery center . PARTICIPANTS Consecutive patients ( N=114 ) receiving ESIs under fluoroscopy who met inclusion criteria . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Spread of contrast in relation to variables , including unilateral versus bilateral , anterior versus posterior , and spread more than 1 level caudally versus less than 1 level . Variables were examined in relation to needle tip placement , level of injection , and male versus female patients . All data were collected with fluoroscopy images in lateral and anteroposterior views after injection of 5 mL of fluid . RESULTS Spread was greater than 1 segment caudally more than 75 % of the time under all variables . Anterior versus posterior epidural spread on the lateral view was approximately even over all cases and anterior spread was found more often when the needle was within the width of the distal spinous process tip . Needle placement medial or lateral to the spinous process width also significantly affected whether the spread was unilateral versus bilateral . If the needle tip was lateral to the width of the spinous process , spread was unilateral 75 % of the time , versus 45 % of the time if the needle tip was medial . CONCLUSIONS Contrast spread is affected by needle placement , with other variables kept equal , in the performance of an interlaminar lumbar ESI . These data support the performance of interlaminar lumbar ESIs with fluoroscopic guidance and provide some parameters with which to guide the injectionist BACKGROUND Transforaminal injection of steroids is used to treat lumbar radicular pain . Not known is whether the route of injection or the agent injected is significant . STUDY DESIGN A prospect i ve , r and omized study compared the outcomes of transforaminal injection of steroid and local anesthetic , local anesthetic alone , or normal saline , and intramuscular injection of steroid or normal saline . Patients and outcome evaluators were blinded as to agent administered . METHODS The primary outcome measure was the proportion of patients who achieved complete relief of pain , or at least 50 % relief , at 1 month after treatment . Secondary outcome measures were function , disability , patient-specified functional outcomes , use of other health care , and duration of relief beyond 1 month . RESULTS A significantly greater proportion of patients treated with transforaminal injection of steroid ( 54 % ) achieved relief of pain than did patients treated with transforaminal injection of local anesthetic ( 7 % ) or transforaminal injection of saline ( 19 % ) , intramuscular steroids ( 21 % ) , or intramuscular saline ( 13 % ) . Relief of pain was corroborated by significant improvements in function and disability , and reductions in use of other health care . Outcomes were equivalent for patients with acute or chronic radicular pain . Over time , the number of patients who maintained relief diminished . Only some maintained relief beyond 12 months . The proportions of patients doing so were not significantly different statistically between groups . DISCUSSION Transforaminal injection of steroids is effective only in a proportion of patients . Its superiority over other injections is obscured when group data are compared but emerges when categorical outcomes are calculated . Over time , the proportion of patients with maintained responses diminishes |
1,691 | 18,241,758 | Meta- analysis of trials to date shows CAS is associated with higher 30-day risk of stroke/death compared with CEA .
Thus , for the patient at average surgical risk , the role of CAS is unproven , especially for symptomatic patients .
And for the patient at high surgical risk , the role of any intervention is uncertain in the setting of competing comorbidities . | OBJECTIVES Carotid artery stenting ( CAS ) is an alternative to carotid endarterectomy ( CEA ) for treating carotid artery stenosis .
We conducted a systematic review and meta- analysis of the clinical trials to date comparing these two procedures to determine their relative safety and efficacy . | Since the 1950s carotid endarterectomy has been performed in patients with symptomatic carotid artery stenosis , based on suggestive but inconclusive evidence for its effectiveness . Only during the last 5 years have r and omized studies clarified the indications for surgery . In preparing this report , panel members used the same rules of evidence used in the previous report1 2 ( Table ⇓ ) . View this table : Table 1 . Levels of Evidence and Grading of Recommendations Few studies have analyzed control of risk factors in a r and omized , prospect i ve manner following carotid endarterectomy . However , a wealth of data are available regarding the general relationship between risk factor control and stroke risk . These data provide some guidance for the care of endarterectomy patients . # # # Hypertension Hypertension is the most powerful , prevalent , and treatable risk factor for stroke.3 Both systolic and diastolic blood pressure are independently related to stroke incidence . Isolated systolic hypertension , which is common in the elderly , also considerably increases risk of stroke . Reduction of elevated blood pressure significantly lowers risk of stroke . Meta-analyses of r and omized trials found that an average reduction in diastolic blood pressure of 6 mm Hg produces a 42 % reduction in stroke incidence.3 4 Treatment of isolated systolic hypertension in people older than 60 years also reduces stroke incidence by 36 % without an excessive number of side effects such as depression or dementia.5 Long-term care of patients after endarterectomy should include careful control of hypertension ( Grade A recommendation for treatment of hypertension in general ; Grade C recommendation for postendarterectomy care ) . Perioperative treatment of hypertension after carotid endarterectomy represents a special situation . Poor control of blood pressure after endarterectomy increases risk of cerebral hyperperfusion syndrome.6 7 8 9 This complication is characterized by unilateral headache , seizures , and occasionally altered mental status or focal neurological signs . Neuroimaging may show intracerebral hemorrhages10 11 12 or white OBJECTIVE To determine whether the addition of carotid endarterectomy to aggressive medical management can reduce the incidence of cerebral infa rct ion in patients with asymptomatic carotid artery stenosis . DESIGN Prospect i ve , r and omized , multicenter trial . SETTING Thirty-nine clinical sites across the United States and Canada . PATIENTS Between December 1987 and December 1993 , a total of 1662 patients with asymptomatic carotid artery stenosis of 60 % or greater reduction in diameter were r and omized ; follow-up data are available on 1659 . At baseline , recognized risk factors for stroke were similar between the two treatment groups . INTERVENTION Daily aspirin administration and medical risk factor management for all patients ; carotid endarterectomy for patients r and omized to receive surgery . MAIN OUTCOME MEASURES Initially , transient ischemic attack or cerebral infa rct ion occurring in the distribution of the study artery and any transient ischemic attack , stroke , or death occurring in the perioperative period . In March 1993 , the primary outcome measures were changed to cerebral infa rct ion occurring in the distribution of the study artery or any stroke or death occurring in the perioperative period . RESULTS After a median follow-up of 2.7 years , with 4657 patient-years of observation , the aggregate risk over 5 years for ipsilateral stroke and any perioperative stroke or death was estimated to be 5.1 % for surgical patients and 11.0 % for patients treated medically ( aggregate risk reduction of 53 % [ 95 % confidence interval , 22 % to 72 % ] ) . CONCLUSION Patients with asymptomatic carotid artery stenosis of 60 % or greater reduction in diameter and whose general health makes them good c and i date s for elective surgery will have a reduced 5-year risk of ipsilateral stroke if carotid endarterectomy performed with less than 3 % perioperative morbidity and mortality is added to aggressive management of modifiable risk factors BACKGROUND The efficacy of carotid endarterectomy in patients with asymptomatic carotid stenosis has not been confirmed in r and omized clinical trials , despite the widespread use of operative intervention in such patients . METHODS We conducted a multicenter clinical trial at 11 Veterans Affairs medical centers to determine the effect of carotid endarterectomy on the combined incidence of transient ischemic attack , transient monocular blindness , and stroke . We studied 444 men with asymptomatic carotid stenosis shown arteriographically to reduce the diameter of the arterial lumen by 50 percent or more . The patients were r and omly assigned to optimal medical treatment including antiplatelet medication ( aspirin ) plus carotid endarterectomy ( the surgical group ; 211 patients ) or optimal medical treatment alone ( the medical group ; 233 patients ) . All the patients at each center were followed independently by a vascular surgeon and a neurologist for a mean of 47.9 months . RESULTS The combined incidence of ipsilateral neurologic events was 8.0 percent in the surgical group and 20.6 percent in the medical group ( P < 0.001 ) , giving a relative risk ( for the surgical group vs. the medical group ) of 0.38 ( 95 percent confidence interval , 0.22 to 0.67 ) . The incidence of ipsilateral stroke alone was 4.7 percent in the surgical group and 9.4 percent in the medical group . An analysis of stroke and death combined within the first 30 postoperative days showed no significant differences . Nor were there significant differences between groups in an analysis of all strokes and deaths ( surgical , 41.2 percent ; medical , 44.2 percent ; relative risk , 0.92 ; 95 percent confidence interval , 0.69 to 1.22 ) . Overall mortality , including postoperative deaths , was primarily due to coronary atherosclerosis . CONCLUSIONS Carotid endarterectomy reduced the overall incidence of ipsilateral neurologic events in a selected group of male patients with asymptomatic carotid stenosis . We did not find a significant influence of carotid endarterectomy on the combined incidence of stroke and death , but because of the size of our sample , a modest effect could not be excluded BACKGROUND Percutaneous transluminal angioplasty and stenting ( endovascular treatment ) can be used to treat carotid stenosis , but risks and benefits are uncertain . We therefore compared endovascular treatment with conventional carotid surgery . METHODS In a multicentre clinical trial , we r and omly assigned 504 patients with carotid stenosis to endovascular treatment ( n=251 ) or carotid endarterectomy ( n=253 ) . For endovascular patients treated successfully , we used stents in 55 ( 26 % ) and balloon angioplasty alone in 158 ( 74 % ) . An independent neurologist followed up patients . Analysis was by intention to treat . FINDINGS The rates of major outcome events within 30 days of first treatment did not differ significantly between endovascular treatment and surgery ( 6.4 % vs 5.9 % , respectively , for disabling stroke or death ; 10.0 % vs 9.9 % for any stroke lasting more than 7 days , or death ) . Cranial neuropathy was reported in 22 ( 8.7 % ) surgery patients , but not after endovascular treatment ( p<0.0001 ) . Major groin or neck haematoma occurred less often after endovascular treatment than after surgery ( three [ 1.2 % ] vs 17 [ 6.7 % ] , p<0.0015 ) . At 1 year after treatment , severe ( 70 - 99 % ) ipsilateral carotid stenosis was more usual after endovascular treatment ( 25 [ 14 % ] vs seven [ 4 % ] , p<0.001 ) . However , no substantial difference in the rate of ipsilateral stroke was noted with survival analysis up to 3 years after r and omisation ( adjusted hazard ratio=1.04 , 95 % CI 0.63 - 1.70 , p=0.9 ) . INTERPRETATION Endovascular treatment had similar major risks and effectiveness at prevention of stroke during 3 years compared with carotid surgery , but with wide CIs . Endovascular treatment had the advantage of avoiding minor complications OBJECTIVE Current clinical trials evaluating carotid stenting have focused on high-risk patients and may not reflect the broad population of patients with carotid stenosis who undergo treatment to prevent stroke . The Carotid Revascularization Using Endarterectomy or Stenting Systems ( CaRESS ) phase I study is a multicenter , prospect i ve , nonr and omized trial design ed to address the question of whether carotid stenting ( CAS ) with cerebral protection is comparable to carotid endarterectomy ( CEA ) in patients with symptomatic and asymptomatic carotid stenosis . METHODS Patients with symptomatic ( with > 50 % stenosis ) or asymptomatic ( with > 75 % stenosis ) carotid stenosis were entered into the study in a 2:1 ratio of carotid stent and GuardWire Plus distal protection device . This unique trial model was developed through collaboration with the International Society of Endovascular Specialists , the Food and Drug Administration , the Centers for Medicare and Medicaid Services , the National Institutes of Health , and industry representatives . The primary end points included death and stroke at 30 days and a composite 1-year end point of death , stroke , or myocardial infa rct ion ( MI ) from 0 to 30 days and death or stroke from 31 days to 1 year . The secondary end points included residual stenosis , restenosis , repeat angiography , and carotid revascularization at 30 days and 1 year and quality -of-life changes at 1 year . RESULTS A total of 397 patients ( 254 CEA and 143 CAS ) were enrolled in the study : 32 % were symptomatic and 68 % were asymptomatic . There were no significant differences in patient characteristics , symptoms , or surgical risk profiles between groups at baseline . Kaplan-Meier analysis revealed no significant differences in combined death/stroke rates at 30 days ( 3.6 % CEA vs 2.1 % CAS ) or at 1 year ( 13.6 % CEA vs 10.0 % CAS ) . Similarly , there was no significant difference in the combined end point of death , stroke , or MI at 30 days ( 4.4 % CEA vs 2.1 % CAS ) or at 1 year ( 14.3 % CEA vs 10.9 % CAS ) . There were no significant differences between CEA and CAS in the secondary end points of residual stenosis ( 0 % CEA vs 0.9 % CAS ) , restenosis ( 3.6 % CEA vs 6.3 % CAS ) , repeat angiography ( 2.1 % CEA vs 3.6 % CAS ) , carotid revascularization ( 1.0 % CEA vs 1.8 % CAS ) , or change in quality of life ( -1.56 points CEA vs -4.22 points CAS ) . CONCLUSIONS The CaRESS phase I study suggests that the 30-day and 1-year risk of death , stroke , or MI with CAS is equivalent to that with CEA in symptomatic and asymptomatic patients with carotid stenosis BACKGROUND Among patients with substantial carotid artery narrowing but no recent neurological symptom ( stroke or transient ischaemia ) , the balance of surgical risks and long-term benefits from carotid endarterectomy ( CEA ) was unclear . METHODS During 1993 - 2003 , 3120 asymptomatic patients with substantial carotid narrowing were r and omised equally between immediate CEA ( half got CEA by 1 month , 88 % by 1 year ) and indefinite deferral of any CEA ( only 4 % per year got CEA ) and were followed for up to 5 years ( mean 3.4 years ) . Kaplan-Meier analyses of 5-year risks are by allocated treatment . FINDINGS The risk of stroke or death within 30 days of CEA was 3.1 % ( 95 % CI 2.3 - 4.1 ) . Comparing all patients allocated immediate CEA versus all allocated deferral , but excluding such perioperative events , the 5-year stroke risks were 3.8 % versus 11 % ( gain 7.2 % [ 95 % CI 5.0 - 9.4 ] , p<0.0001 ) . This gain chiefly involved carotid territory ischaemic strokes ( 2.7 % vs 9.5 % ; gain 6.8 % [ 4.8 - 8.8 ] , p<0.0001 ) , of which half were disabling or fatal ( 1.6 % vs 5.3 % ; gain 3.7 % [ 2.1 - 5.2 ] , p<0.0001 ) , as were half the perioperative strokes . Combining the perioperative events and the non-perioperative strokes , net 5-year risks were 6.4 % versus 11.8 % for all strokes ( net gain 5.4 % [ 3.0 - 7.8 ] , p<0.0001 ) , 3.5 % versus 6.1 % for fatal or disabling strokes ( net gain 2.5 % [ 0.8 - 4.3 ] , p=0.004 ) , and 2.1 % versus 4.2 % just for fatal strokes ( net gain 2.1 % [ 0.6 - 3.6 ] , p=0.006 ) . Subgroup-specific analyses found no significant heterogeneity in the perioperative hazards or ( apart from the importance of cholesterol ) in the long-term postoperative benefits . These benefits were separately significant for males and females ; for those with about 70 % , 80 % , and 90 % carotid artery narrowing on ultrasound ; and for those younger than 65 and 65 - 74 years of age ( though not for older patients , half of whom die within 5 years from unrelated causes ) . Full compliance with allocation to immediate CEA or deferral would , in expectation , have produced slightly bigger differences in the numbers operated on , and hence in the net 5-year benefits . The 10-year benefits are not yet known . INTERPRETATION In asymptomatic patients younger than 75 years of age with carotid diameter reduction about 70 % or more on ultrasound ( many of whom were on aspirin , antihypertensive , and , in recent years , statin therapy ) , immediate CEA halved the net 5-year stroke risk from about 12 % to about 6 % ( including the 3 % perioperative hazard ) . Half this 5-year benefit involved disabling or fatal strokes . But , outside trials , inappropriate selection of patients or poor surgery could obviate such benefits Background and Purpose — The German Societies of Angiology and Radiology have instituted a prospect i ve registry of carotid angioplasty and stenting ( CAS ) to limit uncontrolled use of CAS and to collect data about technique and results of CAS outside clinical trials . Methods — A total of 38 centers register their patients prospect ively before CAS is performed . At discharge , technical details , periprocedural medication , and the clinical course are reported on a st and ardized form . Results — During the first 48 months , 3853 planned interventions were recorded , and CAS was actually attempted on 3267 patients of whom 1827 ( 56 % ) were symptomatic and 1433 ( 44 % ) were asymptomatic . In 3127 ( 98 % ) cases , stents were used , of which 2784 ( 89 % ) were of the self-exp and ing type . Other technical aspects such as the use of guiding catheters and protection devices varied widely among the centers . Periprocedural medication rather uniformly included aspirin and clopidogrel before and after CAS and high-dose heparin and atropin during CAS . CAS was successful in 3207 ( 98 % ) cases . There was a 0.6 % ( n=18 ) mortality rate , a 1.2 % ( n=38 ) major stroke rate , and a 1.3 % ( n=41 ) minor stroke rate . The combined stroke and death rate was 2.8 % ( n=90 ) . Conclusions — These prospect i ve multicenter data are likely to give a realistic picture of the possibilities and limitations of CAS in the general community . They suggest that CAS may be performed with similar results in the general community as they have been reported by highly specialized centers and in clinical studies BACKGROUND Without strong evidence of benefit , the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s , then declined . Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis . METHODS We conducted a r and omized trial at 50 clinical centers throughout the United States and Canada , in patients in two predetermined strata based on the severity of carotid stenosis--30 to 69 percent and 70 to 99 percent . We report here the results in the 659 patients in the latter stratum , who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery . All patients received optimal medical care , including antiplatelet therapy . Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons . All patients were examined by neurologists 1 , 3 , 6 , 9 , and 12 months after entry and then every 4 months . End points were assessed by blinded , independent case review . No patient was lost to follow-up . RESULTS Life-table estimates of the cumulative risk of any ipsilateral stroke at two years were 26 percent in the 331 medical patients and 9 percent in the 328 surgical patients --an absolute risk reduction ( + /- SE ) 17 + /- 3.5 percent ( P less than 0.001 ) . For a major or fatal ipsilateral stroke , the corresponding estimates were 13.1 percent and 2.5 percent -- an absolute risk reduction of 10.6 + /- 2.6 percent ( P less than 0.001 ) . Carotid endarterectomy was still found to be beneficial when all strokes and deaths were included in the analysis ( P less than 0.001 ) . CONCLUSIONS Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high- grade stenosis ( 70 to 99 percent ) of the internal carotid artery OBJECTIVE To determine whether carotid endarterectomy provides protection against subsequent cerebral ischemia in men with ischemic symptoms in the distribution of significant ( greater than 50 % ) ipsilateral internal carotid artery stenosis . DESIGN Prospect i ve , r and omized , multicenter trial . SETTING Sixteen university-affiliated Veterans Affairs medical centers . PATIENTS Men who presented within 120 days of onset of symptoms that were consistent with transient ischemic attacks , transient monocular blindness , or recent small completed strokes between July 1988 and February 1991 . Among 5000 patients screened , 189 individuals were r and omized with angiographic internal carotid artery stenosis greater than 50 % ipsilateral to the presenting symptoms . Forty-eight eligible patients who refused entry were followed up outside of the trial . OUTCOME MEASURES Cerebral infa rct ion or crescendo transient ischemic attacks in the vascular distribution of the original symptoms or death within 30 days of r and omization . INTERVENTION Carotid endarterectomy plus the best medical care ( n = 91 ) vs the best medical care alone ( n = 98 ) . RESULTS At a mean follow-up of 11.9 months , there was a significant reduction in stroke or crescendo transient ischemic attacks in patients who received carotid endarterectomy ( 7.7 % ) compared with nonsurgical patients ( 19.4 % ) , or an absolute risk reduction of 11.7 % ( P = .011 ) . The benefit of surgery was more profound in patients with internal carotid artery stenosis greater than 70 % ( absolute risk reduction , 17.7 % ; P = .004 ) . The benefit of surgery was apparent within 2 months after r and omization , and only one stroke was noted in the surgical group beyond the 30-day perioperative period . CONCLUSIONS For a selected cohort of men with symptoms of cerebral or retinal ischemia in the distribution of a high- grade internal carotid artery stenosis , carotid endarterectomy can effectively reduce the risk of subsequent ipsilateral cerebral ischemia . The risk of cerebral ischemia in this subgroup of patients is considerably higher than previously estimated BACKGROUND Carotid endarterectomy is the st and ard of care for most patients with severe extracranial carotid bifurcation disease . However , its safety and efficacy in patients with significant surgical risk are unclear . The ARCHeR ( ACCULINK for Revascularization of Carotids in High-Risk patients ) trial was performed to determine whether carotid artery stenting with embolic protection is a safe and effective alternative to endarterectomy in high-surgical-risk patients . METHODS The ARCHeR trial is a series of three sequential , multicenter , nonr and omized , prospect i ve studies . Forty-eight sites enrolled 581 high-surgical-risk patients between May 2000 and September 2003 . Patients with severe carotid artery stenosis ( angiographically defined , symptomatic > or = 50 % , or asymptomatic > or = 80 % ) had an ACCULINK nitinol stent implanted . The ACCUNET filter embolic protection system was added to the procedure in the final 2 studies ( 422 patients ) . The primary efficacy end point was a composite of periprocedural ( < or = 30 days ) death , stroke , and myocardial infa rct ion , plus ipsilateral stroke between days 31 and 365 . RESULTS The 30-day rate of death/stroke/myocardial infa rct ion was 8.3 % ( 95 % confidence interval [ CI ] , 6.2%-10.8 % ) , and that of stroke/death was 6.9 % ( 95 % CI , 5.0%-9.3 % ) . Most ( 23/32 ) strokes were minor , of which more than half ( 12/23 ) returned to baseline National Institutes of Health Stroke Scale scores within 30 days . The 30-day major/fatal stroke rate was 1.5 % ( 95 % CI , 0.7%-2.9 % ) . No hemorrhagic strokes were observed in the study . Ipsilateral cerebrovascular accident occurred in 1.3 % between 30 days and 1 year , thus giving a primary composite end point of 30-day death/stroke/myocardial infa rct ion plus ipsilateral stroke at 1 year of 9.6 % ( 95 % CI , 7.2%-12.0 % ) , which is below the 14.4 % historical control comparator . Target lesion revascularization at 12 months and 2 years was 2.2 % and 2.9 % , respectively . CONCLUSIONS The ARCHeR results demonstrate that extracranial carotid artery stenting with embolic filter protection is not inferior to historical results of endarterectomy and suggest that carotid artery stenting is a safe , durable , and effective alternative in high-surgical-risk patients BACKGROUND Carotid angioplasty ( CA ) has been suggested to be a safer and more cost-effective alternative to carotid endarterectomy ( CEA ) in the management of symptomatic severe internal carotid artery ( ICA ) disease . METHODS The study was conducted as a prospect i ve consecutive r and omized trial of CEA versus CA for symptomatic severe ICA disease in a university teaching hospital . All patients were assessed before and after surgery by a neurologist . The study consisted of 23 patients with focal carotid territory symptoms and severe ICA stenosis ( > 70 % ) who were r and omized to either CEA or CA . However , only 17 had received their allocated treatment before trial suspension . CEA with patching or CA with stenting were used as interventions . The main outcome measures were death or disabling or nondisabling stroke within 30 days . RESULTS All 10 CEA operations proceeded without complication , but 5 of the 7 patients who underwent CA had a stroke ( P=.0034 ) , 3 of which were disabling at 30 days . CONCLUSIONS After referral , the Data Monitoring Committee invoked the stopping rule and the trial was suspended . The investigators and the Ethics Committee subsequently concluded that the trial could not be restarted -- even in an amended format-primarily because of problems with informed consent . We review many of the ethical dilemmas encountered in the performance of this study . If future trials do suggest a selected role for CA , it is essential that both the inclusion and the exclusion criteria are fully documented OBJECTIVE Carotid endarterectomy ( CEA ) is effective in reducing the risk of stroke in individuals with more than 60 % carotid stenosis . Carotid angioplasty and stenting ( CAS ) has been proffered as effective and used in treating individuals with asymptomatic carotid stenosis despite the absence of proven clinical equivalency . This r and omized trial was design ed to explore the hypothesis that CAS is equivalent to CEA for treating asymptomatic carotid stenosis . METHODS A total of 85 individuals presenting with asymptomatic carotid stenosis of more than 80 % were selected r and omly for CAS or CEA and followed up for 48 months . RESULTS Stenosis decreased to an average of 5 % after CAS . The patency of the reconstructed artery remained satisfactory regardless of the technique , as determined by carotid ultrasonography . No major complications such as cerebral ischemia or death occurred . Procedural complications associated with CAS ( n = 5 ) were hypotension and /or bradycardia ; those concomitant with CEA ( n = 3 ) were cervical nerve injury or complications related to general anesthesia ( n = 4 ) . Both procedures were well tolerated in the context of pain and discomfort . Hospital stay was similar in the two groups ( mean , 1.1 versus 1.2 d ) . The occurrence of complications associated with CAS or CEA prolonged hospitalization by 3 days ( mean , 4.0 versus 4.5 d ) . Return to full activity was achieved within 1 week by more than 85 % of patients ; all returned to their usual lifestyle by 2 weeks . Although hospital charges were slightly higher for CAS , costs were similar . CONCLUSION CAS and CEA may be equally effective and safe in treating individuals with asymptomatic carotid stenosis AIM Although the first long-term results of Carotid Artery Stenting ( CAS ) became available only recently , CAS has become an accepted treatment for carotid artery disease . We report CAS data up to 5 years , both late stroke rate and patency rates as observed in 4 high-volume European centers . METHODS Between February 1 , 1993 and December 31 , 2004 , 2 172 patients were selected over the 4 participating centres , with intention to treat endovascularly . Conscientious follow-up was done according to the in-hospital stipulations of each centre and was entered into a data base both retrospectively and prospect ively . Long-term restenosis and stroke-death rates were investigated and statistically analysed and stratified using the Kaplan-Meier method . RESULTS Of the 2 172 patients with intention to treat 2 165 ( 99.7 % ) were technically successful . Of these 306 ( 14.1 % ) were performed without and 1 859 ( 85.9 % ) with embolic protection device ( EPD ) ; 96 patients ( 4.4 % ) received balloon dilation only and stenting was performed in 2 069 ( 95.6 % ) cases . Kaplan-Meier analysis of major stroke/all death and of significant restenosis ( > 50 % ) for the total population showed stroke/death rates of 4.1 % ( nar=1 356 ) , 10.1 % ( nar=476 ) and 15.5 % ( nar=138 ) ; and restenosis rates of 1 % ( nar=1 363 ) , 2 % ( nar=480 ) and 3.4 % ( nar=139 ) , after 1 , 3 and 5 years respectively . CONCLUSIONS The patency and stroke/death rates result ing from our data base analysis are pleasing and indicate that CAS also on longer term is a valuable treatment method for carotid artery disease . Due to the fact that our data set contains prospect i ve as well as retrospective data , it may have its limitations . Until this moment , data indicating that certain patient subgroups are at increased risk for neurological complications and in-stent restenosis during and after CAS are sparse . Further multivariant analysis on this unique data set is m and atory in order to identify any potential links in between plaque morphology , preprocedural neurological complications , risk factor distribution , procedural steps and clinical outcome OBJECTIVES The goal of this study was to determine whether carotid angioplasty and stenting ( CAS ) is equivalent to carotid endarterectomy ( CEA ) in patients with symptomatic carotid stenosis > 70 % by a r and omized , controlled trial in a community hospital . BACKGROUND Carotid angioplasty and stenting has been suggested to be as effective as CEA for treatment of symptomatic carotid artery stenosis . METHODS A total of 104 patients presenting with cerebrovascular ischemia ipsilateral to carotid stenosis were selected r and omly for CEA or carotid stenting and followed for two years . RESULTS Stenosis decreased to an average of 5 % after CAS . The patency of the reconstructed artery remained satisfactory regardless of the technique as determined by sequential ultrasound . One death occurred in the CEA group ( 1/51 ) ; one transient ischemic attack occurred in the CAS group ( 1/53 ) ; no individual sustained a stroke . The perception of procedurally related pain/discomfort was similar . Hospital stay was similar , although the CAS group tended to be discharged earlier ( mean = 1.8 days vs. 2.7 days ) . Complications associated with CAS prolonged hospitalization when compared with those sustaining a CEA-related complication ( mean = 5.6 days vs. 3.8 days ) . Return to full activity was achieved within one week by 80 % of the CAS group and 67 % of the patients receiving CEA . Hospital charges were slightly higher for CAS . CONCLUSIONS Carotid stenting is equivalent to CEA in reducing carotid stenosis without increased risk for major complications of death/stroke . Because of shortened hospitalization and convalescence , CAS challenges CEA as the preferred treatment of symptomatic carotid stenosis if a reduction in costs can be achieved Purpose : To evaluate the feasibility and safety of carotid artery stenting ( CAS ) performed by a dedicated multidisciplinary team in a community hospital . Methods : Forty-nine patients ( 30 men ; mean age 74.3 ± 7.4 years , range 51–88 ) with 14 symptomatic and 35 asymptomatic > 50 % carotid stenoses were enrolled into the study and treated with self-exp and ing stents without cerebral protection . The patients were evaluated at 30 days for death , neurological sequelae , and length of stay . A contemporaneous group of 140 patients ( 80 men ; mean age 72.3 ± 7.7 years , range 43–89 ) undergoing carotid endarterectomy ( CEA ) was used for comparison of the outcome measures . Owing to crossover of failed CAS patients to the CEA group , the data were analyzed according to intention-to-treat and treatment-received . Results : The only difference in baseline characteristics between the treatment and control groups was the greater frequency of bilateral disease in the CEA group ( p=0.009 ) . The CAS procedures were successful in 47 ( 96.0 % ) patients ; 2 access failures were converted to endarterectomy , and 1 access-site pseudoaneurysm was treated surgically . There were no deaths or myocardial infa rct ions in either group . In the CAS group , there were no major and only 2 ( 4.1 % ) minor strokes compared to 4 ( 2.9 % ) major and 4 ( 2.9 % ) minor strokes in the CEA group ( p>0.05 ) . Median LOS was significantly lower in the CAS group ( p<0.0001 ) . Conclusions : Careful case selection and multidisciplinary collaboration facilitate the safe performance of carotid stenting in a community setting with acceptable early results BACKGROUND Previous studies have shown that carotid endarterectomy in patients with symptomatic severe carotid stenosis ( defined as stenosis of 70 to 99 percent of the luminal diameter ) is beneficial up to two years after the procedure . In this clinical trial , we assessed the benefit of carotid endarterectomy in patients with symptomatic moderate stenosis , defined as stenosis of less than 70 percent . We also studied the durability of the benefit of endarterectomy in patients with severe stenosis over eight years of follow-up . METHODS Patients who had moderate carotid stenosis and transient ischemic attacks or nondisabling strokes on the same side as the stenosis ( ipsilateral ) within 180 days before study entry were stratified according to the degree of stenosis ( 50 to 69 percent or < 50 percent ) and r and omly assigned either to undergo carotid endarterectomy ( 1108 patients ) or to receive medical care alone ( 1118 patients ) . The average follow-up was five years , and complete data on outcome events were available for 99.7 percent of the patients . The primary outcome event was any fatal or nonfatal stroke ipsilateral to the stenosis for which the patient underwent r and omization . RESULTS Among patients with stenosis of 50 to 69 percent , the five-year rate of any ipsilateral stroke ( failure rate ) was 15.7 percent among patients treated surgically and 22.2 percent among those treated medically ( P=0.045 ) ; to prevent one ipsilateral stroke during the five-year period , 15 patients would have to be treated with carotid endarterectomy . Among patients with less than 50 percent stenosis , the failure rate was not significantly lower in the group treated with endarterectomy ( 14.9 percent ) than in the medically treated group ( 18.7 percent , P=0.16 ) . Among the patients with severe stenosis who underwent endarterectomy , the 30-day rate of death or disabling ipsilateral stroke persisting at 90 days was 2.1 percent ; this rate increased to only 6.7 percent at 8 years . Benefit was greatest among men , patients with recent stroke as the qualifying event , and patients with hemispheric symptoms . CONCLUSIONS Endarterectomy in patients with symptomatic moderate carotid stenosis of 50 to 69 percent yielded only a moderate reduction in the risk of stroke . Decisions about treatment for patients in this category must take into account recognized risk factors , and exceptional surgical skill is obligatory if carotid endarterectomy is to be performed . Patients with stenosis of less than 50 percent did not benefit from surgery . Patients with severe stenosis ( > or = 70 percent ) had a durable benefit from endarterectomy at eight years of follow-up The European Carotid Surgery Trial is a multicentre trial of carotid endarterectomy for patients who , after a carotid territory non-disabling ischaemic stroke , transient ischaemic attack , or retinal infa rct , are found to have a stenotic lesion in the relevant ( ipsilateral ) carotid artery . Over the past 10 years 2518 patients have been r and omised , and the mean follow-up is now almost 3 years among the 2200 thus far available for analysis of the incidence of strokes that lasted more than 7 days . For the patients with " moderate " ( 30 - 69 % ) stenosis on their prer and omisation angiogram the balance of surgical risk and eventual benefit remains uncertain , and full recruitment continues . For 374 patients with only " mild " ( 0 - 29 % ) stenosis there was little 3-year risk of ipsilateral ischaemic stroke , even in the absence of surgery , so any 3-year benefits of surgery were small , and were outweighed by its early risks . For 778 patients with " severe " ( 70 - 99 % ) stenosis , however , the risks of surgery were significantly outweighed by the later benefits : although 7.5 % had a stroke ( or died ) within 30 days of surgery , during the next 3 years the risks of ipsilateral ischaemic stroke were ( by life-table analysis ) an extra 2.8 % for surgery-allocated and 16.8 % for control patients ( a sixfold reduction , p less than 0.0001 ) . There was also a small reduction in other strokes , and at 3 years the total risk of surgical death , surgical stroke , ipsilateral ischaemic stroke , or any other stroke was 12.3 % for surgery and 21.9 % for control ( difference 9.6 % SD 3.3 , 2p less than 0.01 ) . The main concern was to avoid disabling or fatal events , and , among severe stenosis patients , 3.7 % had a disabling stroke ( or died ) within 30 days of surgery , an extra 1.1 % surgery versus 8.4 % control ( p less than 0.0001 ) had a disabling or fatal ipsilateral ischaemic stroke by 3 years , and the total 3-year risk of any disabling or fatal stroke ( or surgical death ) was 6.0 % surgery versus 11.0 % control ( overall difference 5.0 % SD 2.3 , 2p less than 0.05 ) ; but , for disabling or fatal stroke the control risks seemed to diminish after the first year , so delay of surgery by just a few months after clinical presentation might make this overall difference non-significant |
1,692 | 23,183,871 | Conclusions On the basis of evidence of both r and omized and prospect i ve controlled series , mortality and morbidity RR , including subgroup analysis , were significantly lower after laparoscopic compared to open surgery | Background Although definitive long-term results are not yet available , the global safety of laparoscopic surgery for rectal cancer treatment remains controversial .
We evaluated differences in the safety of laparoscopic rectal resection versus open surgery for cancer . | Background The role of laparoscopic resection ( LR ) in the management of extraperitoneal rectal cancer still is unclear . This study aim ed to compare perioperative and long-term results of laparoscopic and open resection ( OR ) for low and midrectal cancer . Methods A prospect i ve nonr and omized trial comparing patients su bmi tted to OR or LR for low and midrectal cancer at a single institution was conducted . Results The study included 191 consecutive patients : 98 patients who underwent LR and 93 who underwent OR . The mean follow-up period was 46.3 months for LR and 49.7 months for OR . The conversion rate for LR was 18.4 % . With the use of LR , the mean time for complete patient mobilization was shorter ( 1.7 vs 3.3 days ; p < 0.001 ) and patients were earlier in passing flatus ( 2.6 vs 3.9 days ; p < 0.001 ) and stools ( 3.8 vs 4.7 days ; p < 0.01 ) , and in resuming oral intake ( 3.4 vs 4.8 days ; p < 0.001 ) . The mean hospital stay was shorter for LR , but the difference did not reach significance ( 11.4 vs 13 days ) . Morbidity and mortality rates were similar : LR ( 24.4 % and 1 % ) and OR ( 23.6 % and 2.2 % ) . Laparoscopic patients presented a higher rate of anastomotic fistulas ( 13.5 % vs 5.1 % ) and reoperations ( 6.1 % vs 3.2 % ) but the difference was statistically nonsignificant . Laparoscopic resection presented a significantly lower local recurrence rate ( 3.2 % vs 12.6 % ; p < 0.05 ) . The cumulative survival and disease-free rates at 5 years were , respectively , 80 % and 65.4 % after LR and 68.9 % and 58.9 % after OR ( nonsignificant difference ) . Stage-by-stage comparison showed prolonged cumulative survival for stages III and IV cancer in LR ( 82.5 % vs 40.5 % ; p = 0.006 and 15.8 % vs 0 % ; p = 0.013 , respectively ) and a reduced rate of cancer-related death for stage III in LR ( 11.4 % vs 51.9 % ; p = 0.001 ) . Conclusions As compared with conventional open surgery , LR for low and midrectal cancer is characterized by a faster recovery and similar overall morbidity ( but a higher rate of anastomotic leakages ) , and does not present any adverse oncologic effect Purpose Laparoscopic surgery of colon cancer has been accepted to be oncologically adequate compared with open resection . However , the situation in rectal cancer remains unclear , because anatomy and complex surgical procedures might specifically influence the long-term outcome . This study was design ed to analyze perioperative and long-term outcome of patients with rectal cancer after laparoscopic vs. open access surgery . Methods A total of 389 patients ( 1998–2005 ) were prospect ively analyzed ; 114 patients had laparoscopic beginning , and 25 patients had conversion and were separately analyzed . Eighty-nine patients remained in the laparoscopic group and 275 had open access surgery . Results Both groups were comparable regarding age , gender , tumor localization , stage , and complications . Differences were found in harvested lymph nodes ( laparoscopic 13.5/open access 16.9 ; P = 0.001 ) and hospitalization ( 15.1/18.7 days ; P = 0.037 ) . Local recurrence rate and metachronous metastasis were comparable . In patients with deep anterior resection with total mesenteric excision , favorable long-term survival in the laparoscopic group was found ( P = 0.035 , log-rank ) . Conclusions Minimally invasive surgery is equivalent in the treatment of rectal cancer and shows advantages of shorter hospitalization and faster recovery . Especially in patients with low rectal cancer , minimally invasive surgery with exact preparation of the total mesenteric excision seems to be favorable compared with open access surgery Purpose This study was design ed to evaluate the impact of laparoscopic rectal resection on short-term postoperative morbidity and costs . Methods A total of 168 patients with rectal cancer were r and omly assigned to laparoscopic ( n = 83 ) or open ( n = 85 ) resection . Outcome parameters were : postoperative morbidity , length of hospital stay , quality of life , long-term survival , and local recurrences . The mean follow-up period was 53.6 months . Cost-benefit analysis was based on hospital costs . Results Operative time was 53 minutes longer in the laparoscopic group ( P < 0.0001 ) . Postoperative morbidity rate was 28.9 percent in the laparoscopic vs. 40 percent in the open group ( P = 0.18 ) . The mean length of hospital stay was 10 ( 4.9 ) days in the laparoscopic group and 13.6 ( 10 ) days in the open group ( P = 0.004 ) . Local recurrence rate and five-year survival were similar in both groups ; however , the limited number of patients does not allow firm conclusions . Quality of life was better in the laparoscopic group only in the first year after surgery ( P < 0.0001 ) . The additional charge in the laparoscopic group was $ 1,748 per patient r and omized ( $ 1,194 the result of surgical instruments and $ 554 the result of longer operative time ) . The saving in the laparoscopic group was $ 1,396 per patient r and omized ( $ 647 the result of shorter length of hospital stay and $ 749 the result of the lower cost of postoperative complications ) . The net balance result ed in $ 351 extra cost per patient r and omly allocated to the laparoscopic group . Conclusions Short-term postoperative morbidity was similar in the two groups . Laparoscopic resection reduced length of hospital stay , improved first-year quality of life , and slightly increased hospital costs BACKGROUND The safety and short-term benefits of laparoscopic colectomy for cancer remain debatable . The multicentre COLOR ( COlon cancer Laparoscopic or Open Resection ) trial was done to assess the safety and benefit of laparoscopic resection compared with open resection for curative treatment of patients with cancer of the right or left colon . METHODS 627 patients were r and omly assigned to laparoscopic surgery and 621 patients to open surgery . The primary endpoint was cancer-free survival 3 years after surgery . Secondary outcomes were short-term morbidity and mortality , number of positive resection margins , local recurrence , port-site or wound-site recurrence , metastasis , overall survival , and blood loss during surgery . Analysis was by intention to treat . Here , clinical characteristics , operative findings , and postoperative outcome are reported . FINDINGS Patients assigned laparoscopic resection had less blood loss compared with those assigned open resection ( median 100 mL [ range 0 - 2700 ] vs 175 mL [ 0 - 2000 ] , p<0.0001 ) , although laparoscopic surgery lasted 30 min longer than did open surgery ( p<0.0001 ) . Conversion to open surgery was needed for 91 ( 17 % ) patients undergoing the laparoscopic procedure . Radicality of resection as assessed by number of removed lymph nodes and length of resected oral and aboral bowel did not differ between groups . Laparoscopic colectomy was associated with earlier recovery of bowel function ( p<0.0001 ) , need for fewer analgesics , and with a shorter hospital stay ( p<0.0001 ) compared with open colectomy . Morbidity and mortality 28 days after colectomy did not differ between groups . INTERPRETATION Laparoscopic surgery can be used for safe and radical resection of cancer in the right , left , and sigmoid colon Abstract . Previous analyses of non- prospect ively r and omized trials have suggested that early oral postoperative feeding might be a benefit unique to laparoscopic surgery . However , some authors have indicated that early feeding can be tolerated by the majority of patients after elective open surgery . Aim : This prospect i ve r and omized study was undertaken to assess whether the time prior to oral intake of food after laparoscopy-assisted surgery is shorter than that after st and ard laparotomy . Methods : This trial included 40 patients who were divided r and omly into two groups before operation . Group I included 20 patients ( mean age , 52 years ; range , 15 – 77 years ) who underwent a laparoscopy-assisted colon or rectal procedure ( LAP ) . Group II consisted of 20 patients ( mean age , 56 years , range , 41 – 74 years ) who underwent surgery with a st and ard midline incision ( SMI ) . On the evening after surgery , patients were allowed clear liquids ab libitum . This regimen was continued until the first postoperative day at which time they could elect to start eating a regular diet . If a patient had two episodes of vomiting , a nasogastric tube was inserted . Results : Five laparoscopic procedures were converted to SMI because of adhesions ( 25 % ) and an equal number of patients was excluded from the group that was treated in the traditional manner . Therefore , only 30 patients were included in the analysis . There were no deaths in this trial . Complications appeared in four of the patients in the LAP group and in two of the patients in the SMI group ( no significant difference ) . There were no statistically significant differences between the two groups in terms of the ability to tolerate the early oral intake of food , in the frequency of vomiting or in the incidence of insertion of a nasogastric tube . The time to the first bowel movement was 5.4 days in LAP and 5.5 days in SMI , and the difference was not significant . Conclusion : This study invali date s the cl aim by laparoscopic surgeons that earlier oral intake of food is tolerated by their patients than by patients who undergo st and ard procedures .Résumé . Des études r and omisées non prospect ives ont suggéré que la reprise précoce de l'alimentation orale peut être un bénéfice particulier à la chirurgie laparoscopique . Certains auteurs ont indiqué que la reprise précoce de l'alimentation orale peut être bien tolérée par la plupart des patients après chirurgie élective ouverte . Cette étude prospect i ve r and omisée a été entreprise pour déterminer si la reprise orale de l'alimentation après chirurgie laparoscopique peut être plus précoce qu'après une laparotomie st and ard . Quarante patients ont été inclus dans cette étude et ont été divisés de manière r and omisée en deux groupes avant chirurgie . Le groupe 1 comporte 20 patients ( 15 à 77 ans , moyenne d'âge 52 ans ) qui ont subi une résection colique ou rectale laparoscopique ( LAP ) . Le groupe II comporte 20 patients ( 41 à 74 ans , moyenne d'âge 56 ans ) qui ont subi une chirurgie par une incision médiane st and ard ( SMI ) . Le soir de l'intervention chirurgicale , les patients ont été autorisés à boire librement . Ce régime a été continué le premier jour postopératoire à partir duquel les patients pouvaient débuter une alimentation normale . Si un patient présente deux épisodes de vomissements , une sonde naso-gastrique a été mise en place . Cinq interventions laparaoscopiques ont dûêtre converties en chirurgie ouverte en raison d'adhérences ( 25 % ) et un nombre égal de patients ont été exclus du groupe qui a été traité de manière traditionelle . En conséquence , 30 patients ont été inclus dans l'analyse . Aucun décès n'est à déplorer . Quatre complications sont survenues chez des patients du groupe laparoscopique et deux dans le collectif des patients ayant subi un chirurgie ouverte ( pas de différence statistique significative ) . Il n'y a pas de différence statistique significative entre les deux groupes en ce qui concerne la tolérance à la reprise orale de l'alimentation , à la fréquence des vomissements ou à la nécessité de réinsérer un tube naso-gastrique . La première exonération est survenue au 5.4 jour dans le groupe laparoscopique et au 5,5 jour dans le groupe de chirurgie ouverte sans que la différence ne soit significative . En conclusion : Cette étude infirme l'idée que la chirurgie laparoscopique permet une reprise précoce et bien tolérée de l'alimentation en comparaison à la chirrugie ouverte AIM To evaluate the feasibility of laparoscopic resection of rectal carcinoma and to compare the short-term outcome of laparoscopic procedure with conventional open surgery for rectal cancer . METHODS Thirty-eight patients with rectal cancer were included in a prospect i ve non-r and omized study . The patients were assigned to laparoscopic ( n=18 ) or open ( n=18 ) colorectal resection . Case selection , surgical technique , and clinical and pathological results were review ed . RESULTS The operative time was longer in laparoscopic resection group ( LAP ) than in open resection group ( 189+/-18 min vs 146+/-22 min , P<0.05 ) . Intraoperative blood loss and postoperative complications were less in LAP resection group than in open resection group . An earlier return of bowel motility was observed after laparoscopic surgery . The overall postoperative morbidity was 5.6 % in the LAP resection group and 27.8 % in open resection group ( P<0.05 ) . No anastomotic leakage was found in both groups . The pathologic examination showed that the length of the resected specimen , the mean number of harvested lymph nodes in laparoscopic resection group were comparable to those in open resection group . CONCLUSION Laparoscopic total mesorectal excision ( TME ) for rectal cancer is a feasible but technically dem and ing procedure . The present study demonstrates the safety of the procedure , while oncologic results are comparable to the open surgery , with a favorable short-term outcome Purpose This study was design ed to compare the outcomes of laparoscopic anterior resection with open operation for mid and upper rectal cancer . Methods A total of 265 patients who underwent elective laparoscopic or open anterior resection for cancer of the mid and upper rectum from June 2000 to December 2004 were included . Data about the patients ’ demographics , operative details , postoperative outcome , and disease status were collected prospect ively . Comparison of the outcome between laparoscopic and open resection was performed . Results The median age of the 265 patients was 69 ( range , 27–91 ) years , and laparoscopic anterior resection was performed in 98 patients ( 37 percent ) . There was no difference in the age , gender , comorbidities , and level of tumor between the two groups . The operating time was longer in the laparoscopic group ( 200 vs. 127 minutes ; P < 0.01 ) , but the blood loss was less ( 200 vs. 250 ml ; P = 0.027 ) . The overall operative mortality was 1.8 percent , and the complication rate was 27.9 percent . Significantly more patients with early diseases ( Stage I and Stage II ) were operated with laparoscopic approach . There was no difference in the mortality or morbidity between the two groups . Anastomotic leakage occurred in five patients with open resection and one with laparoscopic resection ( P = 0.418 ) . Patients with laparoscopic resection had an earlier return of bowel function and earlier resumption of diet as well as a shorter median hospital stay ( 7 vs. 8 days ; P < 0.001 ) . With the median follow-up of the surviving patients for 21.2 months , the three-year local recurrence rates for those with open and laparoscopic resection were 4.9 and 3.3 percent , respectively ( P = 0.513 ) . In patients with Stage I and Stage II disease , the three-year cancer-specific survivals for open and laparoscopic resection were 89.8 and 88.6 percent , respectively ( P = 0.882 ) , whereas those of patients with Stage III disease were 65.6 and 55.5 percent , respectively ( P = 0.911 ) . Conclusions Laparoscopic anterior resection for mid and proximal rectal cancer is a safe option with short-term advantages compared with open operation . The oncologic outcomes of patients who underwent laparoscopic anterior resection were not compromised , with similar local recurrence rate and the cancer-specific survival rate as patients who underwent open resection INTRODUCTION Because definitive long-term results are not yet available , the oncologic safety of laparoscopic surgery in rectal cancer remains controversial . Laparoscopic total mesorectal excision ( LTME ) for rectal cancer has been proposed to have several short-term advantages in comparison with open total mesorectal excision ( OTME ) . However , few prospect i ve r and omized studies have been performed . OBJECTIVES The main purpose was to evaluate whether there are relevant differences in safety and efficacy after elective LTME for the treatment of rectal cancer compared with OTME in a tertiary academic medical center . MATERIAL AND METHODS This comparative non-r and omized prospect i ve study analyzes data of 20 patients with middle and low rectal cancer treated with low anterior resection ( LAR ) or abdomino perineal resection ( APR ) from November 2005 to April 2006 . Follow-up was determined through office charts or direct patient contact . Statistical analysis was performed using chi2 test and Student 's t-test . RESULTS Ten patients underwent LTME and 10 patients underwent OTME . No conversion was required in the LTME group . Mean operating time was shorter in the laparoscopic group ( LTME ) ( 186.7 vs. 204.4 min , p < 0.007 ) . Less intraoperative blood loss and fewer postoperative complications were seen in the LTME group . An earlier return of bowel motility was achieved after laparoscopic surgery . There was no 30-day mortality and the overall morbidity was 20 % in the LTME group vs. 40 % in the OTME group . The mean number of harvested lymph nodes was greater in the laparoscopic group than in OTME group ( 10.2 + /- 2.5 vs. 8.3 + /- 3 ) . Mean follow-up time was 12 months ( range 9 - 15 months ) . No local recurrence was found . CONCLUSION LTME is a feasible procedure with acceptable postoperative morbidity and low mortality , however it is technically dem and ing . This series confirms its safety , while oncologic results are at present comparable to the OTME published series , with limitation of a short follow-up period though . Further r and omized studies are necessary to evaluate long-term clinical outcome Background The Laparoscopic approach has been applied to colorectal surgery for many years ; however , there are only a few reports on laparoscopic low and ultralow anterior resection with construction of coloanal anastomosis . This study compares open versus laparoscopic low and ultralow anterior resections , assesses the feasibility and efficacy of the laparoscopic approach of total mesorectal excision ( TME ) with anal sphincter preservation ( ASP ) , and analyzes the short-term results of patients with low rectal cancer . Methods We analyzed our experience via a prospect i ve , r and omized control trail . From June 2001 to September 2002 , 171 patients with low rectal cancer underwent TME with ASP , 82 by the laparoscopic procedure and 89 by the open technique . The lowest margin of tumors was below peritoneal reflection and 1.5–8 cm above the dentate line ( 1.5–4.9 cm in 104 cases and 5–8 cm in 67 cases ) . The grouping was r and omized . Results Results of operation , postoperative recovery , and short-term oncological follow-up were compared between 82 laparoscopic procedures and 89 controls who underwent open surgery during the same period . In the laparoscopic group , 30 patients in whom low anterior resection was performed had the anastomosis below peritoneal reflection and more than 2 cm above the dentate line , 27 patients in whom ultralow anterior resection was performed had anastomotic height within 2 cm of the dentate line , and 25 patients in whom coloanal anastomosis was performed had the anastomosis at or below the dentate line . In the open group , the numbers were 35 , 27 , and 27 , respectively . There was no statistical difference in operation time , administration of parenteral analgesics , start of food intake , and mortality rate between the two groups . However , blood loss was less , bowel function recovered earlier , and hospitalization time was shorter in the laparoscopic group . Conclusion Totally laparoscopic TME with ASP is feasible , and it is a minimally invasive technique with the benefits of much less blood loss during operation , earlier return of bowel function , and shorter hospitalization PURPOSE : The aim of the study is to assess the safety and oncologic feasibility of laparoscopic-assisted resection for rectal cancer vs open rectal resection as a phase II pilot study for a planned r and omized control trial . METHODS : A case-matched controlled prospect i ve analysis of 54 patients who underwent laparoscopic-assisted resection for stage I to III ( no T4 ) rectal cancer within 12 cm of the anal verge from 2002 to 2005 was performed . Patients were matched with contemporary patients who underwent open rectal cancer surgery ( n = 108 ) in a 1 to 2 fashion . The perioperative clinical outcomes , postoperative pathology , and oncologic outcomes were compared between the groups . RESULTS : The demographic data did not differ significantly between the groups . The laparoscopic group manifested early return of bowel function ( P = .003 ) . The complication rate was 22.2 % in the laparoscopic group and 32.4 % in the open group ( P = .178 ) . Local recurrence was similar ( 2.0 % laparoscopic , 4.2 % open , P = .417 ) . The 5-year overall and disease-free survival rate also were similar ( overall survival , 90.8 % laparoscopic , 88.5 % open , P = .261 ; disease-free survival , 80.8 % laparoscopic , 75.8 % open . P = .390 ) . CONCLUSION : The laparoscopic-assisted resection for rectal cancer was acceptable in terms of oncologic outcomes and perioperative clinical outcomes . The present data are the basis for a large-scale r and omized trial for comparison of laparoscopic and open rectal cancer surgeries ( American College of Surgeons Oncology Group Z6051 ) Background and aims Because definitive long-term results are not yet available , the oncological safety of laparoscopic surgery for treatment of rectal cancer remains unproven . The aim of this prospect i ve non-r and omised study was to assess the feasibility and short-term outcome of laparoscopic total mesorectal excision ( LTME ) after 25–30 Gy preoperative radiotherapy and to compare the results with a matched-control group of open TME ( OTME ) . Material s and methods A series of 41 patients with primary rectal cancer underwent LTME for rectal cancer and were matched with a historical control group of 41 patients who underwent OTME . Both groups received preoperative short-term radiotherapy . Results There was no mortality in the LTME group and 2 % mortality in the OTME group . The overall postoperative morbidity was 37 % in the LTME group and 51 % in the OTME group , including an anastomotic leakage of 9 and 14 % in the LTME and OTME groups respectively . A positive circumferential margin was found in 7 % of patients in the LTME group and in 12 % of the patients in the OTME group . Conclusion This study shows that LTME is technically feasible and can be performed safely . We show at least a similar surgical completeness using a laparoscopic technique compared with open surgery INTRODUCTION Laparoscopic resection of rectal cancer has been proven efficacious but morbidity and oncological outcome need to be investigated in a r and omized clinical trial . TRIAL DESIGN Non-inferiority r and omized clinical trial . METHODS The COLOR II trial is an ongoing international r and omized clinical trial . Currently 27 hospitals from Europe , South Korea and Canada are including patients . The primary endpoint is loco-regional recurrence rate three years post-operatively . Secondary endpoints cover quality of life , overall and disease free survival , post-operative morbidity and health economy analysis . RESULTS By July 2008 , 27 hospitals from the Netherl and s , Belgium , Germany , Sweden , Spain , Denmark , South Korea and Canada had included 739 patients . The intra-operative conversion rate in the laparoscopic group was 17 % . Distribution of age , location of the tumor and radiotherapy were equal in both treatment groups . Most tumors are located in the mid-rectum ( 41 % ) . CONCLUSION Laparoscopic surgery in the treatment of rectal cancer is feasible . The results and safety of laparoscopic surgery in the treatment of rectal cancer remain unknown , but are subject of interim analysis within the COLOR II trial . Completion of inclusion is expected by the end of 2009 . TRIAL REGISTRATION Clinical trials.gov , identifier : NCT00297791 ( www . clinical trials.gov ) OBJECTIVE To examine the role of total mesorectal excision in the management of rectal cancer . DESIGN A prospect i ve consecutive case series . SETTING A district hospital and referral center in Basingstoke , Engl and . PATIENTS Five hundred nineteen surgical patients with adenocarcinoma of the rectum treated for cure or palliation . INTERVENTIONS Anterior resections ( n = 465 ) with low stapled anastomoses ( 407 total mesorectal excisions ) , abdominoperineal resections ( n = 37 ) , Hartmann resections ( n = 10 ) , local excisions ( n = 4 ) , and laparotomy only ( n = 3 ) . Preoperative radiotherapy was used in 49 patients ( 7 with abdominoperineal resections , 38 with anterior resections , 3 with Hartmann resections , and 1 with laparotomy ) . MAIN OUTCOME MEASURES Local recurrence and cancer-specific survival . RESULTS Cancer-specific survival of all surgically treated patients was 68 % at 5 years and 66 % at 10 years . The local recurrence rate was 6 % ( 95 % confidence interval , 2%-10 % ) at 5 years and 8 % ( 95 % confidence interval , 2%-14 % ) at 10 years . In 405 " curative " resections , the local recurrence rate was 3 % ( 95 % confidence interval , 0%-5 % ) at 5 years and 4 % ( 95 % confidence interval , 0%-8 % ) at 10 years . Disease-free survival in this group was 80 % at 5 years and 78 % at 10 years . An analysis of histopathological risk factors for recurrence indicates only the Dukes stage , extramural vascular invasion , and tumor differentiation as variables in these results . CONCLUSIONS Rectal cancer can be cured by surgical therapy alone in 2 of 3 patients undergoing surgical excision in all stages and in 4 of 5 patients having curative resections . In future clinical trials of adjuvant chemotherapy and radiotherapy , strategies should incorporate total mesorectal excision as the surgical procedure of choice Purpose This study was design ed to compare laparoscopic vs. open total mesorectal excision for cancer of the rectum on perioperative outcome and quality of life . Methods A total of 187 consecutive unselected patients with rectal cancer who underwent total mesorectal excision during a seven-year period were prospect ively evaluated . Patients were monitored 30 days for postoperative complications . Quality of life was evaluated before and at one year after surgery . Results A total of 108 patients underwent laparoscopic total mesorectal excision , whereas 79 underwent open . Conversion rate was 12 percent . In the laparoscopic group , operating time was 33 minutes longer ( P = 0.03 ) and intraoperative blood loss was lower ( P = 0.001 ) . Tumor stage and the number of lymph nodes that were intraoperatively collected were similar in the two groups . The overall morbidity rate was 29.6 percent in the laparoscopic and 27.8 percent in the open ( P = 0.78 ) group . No patient died during the postoperative period . Anastomotic leak rate was similar in the two groups ( 14.8 percent in laparoscopic vs. 12.6 percent in open ; P = 0.88 ) . Patients in the laparoscopic group recovered earlier bowel function ( P = 0.01 ) and experienced a shorter length of stay ( P = 0.003 ) . At one-year follow-up , overall quality of life was similar in the two groups . In the laparoscopic group , social functioning item was significantly better ( P = 0.05 ) and trend to a better physical status was observed ( P = 0.07 ) . Conclusions Laparoscopic total mesorectal excision is safe and feasible , does not jeopardize the complication rate , and has the benefits of much less blood during the operation and shorter hospitalization BACKGROUND Laparoscopic total mesorectal excision ( TME ) is being used in rectal cancer more frequently . The aim of this study was to analyze the differences in short-term outcomes between open and laparoscopic TME . METHODS In this nonr and omized consecutive study , the short-term outcomes of 100 patients undergoing TME for proven rectal cancer were analyzed . RESULTS Two groups of 50 patients underwent an open or laparoscopic TME for rectal cancer . Both groups were comparable . Laparoscopic surgery took longer to perform ( 250 vs. 197.5 min , p < 0.01 ) , but was accompanied by less blood loss ( 350 vs. 800 ml , p < 0.01 ) . Enteric function recovered sooner after laparoscopy . The numbers of major and minor complications were comparable between both groups , although fewer patients had major complications in the laparoscopic group ( 6 vs. 15 patients , p = 0.03 ) . Hospital stay was shorter for patients who underwent a laparoscopic abdominoperineal resection ( 10 vs. 12 days , p = 0.04 ) . Median follow-up was 17 months for the laparoscopic group and 22 months for the open group . Survival analyses between the groups showed no statistical difference in disease-free and overall survival . CONCLUSION This study shows that laparoscopic TME for rectal cancer is a safe and feasible technique with some short-term benefits over open TME Abstract PURPOSE : This study was conducted to investigate the feasibility of laparoscopic resection of rectal cancer and to compare early outcome data with the results of the conventional technique . METHODS : From January 1996 to March 2002 , 435 patients with primary rectal cancer were operated on at our institution . Low-risk , small rectal tumors treatable by local excision , rectal cancer recurrences , and emergency cases were excluded from the analysis . Three hundred thirty-four patients were operated on by the conventional open approach . One hundred one selected patients underwent surgery by the laparoscopic technique . RESULTS : Because of the selection process , significantly more patients with early tumor stages were operated on by laparoscopy . There were no differences in mean operation time , morbidity , mortality , or the anastomotic leakage rate ; however , the need for intraoperative transfusion , mean stay in the intensive care unit , and length of hospital stay were reduced significantly . CONCLUSIONS : In terms of the intraoperative and early postoperative course , the laparoscopic resection of rectal cancer in a selected cohort of patients compares favorably with the open technique . Because follow- up time is limited to date , only very preliminary information can be given on tumor-related outcome data . However , these preliminary data appear to suggest that rectal cancer resection can be performed by laparoscopy in accordance with established principles of cancer therapy and that port-site metastases are not a relevant clinical problem . Prospect i ve , r and omized trials are required to determine whether the laparoscopic approach will play a significant role in the treatment of rectal cancer in the future BACKGROUND The safety and short-term efficacy of laparoscopic surgery for rectal cancer after preoperative chemoradiotherapy has not been demonstrated . The aim of the r and omised Comparison of Open versus laparoscopic surgery for mid and low REctal cancer After Neoadjuvant chemoradiotherapy ( COREAN ) trial was to compare open surgery with laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy . METHODS Between April 4 , 2006 , and Aug 26 , 2009 , patients with cT3N0 - 2 mid or low rectal cancer without distant metastasis after preoperative chemoradiotherapy were enrolled at three tertiary-referral hospitals . Patients were r and omised 1:1 to receive either open surgery ( n=170 ) or laparoscopic surgery ( n=170 ) , stratified according to sex and preoperative chemotherapy regimen . Short-term outcomes assessed were involvement of the circumferential resection margin , macroscopic quality of the total mesorectal excision specimen , number of harvested lymph nodes , recovery of bowel function , perioperative morbidity , postoperative pain , and quality of life . Analyses were based on the intention-to-treat population . Patients continue to be followed up for the primary outcome ( 3-year disease-free survival ) . This study is registered with Clinical Trials.gov , number NCT00470951 . FINDINGS Two patients ( 1.2 % ) in the laparoscopic group were converted to open surgery , but were included in the laparoscopic group for analyses . Estimated blood loss was less in the laparoscopic group than in the open group ( median 217.5 mL [ 150.0 - 400.0 ] in the open group vs 200.0 mL [ 100.0 - 300.0 ] in the laparoscopic group , p=0.006 ) , although surgery time was longer in the laparoscopic group ( mean 244.9 min [ SD 75.4 ] vs 197.0 min [ 62.9 ] , p<0.0001 ) . Involvement of the circumferential resection margin , macroscopic quality of the total mesorectal excision specimen , number of harvested lymph nodes , and perioperative morbidity did not differ between the two groups . The laparoscopic surgery group showed earlier recovery of bowel function than the open surgery group ( time to pass first flatus , median 38.5 h [ 23.0 - 53.0 ] vs 60.0 h [ 43.0 - 73.0 ] , p<0.0001 ; time to resume a normal diet , 85.0 h [ 66.0 - 95.0 ] vs 93.0 h [ 86.0 - 121.0 ] , p<0.0001 ; time to first defecation , 96.5 h [ 70.0 - 125.0 ] vs 123 h [ 94.0 - 156.0 ] , p<0.0001 ) . The total amount of morphine used was less in the laparoscopic group than in the open group ( median 107.2 mg [ 80.0 - 150.0 ] vs 156.9 mg [ 117.0 - 185.2 ] , p<0.0001 ) . 3 months after proctectomy or ileostomy takedown , the laparoscopic group showed better physical functioning score than the open group ( 0.501 [ n=122 ] vs -4.970 [ n=128 ] , p=0.0073 ) , less fatigue ( -5.659 [ n=122 ] vs 0.098 [ n=129 ] , p=0.0206 ) , and fewer micturition ( -2.583 [ n=122 ] vs 4.725 [ n=129 ] , p=0.0002 ) , gastrointestinal ( -0.400 [ n=122 ] vs 4.331 [ n=129 ] , p=0.0102 ) , and defecation problems ( 0.535 [ n=103 ] vs 5.327 [ n=99 ] , p=0.0184 ) in repeated measures analysis of covariance , adjusted for baseline values . INTERPRETATION Laparoscopic surgery after preoperative chemoradiotherapy for mid or low rectal cancer is safe and has short-term benefits compared with open surgery ; the quality of oncological resection was equivalent BACKGROUND The long-term survival and safety of laparoscopic surgery in patients with rectal cancer remain unclear . The aim of this trial was to assess the efficacy and safety of laparoscopic surgery for treatment of rectal cancer . METHODS We undertook a r and omized , controlled trial in 343 patients with rectal cancer between May 2004 and April 2008 . One hundred sixty-nine patients were r and omly assigned to laparoscopic surgery and 174 patients to open surgery . The main endpoint was 3-year survival . Data were analyzed according to the intention-to-treat principle . RESULTS Laparoscopic surgery was associated with earlier recovery of bowel movement compared with open surgery . The average time to first discharge , bowel movement , resumption of fluid intake , and activity out of bed in laparoscopic surgery were shorter by 0.63 , 0.32 , 0.33 , and 0.63 day , respectively ( P < .001 ) . The incidences of postoperative morbidities such as infectious complications , anastomotic leakage , anastomotic stenosis , and deep vein thrombosis have no differences . No differences were found in the comparison of long-term survival . INTERPRETATION Laparoscopic surgery for rectal cancer is as safe and effective as open surgery in terms of oncology outcomes . Long-term survival for patients with rectal cancer undergoing laparoscopic surgery were similar to those undergoing conventional open surgery , thus supporting the continued use of laparoscopic surgery in Chinese patients with rectal cancer Background Laparoscopic resection of colonic cancer has been shown to improve postoperative recovery without jeopardizing tumor clearance and survival , but information on low rectal cancer is scarce . The aim of this r and omized trial was to compare postoperative recovery between laparoscopic-assisted versus open abdominoperineal resection ( APR ) in patients with low rectal cancer . Recurrence and survival data were also recorded and compared between the two groups . Methods Between September 1994 and February 2005 , 99 patients with low rectal cancer were r and omized to receive either laparoscopic-assisted ( 51 patients ) or conventional open ( 48 patients ) APR . The median follow-up time of living patients was about 90 months for both groups . The primary and secondary endpoints of the study were postoperative recovery and survival , respectively . Data were analyzed by intention-to-treat principle . Results The demographic data of the two groups were comparable . Postoperative recovery was better after laparoscopic surgery , with earlier return of bowel function ( P < .001 ) and mobilization ( P = .005 ) , and less analgesic requirement ( P = .007 ) . This was at the expense of longer operative time and higher direct cost . There were no differences in morbidity and operative mortality rates between the two groups . After curative resection , the probabilities of survival at 5 years of the laparoscopic-assisted and open groups were 75.2 % and 76.5 % respectively ( P = .20 ) . The respective probabilities of being disease-free were 78.1 % and 73.6 % ( P = .55 ) . Conclusions Laparoscopic-assisted APR improves postoperative recovery and seemingly does not jeopardize survival when compared with open surgery for low rectal cancer . A larger sample size is needed to fully assess oncological outcomes BACKGROUND Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale r and omised trials to support its use . We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes . METHODS Between July , 1996 , and July , 2002 , we undertook a multicentre , r and omised clinical trial in 794 patients with colorectal cancer from 27 UK centres . Patients were allocated to receive laparoscopic-assisted ( n=526 ) or open surgery ( n=268 ) . Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins , proportion of Dukes ' C2 tumours , and in-hospital mortality . Analysis was by intention to treat . This trial has been assigned the International St and ard R and omised Controlled Trial Number IS RCT N74883561 . FINDINGS Six patients ( two [ open ] , four [ laparoscopic ] ) had no surgery , and 23 had missing surgical data ( nine , 14 ) . 253 and 484 patients actually received open and laparoscopic-assisted treatment , respectively . 143 ( 29 % ) patients underwent conversion from laparoscopic to open surgery . Proportion of Dukes ' C2 tumours did not differ between treatments ( 18 [ 7 % ] patients , open vs 34 [ 6 % ] , laparoscopic ; difference -0.3 % , 95 % CI -3.9 to 3.4 % , p=0.89 ) , and neither did in-hospital mortality ( 13 [ 5 % ] vs 21 [ 4 % ] ; -0.9 % , -3.9 to 2.2 % , p=0.57 ) . Apart from patients undergoing laparoscopic anterior resection for rectal cancer , rates of positive resection margins were similar between treatment groups . Patients with converted treatment had raised complication rates . INTERPRETATION Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes . However , impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use |
1,693 | 27,503,364 | The current study indicated grapefruit juice‐drug interaction varies substantially based on patient characteristics and /or grapefruit juice product‐related factors , including the amount of furanocoumarin constituents present in the juice | Abstract The objectives of this study were to investigate the effect of grapefruit juice low in furanocoumarins on CYP3A activity and to summarize previous findings of enzyme inhibition measured by the metabolism of midazolam after intake of grapefruit juice . | Milk thistle ( Silybum marianum ) extracts are widely used as a complementary and alternative treatment of various hepatic conditions and a host of other diseases/disorders . The active constituents of milk thistle supplements are believed to be the flavonolignans contained within the extracts . In vitro studies have suggested that some milk thistle components may significantly inhibit specific cytochrome P450 ( P450 ) enzymes . However , determining the potential for clinical ly significant drug interactions with milk thistle products has been complicated by inconsistencies between in vitro and in vivo study results . The aim of the present study was to determine the effect of a st and ardized milk thistle supplement on major P450 drug-metabolizing enzymes after a 14-day exposure period . CYP1A2 , CYP2C9 , CYP2D6 , and CYP3A4/5 activities were measured by simultaneously administering the four probe drugs , caffeine , tolbutamide , dextromethorphan , and midazolam , to nine healthy volunteers before and after exposure to a st and ardized milk thistle extract given thrice daily for 14 days . The three most abundant falvonolignans found in plasma , following exposure to milk thistle extracts , were silybin A , silybin B , and isosilybin B. The concentrations of these three major constituents were individually measured in study subjects as potential perpetrators . The peak concentrations and areas under the time-concentration curves of the four probe drugs were determined with the milk thistle administration . Exposure to milk thistle extract produced no significant influence on CYP1A2 , CYP2C9 , CYP2D6 , or CYP3A4/5 activities Objectives : Since grapefruit juice ( Gra ) inhibits hepatic P450 ( CYP3A4 ) , we studied its potential to enhance the effects of midazolam ( Mid ) and triazolam ( Trz ) , which are metabolized by the CYP3A4 isoenzyme . Methods : In Study I parallel groups of healthy students were given orally Mid 10 mg with water or grapefruit juice ( GraMid ) , two placebo groups receiving water or Gra . The effects of Mid were measured by psychomotor tests and by self-rating on visual analogue scales before and 30 and 90 min after intake . Study II was similar , but the post-treatment tests were at 45 and 90 min , and the active drugs used were 0.250 mg Trz , GraTrz , and Mid 10 mg . In the crossover Study III , 6 subjects took Mid 10 mg alone and with Gra ( GraMid ) and 750 mg erythromycin ( EryMid ) . Performance tests were made and blood was sample d before and 30 , 60 and 90 min after intake . Midazolam and its active metabolite α-OH-midazolam were assayed by gas chromatography ( GC ) and radioreceptor assay ( RRA ) . Results : In Study I , both Mid and GraMid impaired digit symbol substitution ( DSS ) , letter cancellation ( LC ) and flicker fusion ( CFF ) at 90 min . GraMid had more effect ( P < 0.05 ) than Mid on the DSS performance . Mid caused drowsiness at 30 and 90 min . Both Mid and GraMid caused clumsiness and a feeling of impaired performance at 90 min . In Study II , the active drugs impaired objective test performances ( DSS , LC , CFF ) at 90 min , without having a clear subjective effect . In Study III , Mid , EryMid and GraMid impaired performance in the DSS , LC and CFF tests . EryMid proved stronger than Mid and GraMid on DSS and LC tests at 30 min . Mean values of plasma midazolam ( and α-OH-midazolam ) at 30 , 60 , 90 and 120 min after Mid 10 mg were 68 ( 19 ) , 61 ( 19 ) , 43 ( 14 ) and 42 ( 12 ) μg⋅l−1 . The corresponding values after EryMid were 164 ( 14 ) , 137 ( 13 ) , 104(10 ) and 89(10 ) μg ⋅l−1 , and after GraMid 60 ( 12 ) , 69 ( 16 ) , 61 ( 15 ) and 57 ( 14 ) μg⋅l−1 . Conclusions : The grapefruit juice used did have any particular interaction with oral doses of 10 mg midazolam and 0.25 mg triazolam in healthy young subjects BACKGROUND Grapefruit juice ( GFJ ) enhances the systemic exposure of numerous CYP3A4 drug substrates , including felodipine , by inhibiting intestinal ( but not hepatic ) first-pass metabolism . Furanocoumarins have been identified as major CYP3A4 inhibitors contained in the juice , but their contribution to the GFJ effect in vivo remains unclear . OBJECTIVE To ascertain whether furanocoumarins mediate the GFJ-felodipine interaction , a furanocoumarin-free GFJ was created and tested against orange juice and the original GFJ with respect to the oral pharmacokinetics of felodipine . DESIGN With the use of food- grade solvents and absorption resins , furanocoumarins were removed ( approximately 99 % ) from whole GFJ , whereas other major ingredients ( flavonoids ) were retained . In an open , 3-way , r and omized crossover design , 18 healthy volunteers ingested felodipine ( 10 mg ) with 1 of the 3 juices ( 240 mL ) . Blood was collected over 24 h. At least 1 wk elapsed between juice treatments . RESULTS The median and range of the area under the curve and the maximum concentration of felodipine were significantly ( P < 0.001 ) greater with consumption of GFJ [ 110 ( range : 58 - 270 ) nmol . h/L and 21 ( 7.6 - 50 ) nmol/L , respectively ] than with that of orange juice [ 54 ( 29 - 150 ) nmol . h/L and 7.6 ( 3.4 - 13.9 ) nmol/L , respectively ] or furanocoumarin-free GFJ [ 48 ( 23 - 120 ) nmol . h/L and 8.3 ( 3.0 - 16.6 ) nmol/L , respectively ] . GFJ , orange juice , and furanocoumarin-free GFJ did not differ significantly ( P > 0.09 ) in median time to reach maximum plasma concentration [ 2.5 ( 1.5 - 6 ) , 2.8 ( 1.5 - 4 ) , and 2.5 ( 2 - 6 ) h , respectively ] or terminal half-life [ 6.6 ( 4.2 - 13.6 ) , 7.8 ( 4.4 - 13.2 ) , and 6.8 ( 2.6 - 14.4 ) h , respectively ] . CONCLUSION Furanocoumarins are the active ingredients in GFJ responsible for enhancing the systemic exposure of felodipine and probably other CYP3A4 substrates that undergo extensive intestinal first-pass metabolism Systemic clearance of intravenous ( IV ) alfentanil ( ALF ) is an in vivo probe for hepatic cytochrome P450 ( CYP ) 3A activity , miosis is a surrogate for plasma ALF concentrations , and IV ALF miosis is a noninvasive probe for hepatic CYP3A . This investigation characterized the bioavailability and first‐pass metabolism of oral ALF and tested the hypotheses that ( 1 ) first‐pass ALF clearance reflects first‐pass CYP3A activity , ( 2 ) miosis after oral ALF will reflect intestinal and hepatic CYP3A activity , and ( 3 ) miosis can approximate plasma concentration‐based pharmacokinetic measures for IV and oral ALF as a noninvasive in vivo probe for hepatic and first‐pass CYP3A activity and drug interactions . Results were compared with those for midazolam ( MDZ ) , an alternative CYP3A probe Consumption of typical quantities of grapefruit juice ( GFJ ) increases the oral bioavailability of several CYP3A4 substrates without affecting their elimination , consistent with selective inhibition of intestinal but not hepatic CYP3A4 . However , increases in the AUCs of CYP3A4 substrates recently associated with the consumption of large amounts of GFJ were similar to those observed with potent inhibitors of hepatic CYP3A4 . The current study compared the effects of consuming large quantities and more typical amounts of GFJ on the activity of hepatic and intestinal cytochrome P450 3A4 in vivo , employing the erythromycin breath test ( EBT ) and oral midazolam pharmacokinetics . This was a two-phase , r and omized , placebo-controlled crossover study , with each phase conducted with a separate panel of subjects . In Phase I , 8 male volunteers were r and omized to the order of receiving one glass ( 240 mL ) of water ( placebo ) or double-strength ( DS ) GFJ tid for 2 days and then 90 , 60 , and 30 minutes prior to administration of probe drugs on the 3rd day . In Phase II , 16 male volunteers were r and omized to the order of receiving one glass of ( 1 ) single-strength ( SS ) GFJ , ( 2 ) DS GFJ , and ( 3 ) water ( placebo ) . All treatments were administered in a fasted state . There was at least a 7-day washout period between treatments . Probe drugs , administered 30 minutes or 1 hour following each treatment in Phase I or II , respectively , consisted of oral midazolam ( 2 mg ) coadministered with IV [ 14 G N-methyl ] erythromycin ( 0.03 mg ) . The EBT was performed 20 minutes following erythromycin administration . Blood was collected during the 24 hours following probe drug administration for the analysis of midazolam pharmacokinetics . In Phase I , consumption of one glass of DS GFJ tid for 3 days increased the Cmax of midazolam 3-fold , the AUC 6-fold , and the t1/2 2-fold and decreased the amount of exhaled 14CO2 in all 8 subjects , with a mean decrease in EBT of 18 % . In Phase II , consumption of one glass of DS GFJ significantly increased the AUC and Cmax of midazolam approximately 2-fold without a significant effect on the t1/2 of midazolam or the EBT . The effects of consuming one glass of SS GFJ on midazolam pharmacokinetics and the EBT were not significantly different from those of one glass of DS GFJ . It was concluded that consumption of one glass of DS GFJ tid for 3 days significantly increased the AUC , Cmax , and t1/2 of midazolam and reduced EBT values , reflecting inhibition of both hepatic and intestinal CYP3A4 . In contrast , consumption of one glass of SS or DS GFJ increased midazolam AUC and Cmax , with little effect on the midazolam t1/2 and EBT values , reflecting preferential inhibition of intestinal CYP3A4 . Alterations of midazolam AUC and Cmax induced by nine glasses of DS GFJ were significantly greater than those produced by one glass of SS or DS GFJ . These data suggest that GFJ inhibits intestinal and hepatic CYP3A4 in an exposure-dependent fashion and that patients taking medications that are CYP3A4 substrates are at risk for developing drug-related adverse events if they consume large amounts of grapefruit juice To evaluate the effect of regular‐strength grapefruit juice , a cytochrome P4503A4 ( CYP3A4 ) inhibitor , on the pharmacokinetics of a commonly prescribed regimen of oral lovastatin Grapefruit juice produces a marked and variable increase in felodipine bioavailability . The pharmacokinetics of felodipine and its single primary oxidative metabolite , dehydrofelodipine , were studied after drug administration with 200 ml water , grapefruit juice , or naringin in water at the same concentration as the juice in a r and omized crossover trial of nine healthy men . With grapefruit juice , mean ± SEM felodipine area under the plasma concentration‐time curve ( AUC ) and peak plasma concentration ( Cmax ) were 206 % ± 23 % ( range , 123 % to 330 % , p < 0.01 ) and 170 % ± 24 % ( range , 127 % to 310 % , p < 0.02 ) , respectively , compared with water . Dehydrofelodipine/felodipine ratios for AUC ( 1.5 ± 0.2 versus 2.2 ± 0.2 , p < 0.001 ) and felodipine Cmax ( 1.5 ± 0.2 versus 2.2 ± 0.2 , p < 0.001 ) were reduced , consistent with inhibition of presystemic felodipine metabolism . Intersubject changes in felodipine and dehydrofelodipine AUC supported inhibition of both primary and secondary metabolic steps as a mechanism . The interaction could not be predicted from baseline pharmacokinetics with water and did not result in more consistent bioavailability among individuals . Naringin solution produced much less of an interaction , showing that other factors were important A citrus breeding program aim ed at developing low furanocoumarin ( FC ) grapefruit cultivars provided 40 grapefruit juice ( GFJ ) sample s containing variable concentrations of FC derivatives , established as being mechanism-based ( irreversible ) inhibitors of human CYP3A isoforms . The principal inhibitory FCs were identified as 6′,7′-dihydroxybergamottin , along with a series of dimeric compounds ( spiroesters ) having high inhibitory potency . A r and om subset of the GFJ sample s ( n = 25 ) were tested as CYP3A inhibitors using an in vitro model based on human liver microsomal metabolism of the index substrate triazolam . The reciprocal values of in vitro 50 % inhibitory concentrations ( IC50 ) were highly correlated with concentrations of inhibitory FCs in the GFJ sample s ( r2 = 0.96 ) . However the correlations were driven mainly by a few sample s having high FC content and high reciprocal IC50 ( corresponding to low IC50 ) . Among the rest of the sample s , the relationship was less robust . Further study is needed to determine how low the FC content needs to be ( or how high the IC50 needs to be ) to assure minimal risk of clinical interactions involving GFJ and CYP3A substrate drugs Recently , a new type of interaction has been reported in which fruit juices diminish oral drug bioavailability through inhibition of organic anion-transporting polypeptide ( OATP ) . In this study , we aim ed to clarify the duration of OATP inhibition by grapefruit juice ( GFJ ) , and to compare it with the duration of GFJ-induced inhibition of cytochrome P450 ( CYP ) 3A4 activity . Seven healthy volunteers were enrolled in this open-label , single-sequence study . They were orally administered celiprolol ( 100 mg ) and midazolam ( 15 µg/kg ) with water on the control day . Three days later , they ingested GFJ ( 200 mL ) 3 times a day for 3 d. On day 1 , the same drugs were administered with GFJ . On days 3 and 7 , the same drugs were administered with water . Pharmacokinetics of both drugs were evaluated on each trial day . The peak plasma concentration ( Cmax ) and the area under the plasma concentration-time curve from 0 to 8 h ( AUC0 - 8 ) of celiprolol significantly decreased on day 1 , and the mean ratios of these values and the corresponding control-day values were 0.18 and 0.25 , respectively . The Cmax and AUC0 - 8 returned to the control levels on days 3 and 7 . In contrast , AUC0 - 8 of midazolam were higher on days 1 and 3 than on the control day ( mean ratio , 2.12 and 1.47 , respectively ) . The AUC0 - 8 returned to the control level on day 7 . In conclusion , results of this study indicated that the OATP inhibition caused by GFJ dissipated faster than GFJ-mediated alterations in CYP3A4 activity , which were sustained for at least 48 Purpose The drug label of sunitinib includes a warning for concomitant use of grapefruit juice ( GJ ) but clinical evidence for this drug interaction is lacking . The aim of this study is to determine the effect of GJ , a potent intestinal cytochrome P450 ( CYP ) 3A4 inhibitor , on steady-state sunitinib pharmacokinetics ( PK ) . Methods Sunitinib PK was evaluated in eight cancer patients receiving sunitinib monotherapy in a “ 4 weeks on—2 weeks off ” dose regimen . Serial blood sample s for PK analysis of sunitinib were collected on two separate days . On both PK days , patients received a single oral dose of 7.5-mg midazolam as a phenotypic probe for assessment of intestinal CYP3A4 activity . The first PK day was at steady-state sunitinib PK ( between days 14–20 ) , the second PK day was on day 28 . On days 25 , 26 and 27 , 200-mL GJ was consumed 3 times a day . The effect of GJ on sunitinib exposure was assessed by comparing sunitinib PK with and without GJ . Results Concomitant use of GJ and sunitinib result ed in an 11 % increase of the relative bioavailability of sunitinib ( P < 0.05 ) . The effect of GJ on CYP3A4 activity was confirmed by an increase of ~50 % of mean midazolam exposure ( AUC0–24 h ) from 122.1 to 182.0 ng h/mL ( P = 0.034 ) . Conclusion GJ consumption results in a marginal increase in sunitinib exposure which is not considered clinical ly relevant . There is no clinical evidence underscoring the warning in the sunitinib drug label regarding concomitant use of GJ The acute hemodynamic and pharmacokinetic interactions between the vasodilating/diuretic drugs ethanol and felodipine , a 1,4-dihydropyridine calcium entry blocker , were assessed in 10 patients with untreated borderline hypertension . A non-intoxicating dose of ethanol or placebo was administered in a r and omized , crossover , double-blind manner followed by felodipine 5 mg . Maximum hemodynamic effects occurred at four hours . Felodipine plus ethanol decreased mean ( + /- SE ) supine total peripheral resistance ( 13 + /- 2 vs 17 + /- 2 mmHg/L/min , p = 0.05 ) and diastolic blood pressure ( 68 + /- 3 vs 75 + /- 2 mmHg , p less than 0.05 ) associated with increased heart rate ( 72 + /- 3 vs 67 + /- 2 bpm , p less than 0.05 ) and cardiac index ( 3.7 + /- 0.4 vs 3.0 + /- 0.3 L/min/m2 , p less than 0.05 ) more than felodipine alone . Greater differences were apparent in st and ing blood pressure . Co-administration of ethanol decreased st and ing systolic ( 113 + /- 8 vs 126 + /- 5 mmHg , p less than 0.01 ) and diastolic ( 69 + /- 5 vs 82 + /- 3 mmHg , p less than 0.01 ) blood pressure to a greater degree , but heart rate was not altered ( 87 + /- 6 vs 84 + /- 3 bpm ) . Substantial four hour diuresis occurred with both treatments ( 807 + /- 126 vs 806 + /- 169 ml ) . Adverse effects were frequent but most often occurred with felodipine plus ethanol ( 17 vs 11 ) as a result of postural lightheadedness ( 5 vs 1 ) related to hypotension . Felodipine bioavailability was not influenced by ethanol . However felodipine plasma concentrations greatly exceeded the expected concentrations , possibly due to a pharmacokinetic interaction with the grapefruit juice vehicle . Ethanol can enhance felodipine hemodynamics to produce clinical ly relevant adverse effects The bioavailability of some dihydropyridine calcium antagonists can be markedly augmented by grapefruit juice and may involve the bioflavonoid naringin . The pharmacokinetics of nisoldipine coat‐core tablet were studied in a Latin square– design ed trial in which 12 healthy men were administered the drug with water , grapefruit juice , or encapsulated naringin powder at the same amount as that assayed in the juice . Compared with water , grapefruit juice increased the maximum concentration of nisoldipine to 406 % ± 73 % ( mean ± SEM ; range , 107 % to 836 % ; p < 0.001 ) , increased the area under the plasma concentration‐time curve to 198 % ± 46 % ( range , 81 % to 682 % ; p < 0.001 ) , and reduced time to reach maximum nisoldipine concentration to 58 % ± 9 % ( range , 13 % to 100 % ; p < 0.01 ) , probably by inhibition of presystemic metabolism and possibly by enhancement of drug dissolution . The interaction could not be predicted from baseline pharmacokinetics with water and result ed in greater interindividual variability . The naringin capsule did not change nisoldipine pharmacokinetics . All treatments produced minor effects on supine blood pressure and heart rate , probably because subjects were normotensive . Current information supports the caution ing of patients about concomitant ingestion of grapefruit juice and nisoldipine Components of grapefruit juice may impair the activity of intestinal cytochrome P450 ( CYP ) 3A enzymes , sometimes result ing in clinical ly important drug interactions . The time course of recovery from CYP3A inhibition after a single exposure to grapefruit juice is not clearly established To investigate the effects of grapefruit juice on the pharmacokinetics and dynamics of midazolam |
1,694 | 27,288,517 | Exercise therapy provided high evidence of being as effective as surgery intervention and better than no treatment or placebo treatment to improve pain , function and range of motion in the short , mid and long terms .
The combination of mobilisation and exercises provided high evidence to decrease pain and improve function in the short term .
There is limited evidence for improvements on the outcomes with the isolated application of manual therapy .
High level of evidence was synthesis ed regarding the lack of beneficial effects of physical re sources such as low-level laser , ultrasound and pulsed electromagnetic field ( PEMF ) on pain , function or range of motion in the treatment of SAPS .
There is limited evidence for microwave diathermy and transcutaneous electrical nerve stimulation .
There is moderate evidence to no benefits with taping in the short term .
Effects of diacutaneous fibrolysis and acupuncture are not well established yet .
Exercise therapy should be the first-line treatment to improve pain , function and range of motion .
The addition of mobilisations to exercises may accelerate reduction of pain in the short term . | AIM To summarise the current evidence regarding the effectiveness of physical therapy on pain , function and range of motion in individuals with subacromial pain syndrome ( SAPS ) . | Background and purpose A programme based on eccentric exercises for treating subacromial pain was in a previous study found effective at 3-month follow-up . The purpose s of the present study were to investigate whether the results were maintained after 1 year and whether the baseline Constant-Murley score , rotator cuff status and radiological findings influenced the outcome . Patients and methods 97 patients on the waiting list for arthroscopic subacromial decompression had been r and omised to a specific exercise programme or unspecific exercises ( controls ) . After 3 months of exercises , the patients were asked whether they still wanted surgery and this option was available until a 1-year follow-up . 1 year after inclusion or 1 year after surgery , the number of patients who decided to have surgery in each group was compared . The choice of surgery was related to the baseline Constant-Murley score , ultrasound and radiographs taken at inclusion . Results All patients had improved significantly ( p<0.0001 ) in the Constant-Murley score at the 1-year follow-up . Significantly more patients in the control group decided to have surgery ( 63 % ) than those in the specific exercise group ( 24 % ; p<0.0001 ) . Patients who decided to have surgery had a significantly lower baseline Constant-Murley score and more often a full-thickness tear . Patients with partial tears did not differ from those with intact tendons . Interpretation The positive short-term results of specific exercises were maintained after 1 year , and this exercise strategy reduces the need for surgery . Full-thickness tear and a low baseline Constant-Murley score appear to be a predictive marker for a less good outcome . Trial registration number Clinical trials NCT01037673 STUDY DESIGN A prospect i ve r and omized clinical trial . OBJECTIVE To compare the effectiveness of 2 physical therapy treatment approaches for impingement syndrome of the shoulder . BACKGROUND Manual physical therapy combined with exercise is a commonly applied but currently unproven clinical treatment for impingement syndrome of the shoulder . METHODS AND MEASURES Thirty men and 22 women ( age 43 years + /- 9.1 ) diagnosed with shoulder impingement syndrome were r and omly assigned to 1 of 2 treatment groups . The exercise group performed supervised flexibility and strengthening exercises . The manual therapy group performed the same program and received manual physical therapy treatment . Both groups received the selected intervention 6 times over a 3-week period . The testers , who were blinded to group assignment , measured strength , pain , and function before treatment and after 6 physical therapy visits . Strength was a composite score of isometric strength tests for internal rotation , external rotation , and abduction . Pain was a composite score of visual analog scale measures during resisted break tests , active abduction , and functional activities . Function was measured with a functional assessment question naire . The visual analog scale used to measure pain with functional activities and the functional assessment question naire were also measured 2 months after the initiation of treatment . RESULTS Subjects in both groups experienced significant decreases in pain and increases in function , but there was significantly more improvement in the manual therapy group compared to the exercise group . For example , pain in the manual therapy group was reduced from a pretreatment mean ( + /- SD ) of 575.8 ( + /- 220.0 ) to a posttreatment mean of 174.4 ( + /- 183.1 ) . In contrast , pain in the exercise group was reduced from a pretreatment mean of 557.1 ( + /- 237.2 ) to a posttreatment mean of 360.6 ( + /- 272.3 ) . Strength in the manual therapy group improved significantly while strength in the exercise group did not . CONCLUSION Manual physical therapy applied by experienced physical therapists combined with supervised exercise in a brief clinical trial is better than exercise alone for increasing strength , decreasing pain , and improving function in patients with shoulder impingement syndrome Evidence -based practice involves the use of evidence from systematic review s and r and omised controlled trials , but the extent of this evidence in physiotherapy has not previously been surveyed . The aim of this survey is to describe the quantity and quality of r and omised controlled trials and the quantity of systematic review s relevant to physiotherapy . The Physiotherapy Evidence Data base ( PEDro ) was search ed . The quality of trials was assessed with the PEDro scale . The search identified a total of 2,376 r and omised controlled trials and 332 systematic review s. The first trial was published in 1955 and the first review was published in 1982 . Since that time , the number of trials and review s has grown exponentially . The mean PEDro quality score has increased from 2.8 in trials published between 1955 and 1959 to 5.0 for trials published between 1995 and 1999 . There is a substantial body of evidence about the effects of physiotherapy . However , there remains scope for improvements in the quality of the conduct and reporting of clinical trials OBJECTIVES : Conflicting results were reported about the effectiveness of Low level laser therapy on musculoskeletal disorders . The aim of this study was to investigate the effectiveness of 850‐nm gallium arsenide aluminum ( Ga‐As‐Al ) laser therapy on pain , range of motion and disability in subacromial impingement syndrome . METHODS : A total of 52 patients ( 33 females and 19 males with a mean age of 53.59±11.34 years ) with subacromial impingement syndrome were included . The patients were r and omly assigned into two groups . Group I ( n = 30 , laser group ) received laser therapy ( 5 joule/cm2 at each point over maximum 5‐6 painful points for 1 minute ) . Group II ( n = 22 , placebo laser group ) received placebo laser therapy . Initially cold pack ( 10 minutes ) was applied to all of the patients . Also patients were given an exercise program including range of motion , stretching and progressive resistive exercises . The therapy program was applied 5 times a week for 14 sessions . Pain severity was assessed by using visual analogue scale . Range of motion was measured by goniometer . Disability was evaluated by using Shoulder Pain and Disability Index . RESULTS : In group I , statistically significant improvements in pain severity , range of motion except internal and external rotation and SPADI scores were observed compared to baseline scores after the therapy ( p<0.05 ) . In Group II , all parameters except range of motion of external rotation were improved ( p<0.05 ) . However , no significant differences were recorded between the groups ( p>0.05 ) . CONCLUSIONS : The Low level laser therapy seems to have no superiority over placebo laser therapy in reducing pain severity , range of motion and functional disability Background : Repetitive or sustained elevated shoulder postures have been identified as a significant risk factor for occupationally related shoulder musculoskeletal disorders . Construction workers exposed to routine overhead work have high rates of shoulder pain that frequently progresses to functional loss and disability . Exercise interventions have potential for slowing this progression . Aims : To evaluate a therapeutic exercise programme intended to reduce pain and improve shoulder function . Methods : Construction worker volunteers were screened by history and clinical examination to test for inclusion /exclusion criteria consistent with shoulder pain and impingement syndrome . Sixty seven male symptomatic workers ( mean age 49 ) were r and omised into a treatment intervention group ( n = 34 ) and a control group ( n = 33 ) ; asymptomatic subjects ( n = 25 ) participated as an additional control group . Subjects in the intervention group were instructed in a st and ardised eight week home exercise programme of five shoulder stretching and strengthening exercises . Subjects in the control groups received no intervention . Subjects returned after 8–12 weeks for follow up testing . Results : The intervention group showed significantly greater improvements in the Shoulder Rating Question naire ( SRQ ) score and shoulder satisfaction score than the control groups . Average post-test SRQ scores for the exercise group remained below levels for asymptomatic workers . Intervention subjects also reported significantly greater reductions in pain and disability than controls . Conclusions : Results suggest a home exercise programme can be effective in reducing symptoms and improving function in construction workers with shoulder pain Objective To investigate the efficacy of a programme of manual therapy and exercise treatment compared with placebo treatment delivered by physiotherapists for people with chronic rotator cuff disease . Design R and omised , participant and single assessor blinded , placebo controlled trial . Setting Metropolitan region of Melbourne , Victoria , Australia . Participants 120 participants with chronic ( > 3 months ) rotator cuff disease recruited through medical practitioners and from the community . Interventions The active treatment comprised a manual therapy and home exercise programme ; the placebo treatment comprised inactive ultrasound therapy and application of an inert gel . Participants in both groups received 10 sessions of individual st and ardised treatment over 10 weeks . For the following 12 weeks , the active group continued the home exercise programme and the placebo group received no treatment . Main outcome measures The primary outcomes were pain and function measured by the shoulder pain and disability index , average pain on movement measured on an 11 point numerical rating scale , and participants ’ perceived global rating of overall change . Results 112 ( 93 % ) participants completed the 22 week trial . At 11 weeks no difference was found between groups for change in shoulder pain and disability index ( 3.6 , 95 % confidence interval −2.1 to 9.4 ) or change in pain ( 0.7 , −0.1 to 1.5 ) ; both groups showed significant improvements . More participants in the active group reported a successful outcome ( defined as “ much better ” ) , although the difference was not statistically significant : 42 % ( 24/57 ) of active participants and 30 % ( 18/61 ) of placebo participants ( relative risk 1.43 , 0.87 to 2.34 ) . The active group showed a significantly greater improvement in shoulder pain and disability index than did the placebo group at 22 weeks ( between group difference 7.1 , 0.3 to 13.9 ) , although no significant difference existed between groups for change in pain ( 0.9 , −0.03 to 1.7 ) or for the percentage of participants reporting a successful treatment outcome ( relative risk 1.39 , 0.94 to 2.03 ) . Several secondary outcomes favoured the active group , including shoulder pain and disability index function score , muscle strength , interference with activity , and quality of life . Conclusion A st and ardised programme of manual therapy and home exercise did not confer additional immediate benefits for pain and function compared with a realistic placebo treatment that controlled for therapists ’ contact in middle aged to older adults with chronic rotator cuff disease . However , greater improvements were apparent at follow-up , particularly in shoulder function and strength , suggesting that benefits with active treatment take longer to manifest . Trial registration Clinical trials NCT00415441 OBJECTIVE The aim of this study was to determine the effectiveness of Kinesio taping ( KT ) application added to the exercise treatment of subacromial impingement syndrome ( SIS ) . METHODS Thirty-eight ( 25 female , 13 male ) patients with SIS were r and omly divided into therapeutic KT ( n=19 ) and sham KT ( n=19 ) groups . All patients received the same exercise therapy in addition to therapeutic or sham KT at 3-day intervals for 12 days . The groups were compared according to pain , range of motion ( ROM ) , muscle strength and DASH and Constant scores before treatment and at the 5th and 12th treatment days . RESULTS Within group comparisons showed significant improvements in both groups at the 5th and 12th day evaluations ( p<0.05 ) . In comparisons between the groups , pain with movement and DASH scores in the therapeutic group were significantly lower at the 5th day ( p<0.01 ) . There were significant improvements in night pain , pain with movement , DASH score , shoulder external rotation muscle strength , and pain free shoulder abduction ROM in the therapeutic group at the 12th day ( p<0.05 ) . Passive shoulder flexion ROM increased more in the sham group at the 12th day ( p<0.05 ) . CONCLUSION The addition of KT application to the exercise program appears to be more effective than the exercise program alone for the treatment of SIS Background The physiotherapy dynamic humeral centring ( DHC ) aims to prevent subacromial impingement of rotator cuff tendons during elevation of the arm . The objective of the study was to determine whether DHC acts via an effect on subacromial impingement mechanism by assessing its effect on painful elevation of the arm in subacromial impingement syndrome . Methods This is a secondary analysis of results of a r and omised controlled trial of the effectiveness of DHC . Sixty-nine patients with subacromial impingement syndrome were prospect ively included . Patients and the assessor were blinded to the study hypothesis and treatment , respectively . Patients underwent DHC or non-specific mobilisation as a control for 6 weeks in 15 supervised individual outpatient sessions with home exercises . Outcomes were pain-free range of motion and presence of painful arc of the shoulder , both in active flexion and abduction of the arm at 3 months . Results At 3 months , pain-free range of motion , both flexion and abduction , was greater in the DHC group than in the mobilisation group . The number of patients with painful arc during flexion was decreased in the DHC group . Conclusions DHC improves painful active elevation of the arm . We suggest that DHC may act via a specific effect on subacromial impingement mechanism BACKGROUND AND PURPOSE Exercise therapy is a commonly used conservative therapy for long-term subacromial pain . However , there is no consensus regarding what type of exercises and dosage is most effective . The aim of this study was to compare the effect of two exercise programmes : 1 ) high-dosage ( HD ) medical exercise therapy versus 2 ) low-dosage ( LD ) exercise therapy programme for subjects with long-term subacromial pain . METHODS This study used a r and omized , controlled clinical trial with an intention-to-treat analysis . Sixty-one subjects were r and omly assigned by concealment either to an HD medical exercise therapy group ( n = 31 ) or to an LD exercise therapy group ( n = 30 ) . Pain ( visual analogue scale [ VAS ] ) and function ( Shoulder Rating Question naire [ SRQ ] ) were measured at inclusion , at end of treatment and at 6 and 12 months follow-up . RESULTS There were no differences between groups at inclusion ( baseline ) regarding any variables . During the three months treatment period , five subjects ( 8 % ) dropped out , and another seven ( 11 % ) dropped out at one-year follow-up . At the end of treatment , both pain and function had improved significantly in favour of the HD therapy , between-group differences in VAS were -2.7 ( -3.9 to 0.9 ) , and for activity limitations , the between-group differences in the SRQ increased by 24.5 points ( 14.5 - 35.7 ) . The differences between groups were both statistically and clinical ly significant at 6 and 12 months follow-up . CONCLUSION In subjects with long-term subacromial pain syndrome , HD medical exercise therapy is superior to a conventional LD exercise programme . For clinicians to obtain similar positive results with HD medical exercise therapy , factors such as good communication skills , constant close personal supervision during exercise treatment and having from three to five subjects in a group setting are important Context The shoulder impingement syndrome includes conditions , such as rotator cuff tendinosis and shoulder bursitis . Conservative management may include corticosteroid injections ( CSIs ) or manual physical therapy ( MPT ) . Contribution In this r and omized , controlled trial , groups of patients with the shoulder impingement syndrome receiving CSI or MPT showed similar symptom improvements that did not differ significantly . Compared with the MPT group , the CSI group used more health care re sources during the 1-year follow-up . Caution The trial recruited only patients referred to MPT . Implication Manual physical therapy and CSI produced similar clinical outcomes in patients with the shoulder impingement syndrome . The Editors The shoulder impingement syndrome ( SIS ) is a generic term used for patients with shoulder pain that encompasses the rotator cuff syndrome , tendinosis of the rotator cuff muscles , and bursitis in the shoulder area ( 1 ) . It has a cumulative incidence between 5 and 30 per 1000 person-years ( 2 , 3 ) . Conservative treatment options include corticosteroid injections ( CSIs ) and physical therapy . Subacromial CSI is one of the most common procedures used by orthopedists , rheumatologists , and general practitioners ( 4 , 5 ) . However , evidence to support long-term efficacy is conflicting ( 610 ) . Clinical practice guidelines can not recommend for or against CSI for rotator cuff pathology without evidence of tears ( 11 ) . Four recent systematic review s have differing conclusions on the efficacy of CSI for SIS ( 6 , 8 , 9 , 12 ) , but the consensus suggests that any benefit may only be short-term . Although manual physical therapy ( MPT ) may be effective for SIS management ( 1321 ) , 2 recent systematic review s found no clear evidence to suggest additional benefits of MPT to other interventions ( 22 , 23 ) , indicating the need for further research . Data are also lacking about the patterns and timing of CSI and MPT use for patients with SIS . Studies suggest that a CSI is often considered initially ( 4 , 5 ) , whereas a referral to physical therapy may occur only 24 % of the time ( 24 ) . Other studies introduced CSI only after 6 weeks of physical therapy was unsuccessful ( 5 ) . Some investigations evaluated the effect of providing CSI before , or in conjunction with , MPT or shoulder exercises ( 14 , 25 , 26 ) , but CSI and MPT have not been directly compared . The objective of this study was to compare the 1-year effectiveness of CSI and MPT for SIS management . Methods Design Overview This pragmatic , r and omized , controlled trial compared 2 treatments for patients with SIS : subacromial CSI and MPT . The primary end point was 1-year improvement on the Shoulder Pain and Disability Index ( SPADI ) . Secondary outcomes included changes in Global Rating of Change ( GRC ) scale and Numeric Pain Rating Scale ( NPRS ) scores and shoulder-related health care use . We followed the SPIRIT ( St and ard Protocol Items : Recommendations for Interventional Trials ) statement at the time of protocol development ( 27 ) , and our reporting followed the CONSORT ( Consoli date d St and ards of Reporting Trials ) extension for pragmatic clinical trials ( 28 ) . The study was approved by the Madigan Army Medical Center Institutional Review Board , the trial was registered ( Clinical Trials.gov : NCT01190891 ) , and the protocol was published with open access ( 29 ) . Setting and Participants Consecutive patients aged 18 to 65 years with a primary symptom of unilateral shoulder pain referred from family practice and orthopedic clinics to the physical therapy department at Madigan Army Medical Center were screened for eligibility during their initial visit in the physical therapy clinic . Exclusion criteria included a history of shoulder dislocation , fracture , or adhesive capsulitis ; history of CSI or physical therapy for the shoulder pain in the past 3 months ; baseline SPADI score less than 20 % ; reproduction of shoulder symptoms with cervical spine examination ; history of systemic or neurologic disease affecting the shoulder ; positive rotator cuff lag sign or history of full-thickness rotator cuff tear ; pending litigation ; or inability to attend physical therapy for 3 consecutive weeks . Patients at this medical center included a mix of active-duty and retired military service members and their families . Copayments were not required for care . R and omization and Interventions The r and omization schedule was computer-generated , with assignments placed in opaque , sequentially numbered envelopes by an off-site investigator not involved with patient care or follow-up . Treatment allocation was revealed after collection of baseline outcomes . Patients and treating clinicians were not blind to the intervention . The research assistant who collected outcome assessment s at each time point was blind to group assignment . Two physical therapists provided the MPT , and 1 physician administered all of the injections . Patients were allowed to continue any current medications prescribed by their primary care providers ( PCPs ) . MPT Group At the first session , the physical therapists performed a st and ardized clinical examination to identify relevant impairments ( weakness , mobility , or pain ) . The MPT intervention consisted of a combination of joint and soft-tissue mobilizations ; manual stretches ; contractrelax techniques ; and reinforcing exercises directed to the shoulder girdle or thoracic or cervical spine . Specific details of the treatment are published ( 29 ) . Patients did not receive identical treatments , but the MPT techniques were matched to individual impairments identified on examination . Patients were treated twice weekly over a 3-week period , a typical episode of care for SIS , by the same physical therapy in most cases . Home exercises were prescribed to reinforce clinic interventions ( 29 ) . The physical therapists were fellowship-trained in MPT from an American Physical Therapy Associationcredentialed program . CSI Group A credentialed family practice physician with sports medicine fellowship training injected 40 mg of triamcinolone acetonide to the subacromial space of the symptomatic shoulder ( 29 ) . Each participant received a h and out explaining the effects of the steroid injection and how to manage potential side effects . As many as 3 total injections could be administered by the study physician ( > 1 month apart ) during the 1-year period . Patients received printed instructions to perform a gentle gravity-assisted distraction and oscillatory pendulum exercise . Patients were discouraged , but not prohibited , from seeking additional care for at least the first month ( study -related treatment period ) . At the 1- , 3- , and 6-month follow-up periods , patients were also given written instructions and a number to call if they believed that they were not improving and needed additional care . A study coordinator , who was not involved with data collection or treatment , fielded these calls . She advised patients in the MPT group to return to their PCP for additional care and facilitated contact with the physician providing the injection for patients in the CSI group . Each case was managed individually , and another CSI was administered if the patient and physician mutually agreed that it was appropriate . Patients in either group could return to their PCP if they felt the need , and the PCP would manage the patient as they thought best , potentially including a CSI or referral to physical therapy . These patients would not see the same physical therapist or physician who administered the initial study intervention . Outcomes and Follow-up Outcome measurements were administered at baseline , 1 month , 3 months , 6 months , and 1 year . The SPADI is a 100-point , 13-item , self-administered question naire that is divided into 2 subscales : a 5-item pain subscale and an 8-item disability subscale . It is valid , is responsive to change , and accurately discriminates between improving and worsening status ( 30 , 31 ) . The minimal clinical ly important difference for the SPADI is a change between 8 and 13 points ( 6 % to 10 % ) ( 32 ) . The GRC is an instrument that measures overall perceived changes in the participant 's quality of life ( 33 ) . It provides a valid measurement of change in patients ' perceived status ( 34 ) . A GRC score of 3 rating points or greater is clinical ly meaningful ( 35 ) . An 11-point NPRS ranging from 0 ( no pain ) to 10 ( worst imaginable pain ) was used to assess pain intensity ( 36 ) . This scale has been demonstrated to be a reliable , generalizable , and internally consistent measure of clinical and experimental pain intensity ( 37 , 38 ) . The suggested minimal clinical ly important difference for the NPRS is a change of 2 points ( 39 ) . A research assistant blinded to treatment allocation collected health care use information from electronic health records at the 1-year follow-up using an established process ( 40 , 41 ) . This included additional use after completion of the study interventions . We identified shoulder-related visits to physical therapists , PCPs , rheumatologists , and orthopedists , as well as frequency and types of procedures , including additional steroid injections , magnetic resonance imaging , and radiography , similar to other studies ( 42 ) . A second clinician manually verified the electronic health record information to ensure that the care was related to the same shoulder condition . Statistical Analysis The sample size estimated to achieve 80 % power to detect a 12-point difference ( or a 9.2 % change ) in the SPADI , based on a reported minimal clinical ly important difference range of 8 to 13 points ( 32 ) , with an SD of 10 points , a 2-tailed test , and an level of 0.05 was 43 participants per group . To allow for a conservative withdrawal rate of approximately 20 % , we recruited 104 participants . The primary analyses of effectiveness included all available data from patients who received their assigned treatment ( that is , the CSI or at least 1 session of MPT ) . We used a linear mixed-effects model , which is flexible in accommodating data assumed to be missing at STUDY DESIGN Prospect i ve , r and omized , double-blinded , clinical trial using a repeated- measures design . OBJECTIVES To determine the short-term clinical efficacy of Kinesio Tape ( KT ) when applied to college students with shoulder pain , as compared to a sham tape application . BACKGROUND Tape is commonly used as an adjunct for treatment and prevention of musculoskeletal injuries . A majority of tape applications that are reported in the literature involve nonstretch tape . The KT method has gained significant popularity in recent years , but there is a paucity of evidence on its use . METHODS AND MEASURES Forty-two subjects clinical ly diagnosed with rotator cuff tendonitis/impingement were r and omly assigned to 1 of 2 groups : therapeutic KT group or sham KT group . Subjects wore the tape for 2 consecutive 3-day intervals . Self-reported pain and disability and pain-free active ranges of motion ( ROM ) were measured at multiple intervals to assess for differences between groups . RESULTS The therapeutic KT group showed immediate improvement in pain-free shoulder abduction ( mean + /- SD increase , 16.9 degrees + /- 23.2 degrees ; P = .005 ) after tape application . No other differences between groups regarding ROM , pain , or disability scores at any time interval were found . CONCLUSION KT may be of some assistance to clinicians in improving pain-free active ROM immediately after tape application for patients with shoulder pain . Utilization of KT for decreasing pain intensity or disability for young patients with suspected shoulder tendonitis/impingement is not supported . LEVEL OF EVIDENCE Therapy , level 1b- Abstract Scapula taping is a commonly used adjunctive treatment for shoulder im- pingement pathology . However , this intervention has not previously been subject to formal investigation . A pilot single-blind r and omized controlled trial was conducted to evaluate facilitatory taping as an adjunct to routine physiotherapy management . Twenty-two sub- jects with unilateral shoulder impingement symptoms were r and omized into a taping with routine physiotherapy or a routine physiotherapy only group . The intervention group had scapula taping applied three times per week for the first two weeks of their treatment . All subjects were assessed at baseline , then at 2 and 6 weeks after the commencement of treat- ment . Pain and functional ability were assessed using the Shoulder Pain and Disability In- dex , range of shoulder elevation , and self-reported pain on elevation . At 2 weeks , the taping group demonstrated a strong trend toward reduced pain both on self-reported activity ( SPADI pain subscale mean for taping 27.0 versus 41.5 for control ) and pain during mea- sured abduction ( mean VAS 22.8 for taped , 46.8 for control ) , statistical power being limited by small sample size . No similar trend was evident in the SPADI disability subscale . The magnitude of the differences was reduced at 6-week follow-up . This study provides prelimi- nary evidence for a short-term role for scapula taping as an adjunct to routine physiother- apy in the management of shoulder impingement symptoms but also highlights the need for consideration on a case basis relating to risk factors for skin reaction BACKGROUND Subacromial impingement syndrome ( SIS ) is the most common reason for shoulder pain . Ultrasound and laser are the physical therapy modalities , in conservative treatment of SIS . AIM The aim of this study was to define and compare the efficacy of ultrasound , laser and exercise in the treatment of SIS . DESIGN This was a r and omized controlled trial with-pre and post-treatment evaluations SETTING Out- patients referred to physical medicine and rehabilitation unit . POPULATION This study was performed on 52 patients with SIS . The patients were r and omly allocated into three groups METHODS The patients were treated five days a week for three weeks with hotpack+ultrasound+exercise ( the first group ) ; hotpack+laser+exercise ( the second group ) , or hotpack+exercise ( the third group ) . The pre and post treatment ranges of motion were measured in the patients . The visual analogue scale ( VAS ) was used to evaluate the severity of pain . Constant scoring was used to evaluate the shoulder functions and the results were compared after the treatment . RESULTS When the post-treatment results of the groups were compared with the pretreatment results , there was a statistically significant improvement in each of the three groups , in the pain , the range of motion and the functional improvement at the shoulder ( P<0.05 ) . However , the inter-group comparison did not reveal any statistically significant difference in the parameters indicating improvement ( P>0.05 ) . CONCLUSION The results of this study demonstrated that ultrasound and laser treatments were not superior to each other in the treatment of SIS . CLINICAL REHABILITATION IMPACT . Exercise treatment forms the base for the conservative treatment BACKGROUND Shoulder pain in nursing professionals may lead to limitations in occupational and daily activities and consequently interfere with quality of life . OBJECTIVE To compare the effects of two physical therapy programs which differed in the proprioceptive exercises used on the nursing professionals with rotator cuff disorder , according to quality of life , work satisfaction indicators , and pain intensity . METHOD This study was an experimental , r and omized , prospect i ve , comparative trial with quantitative data analysis . The data sampling was carried out between the months of June 2010 and July 2011 by means of a question naire containing socio-demographic and professional information , the Western Ontario Rotator Cuff Index ( WORC ) , the Occupational Stress Indicator ( OSI ) , and the Visual Numeric Scale ( VNS ) . Based on r and omization , subjects were divided into two groups . Group 1 ( control ) was su bmi tted to stretching and strengthening exercises and cryotherapy . Group 2 ( experimental ) was treated with the same protocol as the control group , with the addition of proprioception exercises . The data was analyzed by means of the Statistical Package for the Social Science version 16.0 for Windows . RESULTS After physical therapy intervention , significant reduction in pain levels occurred in both groups , with a significant improvement in quality of life for Group 2 . No changes were observed in the work satisfaction indicators after the two types of physical therapy interventions . CONCLUSIONS The proprioceptive exercises were important in the treatment of musculoskeletal disorders , however the results did not allow us to determine which treatment was the most effective as there was no significant difference between groups OBJECTIVE To investigate the effect of individualized manual physiotherapy and exercises compared with individualized exercises alone in patients with shoulder impingement syndrome . DESIGN R and omized controlled trial . SUBJECTS Patients with shoulder impingement of more than 4 weeks ' duration . METHODS Patients in the intervention group were treated with individually adapted exercises and examination-based physiotherapy . Controls were treated with individually adapted exercises only . Both groups had 10 treatment sessions over a period of 5 weeks and subsequently continued their exercises at home for another 7 weeks . Results were analysed at 5 and 12 weeks after the start of the study . Primary outcome measures were : Shoulder Pain and Disability Index , and Patient 's Global Impression of Change . Secondary outcome measures were : mean weekly pain score ; Generic Patient-Specific Scale ; and Patients ' Satisfaction with Treatment . RESULTS A total of 46 patients were r and omized to the intervention group and 44 to the control group . Although both groups showed significant improvements , there was no difference between groups for the primary and secondary outcomes at any time . Only the results for mean pain differed at 5 weeks in favour of the intervention group . CONCLUSION Individually adapted exercises were effective in the treatment of patients with shoulder impingement syndrome . Individualized manual physiotherapy contributed only a minor amount to the improvement in pain intensity . However , further research is necessary to confirm these results before definite recommendations can be made OBJECTIVES Rotator cuff tendinopathy is a common source of shoulder pain characterised by persistent and /or recurrent problems for a proportion of sufferers . The aim of this study was to pilot the methods proposed to conduct a substantive study to evaluate the effectiveness of a self-managed loaded exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy . DESIGN A single-centre pragmatic unblinded parallel group pilot r and omised controlled trial . SETTING One private physiotherapy clinic , northern Engl and . PARTICIPANTS Twenty-four participants with rotator cuff tendinopathy . INTERVENTIONS The intervention was a programme of self-managed loaded exercise . The control group received usual physiotherapy treatment . MAIN OUTCOMES Baseline assessment comprised the Shoulder Pain and Disability Index ( SPADI ) and the Short-Form 36 , repeated three months post r and omisation . RESULTS The recruitment target was met and the majority of participants ( 98 % ) were willing to be r and omised . 100 % retention was attained with all participants completing the SPADI at three months . Exercise adherence rates were excellent ( 90 % ) . The mean change in SPADI score was -23.7 ( 95 % CI -14.4 to -33.3 ) points for the self-managed exercise group and -19.0 ( 95 % CI -6.0 to -31.9 ) points for the usual physiotherapy treatment group . The difference in three month SPADI scores was 0.1 ( 95 % CI -16.6 to 16.9 ) points in favour of the usual physiotherapy treatment group . CONCLUSIONS In keeping with previous research which indicates the need for further evaluation of self-managed loaded exercise for rotator cuff tendinopathy , these methods and the preliminary evaluation of outcome offer a foundation and stimulus to conduct a substantive study Subacromial impingement syndrome ( SIS ) is a frequent cause of shoulder pain . Our purpose in this double-blinded , r and omized , and controlled study was to demonstrate whether the pulsed electromagnetic field ( PEMF ) provides additional benefit when used with other conservative treatment modalities in acute phase rehabilitation program of SIS . Forty-six patients with unilateral shoulder pain who had been diagnosed as having SIS were included in this trial . The cases were r and omly separated into two groups . All cases received a treatment program for 3 weeks consisting of Codman ’s pendulum exercises and subsequent cold pack gel application on shoulders with pain 5 times a day , restriction of daily activities that require the h and s to be used over the head , and meloxicam tablet 15 mg daily . One group was given PEMF ; the other group was given sham PEMF daily , 25 min per session , 5 days per week for 3 weeks . Shoulder pain during rest and activity and which causes disturbance of sleep was evaluated using a visual analogue scale , and total Constant score investigated shoulder function . Daily living activities were evaluated by shoulder disability question naire . Results were assessed before and after treatment . When compared with the baseline values , significant improvements in all these variables were observed at the end of the treatment in both groups ( p < 0.05 ) . No significant difference between treatments was observed for any of these variables ( p > 0.05 ) . There is no convincing evidence that electromagnetic therapy is of additional benefit in acute phase rehabilitation program of SIS STUDY DESIGN R and omized controlled trial with immediate follow-up . OBJECTIVES To evaluate the immediate effects of a low-amplitude , high-velocity thrust thoracic spine manipulation ( TSM ) on pain and scapular kinematics during elevation and lowering of the arm in individuals with shoulder impingement syndrome ( SIS ) . The secondary objective was to evaluate the immediate effects of TSM on scapular kinematics during elevation and lowering of the arm in individuals without symptoms . BACKGROUND Considering the regional interdependence among the shoulder and the thoracic and cervical spines , TSM may improve pain and function in individuals with SIS . Comparing individuals with SIS to those without shoulder pathology may provide information on the effects of TSM specifically in those with SIS . METHODS Fifty subjects ( mean ± SD age , 31.8 ± 10.9 years ) with SIS and 47 subjects ( age , 25.8 ± 5.0 years ) asymptomatic for shoulder dysfunction were r and omly assigned to 1 of 2 interventions : TSM or a sham intervention . Scapular kinematics were analyzed during elevation and lowering of the arm in the sagittal plane , and a numeric pain rating scale was used to assess shoulder pain during arm movement at preintervention and postintervention . RESULTS For those in the SIS group , shoulder pain was reduced immediately after TSM and the sham intervention ( mean ± SD preintervention , 2.9 ± 2.5 ; postintervention , 2.3 ± 2.5 ; P<.01 ; moderate effect size [ Cohen d = 0.2 ] ) . Scapular internal rotation increased 0.5 ° ± 0.02 ° ( P = .04 ; small effect size [ Cohen d<0.1 ] ) during elevation of the arm after TSM and sham intervention in the SIS group only . Subjects with and without SIS who received TSM and asymptomatic subjects who received the sham intervention had a significant increase ( 1.6 ° ± 2.7 ° ) in scapular upward rotation postintervention ( P<.05 ; small effect size [ Cohen d<0.2 ] ) , which was not considered clinical ly significant . Scapular anterior tilt increased 1.0 ° ± 4.8 ° during elevation and lowering of the arm postmanipulation ( P<.05 ; small effect size [ Cohen d<0.2 ] ) in the asymptomatic subjects who received TSM . CONCLUSION Shoulder pain in individuals with SIS immediately decreased after a TSM . The observed changes in scapular kinematics following TSM were not considered clinical ly important . LEVEL OF EVIDENCE Therapy , level 4 . J Orthop Sports Phys Ther 2014;44(7):475 - 487 . Epub 22 May 2014 . doi:10.2519/jospt.2014.4760 To study the effect of pulsed ultrasound in shoulder pains , 35 patients were treated with pulsed ultrasound and 37 patients with placebo ultrasound in a double-blind design . The therapy was given during inpatient rehabilitation , 10 - 12 treatments over 3 - 4 weeks . Treatment time was 10 minutes , frequency 1.0mHz , on-off ratio 1:4 and intensity 1.0w/cm2 . Follow-ups were done after 4 - 12 months . No differences ( p < 0.05 ) in outcomes were found between the groups after the treatment period or at follow-ups . These results discourage the adding of pulsed ultrasound therapy with the variables used to the conservative treatment of the painful shoulder Introduction Return to work following an occupational injury is a multifactoral process although many traditional clinic-based rehabilitation programs do not appreciate the importance of workplace factors . A r and omized controlled trial was conducted to investigate the effect of workplace-based rehabilitation program on the return to work outcome of work-related rotator cuff disorder , which is based on the therapeutic use of actual work facilities and work environment . Methods A total of 103 workers were recruited and r and omly assigned into Clinic-based Work Hardening ( CWH ) or Workplace-based Work Hardening ( WWH ) groups . The CWH group were given traditional generic work hardening training while WWH group received workplace-based work hardening training with rehabilitative principles of athletic rotator cuff pathology , biomechanics and specific job activities . Results After four weeks , a higher return to work rate was obtained in WWH group compared to CWH group ( 71.4 % vs. 37 % , p < 0.01 ) . A statistically significant difference ( p < 0.05 ) was also noted in lowering of self-reported shoulder problems and functional work capabilities in the WWH group versus the CWH group . Conclusion Workplace-based rehabilitation program appeared to be more effective in facilitating the return to work process of the injured worker as assessed immediately following intervention . In particular this approached was associated with many of the psychosocial workplace factors related to separation from the work routine . The influence of peer group and /or employer could be minimized . This initial attempt with rotator cuff injuries appears promising however long-term outcome needs to be determined The purpose of this clinical trial is to compare the effectiveness of a scapular-focused treatment with a control therapy in patients with shoulder impingement syndrome . Therefore , a r and omized clinical trial with a blinded assessor was used in 22 patients with shoulder impingement syndrome . The primary outcome measures included self-reported shoulder disability and pain . Next , patients were evaluated regarding scapular positioning and shoulder muscle strength . The scapular-focused treatment included stretching and scapular motor control training . The control therapy included stretching , muscle friction , and eccentric rotator cuff training . Main outcome measures were the shoulder disability question naire , diagnostic tests for shoulder impingement syndrome , clinical tests for scapular positioning , shoulder pain ( visual analog scale ; VAS ) , and muscle strength . A large clinical ly important treatment effect in favor of scapular motor control training was found in self-reported disability ( Cohen ’s d = 0.93 , p = 0.025 ) , and a moderate to large clinical ly important improvement in pain during the Neer test , Hawkins test , and empty can test ( Cohen ’s d 0.76 , 1.04 , and 0.92 , respectively ) . In addition , the experimental group demonstrated a moderate ( Cohen ’s d = 0.67 ) improvement in self-experienced pain at rest ( VAS ) , whereas the control group did not change . The effects were maintained at three months follow-up A systematic review of the literature was performed to evaluate the role of exercise in treating rotator cuff impingement and to synthesize a st and ard evidence -based rehabilitation protocol . Eleven r and omized , controlled trials ( level 1 and 2 ) evaluating the effect of exercise in the treatment of impingement were identified . Data regarding demographics , methodology , and outcomes of pain , range of motion , strength , and function were recorded . Individual components of each rehabilitation program were catalogued . Effectiveness was determined by statistical and clinical significance . Although many articles had method ologic concerns , the data demonstrate that exercise has statistically and clinical ly significant effects on pain reduction and improving function , but not on range of motion or strength . Manual therapy augments the effects of exercise , yet supervised exercise was not different than home exercise programs . Information regarding specific components of the exercise programs was synthesized into a gold st and ard rehabilitation protocol for future studies on the nonoperative treatment of rotator cuff impingement Shoulder impingement syndrome ( SIS ) is a complex , multi-factorial problem that is treated with a variety of different conservative options . One conservative option that has shown effectiveness is manual therapy to the thoracic spine . Another option , manual therapy to the cervical spine , has been studied only once with good results , evaluating short-term outcomes , in a small sample size . The purpose of this study was to investigate the benefit of neck manual therapy for patients with SIS . The study was a r and omised , single blinded , clinical trial where both groups received pragmatic , evidence -based treatment to the shoulder and one group received neck manual therapy . Subjects with neck pain were excluded from the study . Comparative pain , disability , rate of recovery and patient acceptable symptom state ( PASS ) measures were analyzed on the 68 subjects seen over an average of 56.1 days ( st and ard deviation (SD)=55.4 ) . Eighty-six percent of the sample reported an acceptable change on the PASS at discharge . There were no between-groups differences in those who did or did not receive neck manual therapy ; however , both groups demonstrated significant within-groups improvements . On average both groups improved 59.7 % ( SD=25.1 ) for pain and 53.5 % ( SD=40.2 ) for the Quick Disabilities of the Shoulder and H and Question naire ( QuickDASH ) from baseline . This study found no value when neck manual therapy was added to the treatment of SIS . Reasons may include the lack of therapeutic dosage provided for the manual therapy approach or the lack of benefit to treating the neck in subjects with SIS who do not have concomitant neck problems BACKGROUND Thoracic SMT can improve symptoms in patients with subacromial impingement syndrome . However , at this time the mechanisms of SMT are not well established . It is possible that changes in pain sensitivity may occur following SMT . OBJECTIVES To assess the immediate pain response in patients with shoulder pain following thoracic spinal manipulative therapy ( SMT ) using pressure pain threshold ( PPT ) , and to assess the relationship of change in pain sensitivity to patient-rated outcomes of pain and function following treatment . DESIGN R and omized Controlled Study . METHODS Subjects with unilateral subacromial impingement syndrome ( n = 45 ) were r and omly assigned to receive treatment with thoracic SMT or sham thoracic SMT . PPT was measured at the painful shoulder ( deltoid ) and unaffected regions ( contralateral deltoid and bilateral lower trapezius areas ) immediately pre- and post-treatment . Patient-rated outcomes were pain ( numeric pain rating scale - NPRS ) , function ( Pennsylvania Shoulder Score - Penn ) , and global rating of change ( GROC ) . RESULTS There were no significant differences between groups in pre-to post-treatment changes in PPT ( p ≥ 0.583 ) nor were there significant changes in PPT within either group ( p ≥ 0.372 ) following treatment . NPRS , Penn and GROC improved across both groups ( p < 0.001 ) , but there were no differences between the groups ( p ≥ 0.574 ) . CONCLUSION There were no differences in pressure pain sensitivity between participants receiving thoracic SMT versus sham thoracic SMT . Both groups had improved patient-rated pain and function within 24 - 48 h of treatment , but there was no difference in outcomes between the groups BACKGROUND Various manual therapy procedures are increasingly more often being used in the treatment of shoulder complex dysfunctions . The objective of the present study was to investigate whether manual therapy can improve the range of motion in the glenohumeral joint and alleviate pain in patients with chronic rotator cuff injuries MATERIAL AND METHODS The participants were r and omly assigned to an experimental group and a control group of 15 patients each . Both groups received a st and ard combination therapy involving TENS , ultrasound therapy and kinesiotherapy . Additionally , the experimental group took part in a treatment programme design ed by the authors composed of selected elements of various manual therapy techniques . Outcome evaluation focused on changes in the range of motion in the glenohumeral joint and changes in pain intensity ( VAS scale ) during the performance of functional tests . The results were subjected to statistical analysis . RESULTS More rapid and more significant pain reduction and more significant improvement in the range of motion of the glenohumeral joint across all movements tested were obtained in the experimental group . CONCLUSION The inclusion of manual therapy in st and ard comprehensive physiotherapy applied in the rehabilitation of patients with chronic rotator cuff injuries of the glenohumeral joint significantly improves treatment effectiveness OBJECTIVES To compare the effect of grade d physiotherapeutic training of the rotator cuff versus arthroscopic subacromial decompression in patients with subacromial impingement . METHODS R and omised controlled trial with 12 months ' follow up in a hospital setting . Ninety consecutive patients aged 18 to 55 years were enrolled . Symptom duration was between six months and three years . All fulfilled a set of diagnostic criteria for rotator cuff disease , including a positive impingement sign . Patients were r and omised either to arthroscopic subacromial decompression , or to physiotherapy with exercises aim ing at strengthening the stabilisers and decompressors of the shoulder . Outcome was shoulder function as measured by the Constant score and a pain and dysfunction score . " Intention to treat " analysis was used , with comparison of means and control of confounding variables by general equation estimation analysis . RESULTS Of 90 patients enrolled , 84 completed follow up ( 41 in the surgery group , 43 in the training group ) . The mean Constant score at baseline was 34.8 in the training group and 33.7 in the surgery group . After 12 months the mean scores improved to 57.0 and 52.7 , respectively , the difference being non-significant . No group differences in mean pain and dysfunction score improvement were found . CONCLUSIONS Surgical treatment of rotator cuff syndrome with subacromial impingement was not superior to physiotherapy with training . Further studies are needed to qualify treatment choice decisions , and it is recommended that sample s are stratified according to disability level Primary shoulder impingement syndrome is a common shoulder problem which , if treated ineffectively , can lead to more serious pathology and expensive treatment . This study examined whether subjects receiving joint mobilization and comprehensive treatment ( hot packs , active range of motion , physiologic stretching , muscle strengthening , soft tissue mobilization , and patient education ) would have improved pain , mobility , and function compared with similar patients receiving comprehensive treatment alone . Subjects were eight men and six women ( mean age = 52.9 years ) with primary shoulder impingement syndrome ( superolateral shoulder pain , decreased active humeral elevation , limited overhead function ) . Following r and om assignment to experimental ( N = 7 ) and control groups ( N = 7 ) , three blinded evaluators tested 24-hour pain ( visual analog scale ) , pain with subacromial compression test ( visual analog scale ) , active range of motion ( goniometry ) , and function ( reaching forward , behind the head , and across the body in an overhead position ) before and after nine treatments . One-tailed analyses of covariance ( baseline values as covariates ) showed that the experimental group had less 24-hour pain and pain with subacromial compression test but no differences in range of motion and function ( Mann-Whitney U ) compared with controls . The experimental group improved on all variables , while the control group improved only on mobility and function ( one-tailed , paired t tests ; Wilcoxon matched pairs ) . Age , side of dominance , duration of symptoms , treatment attendance , exercise quality , and adherence had no effect on the outcomes . Results may be affected by inadequate sample size , minimal capsular tightness , insensitive functional scale , nonspecific motion measurements , position at which mobilization treatment was given , or a strong effect of comprehensive treatment . Mobilization decreased 24-hour pain and pain with subacromial compression test in patients with primary shoulder impingement syndrome , but larger replication studies are needed to assess more clearly mobilization 's influence on motion and function The value of pulsed electromagnetic fields ( PEMF ) for the treatment of persistent rotator cuff tendinitis was tested in a double-blind controlled study in 29 patients whose symptoms were refractory to steroid injection and other conventional conservative measures . The treated group ( 15 patients ) had a significant benefit compared with the control group ( 14 patients ) during the first 4 weeks of the study , when the control group received a placebo . In the second 4 weeks , when all patients were on active coils , no significant differences were noted between the groups . This lack of difference persisted over the third phase , when neither group received any treatment for 8 weeks . At the end of the study 19 ( 65 % ) of the 29 patients were symptomless and 5 others much improved . PEMF therapy may thus be useful in the treatment of severe and persistent rotator cuff and possibly other chronic tendon lesions The aim of the study was to identify the differences in functionality of the upper limb in subjects suffering from shoulder impingement syndrome after intervention by two manual therapy protocol s. R and omized , single-blind study with a sample of 22 subjects ( 58 ± 10.86 years old ) divided into two groups . The conventional-group ( n = 11 ) received mobilizations of the shoulder and the experimental-group ( n = 11 ) was treated with soft tissue techniques in the cervical and upper thoracic regions . These two groups received electrotherapy and postural advices . The treatment lasted three weeks ( 15 daily sessions of 1 h and 30 min ) . Both active and passive range of motion ( ROM ) and self-perceived functionality of the upper limb ( DASH question naire ) were measured . The experimental group showed a significant improvement in the DASH scores and both groups improved mobility in the intra-group comparison pre-intervention versus post-intervention ( p < .05 ) , but not statistically significant differences were found in the between-group comparison ( p > .05 ) . Our results suggest that a combined treatment with electrotherapy , postural hygiene and manual therapy , regardless of the protocol , improves shoulder mobility and functionality STUDY DESIGN Case series . BACKGROUND Few studies have defined the dosage and specific techniques of manual therapy and exercise for rehabilitation for patients with subacromial impingement syndrome . This case series describes a st and ardized treatment program for subacromial impingement syndrome and the time course and outcomes over a 12-week period . CASE DESCRIPTION Ten patients ( age range , 19 - 70 years ) with subacromial impingement syndrome defined by inclusion and exclusion criteria were treated with a st and ardized protocol for 10 visits over 6 to 8 weeks . The protocol included a 3-phase progressive strengthening program , manual stretching , thrust and nonthrust manipulation to the shoulder and spine , patient education , activity modification , and a daily home exercise program of stretching and strengthening . Patients completed a history and measures of impairments and functional disability at 2 , 4 , 6 , and 12 weeks . OUTCOMES Treatment success was defined as both a 50 % improvement on the Disabilities of the Arm , Shoulder , and H and ( DASH ) score and a global rating of change of at least " moderately better . " At 6 weeks , 6 of 10 patients had a successful ( mean + /- SD ) DASH outcome score ( initial , 33.9 + /- 16.2 ; 6 weeks , 8.1 + /- 9.2 ) . At 12 weeks , 8 of 10 patients had a successful DASH outcome score ( initial , 33.1 + /- 14 ; 12 weeks , 8.3 + /- 6.4 ) . As a group , the largest improvement was in the first 2 weeks . The most common impairments for all 10 patients were rotator cuff and trapezius muscle weakness ( 10 of 10 patients ) , limited shoulder internal rotation motion ( 8 of 10 patients ) , and reduced kyphosis of the midthoracic area ( 7 of 10 patients ) . DISCUSSION A program aim ed at strengthening rotator cuff and scapular muscles , with stretching and manual therapy aim ed at thoracic spine and the posterior and inferior soft-tissue structures of the glenohumeral joint appeared to be successful in the majority of patients . This case series describes a comprehensive impairment-based treatment which result ed in symptomatic and functional improvement in 8 of 10 patients in 6 to 12 weeks . LEVEL OF EVIDENCE Therapy , level 4 Objectives Treatment for degenerative rotator cuff disease of the shoulder includes physiotherapy . Dynamic humeral centering ( DHC ) aims at preventing subacromial impingement , which contributes to the disease . The goal of this study was to assess the effectiveness of DHC . Method 69 patients with shoulder pain and impingement syndrome were prospect ively included in a single-centre r and omised trial with a 12-month follow-up . Patients and assessor were blinded to the study hypothesis and treatment , respectively . DHC and non-specific mobilisation as control were performed for 6 weeks , in 15 supervised individual outpatient sessions , and patients performed daily home exercises . The planned primary outcome was the Constant score including subscores for pain , activity , mobility and strength at 3 months . Secondary outcomes were the Constant score and subscores at 12 months , and medication use for pain at 3 and 12 months . Results The DHC group did not differ from the control group in the total Constant score at 3 months . However , the DHC group showed a higher Constant subscore for pain ( 12.2 ( SD 2.8 ) vs 9.9 ( 2.9 ) , least square means difference 2.1 , 95 % CI 0.7 to 3.5 , p=0.004 ) . At 3 months , the DHC group also showed a higher rate of no medication use ( 96.7 % vs 71 % , proportional difference 25.7 , 95 % CI 3.7 to 51.9 , p=0.012 ) . There was no other intergroup difference . Conclusions There was no difference in the total Constant score between DHC and controls . However , pain was improved at 3 months after DHC . The differences found in subscores for pain should be explored in future studies . Trial registration clinical trials.gov Identifier : NCT 01022775 Objectives : To compare the prognosis of subacromial impingement ( SAI ) stage II treated conservatively or with subacromial decompression . Methods : A follow‐up study after 4–8 years in a r and omized controlled trial ( RCT ) with 90 adult cases with SAI treated in a Danish hospital from 1996 to 2000 with grade d physiotherapy and exercises or arthroscopic subacromial decompression . Outcomes were proportion of time per year with income transfers ( indexed 0–1 ) , including total transfers ( marginalization ) , sick leave and disability pension obtained from the registry at the Ministry of Work . Self‐reported function , working capability , employment status and global improvement were obtained by question naire in September 2004 . The main outcomes are given as differences in development from baseline . Results : Seventy‐nine ( 88 % ) responded to the question naire and registry data were obtained from 81 . After 1 year the marginalization index increased by 0.45 [ 95 % confidence interval ( CI ) 0.35–0.56 ] for surgery and 0.25 ( 0.16–0.34 ) for physiotherapy . Cases undergoing surgery also tended to have more sick payments during the first year , but the difference was not significant . Four years after inclusion , changes in indices did not differ between treatment groups . Self‐reported outcomes after 4–8 years did not differ between treatment groups . Conclusion : The results of surgical decompression were equal to those of conservative treatment , and the surgery group had more income transferrals during the first year of follow‐up Scapular kinematics alterations have been found following muscle fatigue . Considering the importance of the lower trapezius in coordinated scapular movement , this study aim ed to investigate the effects of elastic taping ( Kinesio taping , KT ) for muscle facilitation on scapular kinematics of healthy overhead athletes following muscle fatigue . Twenty-eight athletes were evaluated in a crossover , single-blind , r and omized design , in three sessions : control ( no taping ) , KT ( KT with tension ) and sham ( KT without tension ) . Scapular tridimensional kinematics and EMG of clavicular and acromial portions of upper trapezius , lower trapezius and serratus anterior were evaluated during arm elevation and lowering , before and after a fatigue protocol involving repetitive throwing . Median power frequency decline of serratus anterior was significantly lower in KT session compared to sham , possibly indicating lower muscle fatigue . However , the effects of muscle fatigue on scapular kinematics were not altered by taping conditions . Although significant changes were found in scapular kinematics following muscle fatigue , they were small and not considered relevant . It was concluded that healthy overhead athletes seem to present an adaptive mechanism that avoids the disruption of scapular movement pattern following muscle fatigue . Therefore , these athletes do not benefit from the use of KT to assist scapular movement under the conditions tested Background : Subacromial impingement syndrome ( SAIS ) is a painful condition result ing from the entrapment of anatomical structures between the anteroinferior corner of the acromion and the greater tuberosity of the humerus . Objective : The aim of this study was to evaluate the short-term effectiveness of high-intensity laser therapy ( HILT ) versus ultrasound ( US ) therapy in the treatment of SAIS . Design : The study was design ed as a r and omized clinical trial . Setting : The study was conducted in a university hospital . Patients : Seventy patients with SAIS were r and omly assigned to a HILT group or a US therapy group . Intervention : Study participants received 10 treatment sessions of HILT or US therapy over a period of 2 consecutive weeks . Measurements : Outcome measures were the Constant-Murley Scale ( CMS ) , a visual analog scale ( VAS ) , and the Simple Shoulder Test ( SST ) . Results : For the 70 study participants ( 42 women and 28 men ; mean [ SD ] age=54.1 years [ 9.0 ] ; mean [ SD ] VAS score at baseline=6.4 [ 1.7 ] ) , there were no between-group differences at baseline in VAS , CMS , and SST scores . At the end of the 2-week intervention , participants in the HILT group showed a significantly greater decrease in pain than participants in the US therapy group . Statistically significant differences in change in pain , articular movement , functionality , and muscle strength ( force-generating capacity ) ( VAS , CMS , and SST scores ) were observed after 10 treatment sessions from the baseline for participants in the HILT group compared with participants in the US therapy group . In particular , only the difference in change of VAS score between groups ( 1.65 points ) surpassed the accepted minimal clinical ly important difference for this tool . Limitations : This study was limited by sample size , lack of a control or placebo group , and follow-up period . Conclusions : Participants diagnosed with SAIS showed greater reduction in pain and improvement in articular movement functionality and muscle strength of the affected shoulder after 10 treatment sessions of HILT than did participants receiving US therapy over a period of 2 consecutive weeks Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists OBJECTIVES A r and omized , double-blind , clinical trial study was conducted with the aim of determining the efficacy of adding laser ( 830 nm ) to ultrasound ( US ) and exercise for the management of shoulder tendonitis . METHODS 42 subjects ( n=21 , in adding laser group and n=21 , in US and exercise group ) received a course of 10 sessions treatment over one month in the shoulder region . Outcome measures such as Visual Analogue Scale ( VAS ) , Tenderness Severity Scale ( TSS ) , Constant Murley Score ( CMS ) and Manual Muscle Testing ( MMT ) were performed before treatment and at the end of 4 weeks treatment . In addition , follow up were performed 2 months after the end of treatment based on the degree of pain improvement . RESULTS VAS , TSS and CMS improved significantly ( P=0.001 ) in both groups , however the muscle strengths only improved significantly in adding laser group ( P < 0.01 ) . CONCLUSION It seems that both protocol s of physical therapy interventions were effective in relieving the signs and symptoms of shoulder tendonitis . Furthermore , adding low level laser therapy ( LLLT ) to the US and exercise was more efficient in improving the muscle strength in patients with shoulder tendonitis over a period of three months . However , it should be emphasized that , the current results might be due to the effects of laser and exercise instead of laser , us and exercise ( as we had no independent group for US ) Rotator cuff tendinitis is one of the main causes of shoulder pain . The objective of this study was to evaluate the possible additive effects of low-power laser treatment in combination with conventional physiotherapy endeavors in these patients . A total of 50 patients who were referred to the Physical Medicine and Rehabilitation Clinic with shoulder pain and rotator cuff disorders were selected . Pain severity measured with visual analogue scale ( VAS ) , abduction , and external rotation range of motion in shoulder joint was measured by goniometry , and evaluation of daily functional abilities of patients was measured by shoulder disability question naire . Twenty-five of the above patients were r and omly assigned into the control group and received only routine physiotherapy . The other 25 patients were assigned into the experimental group and received conventional therapy plus low-level laser therapy ( 4 J/cm2 at each point over a maximum of ten painful points of shoulder region for total 5 min duration ) . The above measurements were assessed at the end of the third week of therapy in each group and the results were analyzed statistically . In both groups , statistically significant improvement was detected in all outcome measures compared to baseline ( p < 0.05 ) . Comparison between two different groups revealed better results for control of pain ( reduction in VAS average ) and shoulder disability problems in the experimental group versus the control ( 3.1 ± 2.2 vs. 5 ± 2.6 , p = 0.029 and 4.4 ± 3.1 vs. 8.5 ± 5.1 , p = 0.031 , respectively ) after intervention . Positive objective signs also had better results in the experimental group , but the mean range of active abduction ( 144.92 ± 31.6 vs. 132.80 ± 31.3 ) and external rotation ( 78.0 ± 19.5 vs. 76.3 ± 19.1 ) had no significant difference between the two groups ( p = 0.20 and 0.77 , respectively ) . As one of physical modalities , gallium-arsenide low-power laser combined with conventional physiotherapy has superiority over routine physiotherapy from the view of decreasing pain and improving the patient ’s function , but no additional advantages were detected in increasing shoulder joint range of motion in comparison to other physical agents The aim of this clinical trial was to evaluate the effectiveness of therapeutic MD on pain , functional capacity , muscle strength , quality of life , and depression in patients with subacromial impingement syndrome ( SIS ) . A total of 40 inpatient subjects with definite SIS were included in this study . These patients were sequentially r and omized into 2 groups . Group 1 ( n = 20 ) received therapeutic MD . Group 2 ( n = 20 ) was served as control group and received sham MD . Superficial heat and exercise program were given to both groups . Both of the programs were performed 5 times weekly for 3 weeks . Patients were assessed before treatment ( BT ) , after treatment ( AT ) , and at a 1-month follow-up ( F ) . Outcome measures included visual analogue scale , goniometry , Shoulder Pain and Disability Index , Shoulder Disability Question naire , shoulder isokinetic muscle testing , h and grip strength , Short Form 36 , and Beck Depression Index . The patients with SIS in each group had significant improvements in pain , shoulder ROM , disability , shoulder muscles and grip strength , quality of life , and depression AT and F when compared with their initial status ( P < 0.05 ) . There was no statistically significant difference between the groups according to all the parameters regarding the change scores between AT – BT test and F – BT test ( P > 0.05 ) . A 2,450-MHz MD regimen showed no beneficial effects in patients with SIS , so the superficial heat and exercise program , as it is efficient , may be preferable for the treatment of SIS , alone OBJECTIVE The aim of this study was to compare the effectiveness of low-level laser therapy and ultrasound therapy in the treatment of subacromial impingement syndrome . MATERIAL S AND METHODS Thirty one patients with subacromial impingement syndrome were r and omly assigned to low-level laser therapy group ( n=16 ) and ultrasound therapy group ( n=15 ) . Study participants received 10 treatment sessions of low-level laser therapy or ultrasound therapy over a period of two-consecutive weeks ( five days per week ) . Outcome measures ( visual analogue pain scale , Shoulder Pain and Disability Index -SPADI- , patient 's satisfactory level and sleep interference score ) were assessed before treatment and at the 1st and 3rd months after treatment . All patients were analyzed by the intent-to-treat principle . RESULTS Mean reduction in VAS pain , SPADI disability and sleep interference scores from baseline to after 1 month , and 3 months of treatment was statistically significant in both groups ( P < 0.05 ) . However , there was no significant difference in the mean change in VAS pain , SPADI disability and sleep interference scores between the two groups ( P > 0.05 ) . The mean level of patient satisfaction in group 1 at the first and third months after treatment was 72.45 ± 23.45 mm and 71.50 ± 16.54 mm , respectively . The mean level of patient satisfaction in group 2 at the first and third months after treatment was 70.38 ± 21.52 mm and 72.09 ± 13.42 mm , respectively . There was no significant difference in the mean level of patient satisfaction between the two groups ( p > 0.05 ) . CONCLUSIONS The results suggest that efficacy of both treatments were comparable to each other in regarding reducing pain severity and functional disability in patients with subacromial impingement syndrome . Based on our findings , we conclude that low-level laser therapy may be considered as an effective alternative to ultrasound based therapy in patients with subacromial impingement syndrome especially ultrasound based therapy is contraindicated The subacromial syndrome is the most common source of shoulder pain . The mainstays of conservative treatment are non-steroidal anti-inflammatory drugs and exercise therapy . Recently , low-level laser therapy ( LLLT ) has been popularized in the treatment of various musculoskeletal disorders . The aim of this study is to evaluate the additive effects of LLLT with exercise in comparison with exercise therapy alone in treatment of the subacromial syndrome . We conducted a r and omised clinical study of 80 patients who presented to clinic with subacromial syndrome ( rotator cuff and biceps tendinitis ) . Patients were r and omly allocated into two groups . In group I ( n = 40 ) , patients were given laser treatment ( pulsed infrared laser ) and exercise therapy for ten sessions during a period of 2 weeks . In group II ( n = 40 ) , placebo laser and the same exercise therapy were given for the same period . Patients were evaluated for the pain with visual analogue scale ( VAS ) and shoulder range of motion ( ROM ) in an active and passive movement of flexion , abduction and external rotation before and after treatment . In both groups , significant post-treatment improvements were achieved in all parameters ( P = 0.00 ) . In comparison between the two groups , a significant improvement was noted in all movements in group I ( P = 0.00 ) . Also , there was a substantial difference between the groups in VAS scores ( P = 0.00 ) which showed significant pain reduction in group I. This study indicates that LLLT combined exercise is more effective than exercise therapy alone in relieving pain and in improving the shoulder ROM in patients with subacromial syndrome OBJECTIVE The study investigated the effectiveness of stretching , strengthening exercises , and the scapular stabilization exercises on the pain , shoulder range of motion ( ROM ) , muscle strength , joint position sense ( JPS ) , scapular dyskinesis and quality of life ( OL ) in the patients with subacromial impingement syndrome ( SIS ) . METHODS 27 women and 13 men , mean age 51 ( 24 - 71 ) years old , were included in this study . All the patients were separated into 2 groups according to simple r and om table . Stretching and strengthening exercises were given to the group I ( n=20 ) and scapular stabilization exercises were added to the group II ( n=20 ) . The pain severity , shoulder ROM , muscle strength , JPS , lateral scapular slide test ( LSST ) , Western Ontario Rotator Cuff ( WORC ) Index were evaluated before and after treatment . Patients completed a 6-week rehabilitation program , three times a week . RESULTS The results showed that all measurements improved statistically in both groups after treatment ( p < 0.05 ) . And the improvements in the muscle strength , JPS and scapular dyskinesia were significantly different in group II ( p < 0.05 ) . CONCLUSION It is suggested that in the treatment of SIS ; scapular stabilization exercises , given with stretching and strengthening exercises , can be more effective in increasing the muscle strength , developing the JPS and decreasing the scapular dyskinesis OBJECTIVE --To compare the effectiveness of arthroscopic surgery , a supervised exercise regimen , and placebo soft laser treatment in patients with rotator cuff disease ( stage II impingement syndrome ) . DESIGN --R and omised clinical trial . SETTING --Hospital departments of orthopaedics and of physical medicine and rehabilitation . PATIENTS --125 patients aged 18 - 66 who had had rotator cuff disease for at least three months and whose condition was resistant to treatment . INTERVENTIONS --Arthroscopic subacromial decompression performed by two experienced surgeons ; exercise regimen over three to six months supervised by one experienced physiotherapist ; or 12 sessions of detuned soft laser treatment over six weeks . MAIN OUTCOME MEASURES --Change in the overall Neer shoulder score ( pain during previous week and blinded evaluation of function and range of movement by one clinician ) after six months . RESULTS --No differences were found between the three groups in duration of sick leave and daily intake of analgesics . After six months the difference in improvement in overall Neer score between surgery and supervised exercises was 4.0 ( 95 % confidence interval -2 to 11 ) and 2.0 ( -1.4 to 5.4 ) after adjustment for sex . The condition improved significantly compared with placebo in both groups given the active treatments . Treatment costs were higher for those given surgery ( 720 pounds v 390 pounds ) . CONCLUSIONS --Surgery or a supervised exercise regimen significantly , and equally , improved rotator cuff disease compared with placebo BACKGROUND Kinesiological taping ( KT ) is commonly used to improve symptoms associated with musculoskeletal disorders . However , review of the literature revealed minimal evidence to support the use of KT in treatment of shoulder disorders and controversy exists regarding the effect of KT in patients with shoulder impingement syndrome ( SIS ) . OBJECTIVE The purpose of this study was to investigate the effect of KT on pain intensity during movement , pain experienced during the night ( nocturnal pain ) , and pain-free shoulder range of motion ( ROM ) immediately after taping , after three days and after one week , in patients with SIS . DESIGN R and omized , Double blinded , Placebo-controlled design . PARTICIPANTS A total of 30 patients with SIS participated in this study . Patients were assigned r and omly to a control ( N = 15 ) and an experimental group ( N = 15 ) . METHODS The patients in the experimental group received a st and ardized therapeutic KT . The st and ardized , placebo neutral KT was applied for control group . KT was applied two times with a three day interval , remaining on during the 3 day interval . Both groups followed the same procedures . Pain-free active ROM during shoulder abduction , flexion , and elevation in the scapular plane was measured . Visual analogue scale ( VAS ) for pain intensity during movement or nocturnal pain and was assessed at baseline , immediately after KT , after three days , and one week after KT . RESULTS The result of repeated measures ANOVA showed a significant change in pain level during movement , nocturnal pain , and pain-free ROM ( p = 0.000 ) after KT in the experimental group . In the ANCOVA , controlling for pre-test scores , change in pain level at movement ( p = 0.009 ) and nocturnal pain ( p = 0.04 ) immediately after KT was significantly greater in the experimental group than in control group . There was no significant difference in ROM measures ( p > 0.05 ) between groups immediately after KT . No significant differences were found between the two groups in the after one week measurements of pain intensity and shoulder ROM . CONCLUSION The KT produces an immediate improvement in the pain intensity at movement and nocturnal pain in patients with SIS . LEVEL OF EVIDENCE 1 BACKGROUND Traditional rehabilitation improves pain and function in patients with shoulder impingement syndrome . Neurocognitive rehabilitation has shown to be highly effective after surgical reconstruction of the anterior cruciate ligament . However , its effects in patients with shoulder impingement syndrome have not yet been established . AIM The aim of the study was to compare the effects of neurocognitive therapeutic exercise , based on proprioception and neuromuscular control , on pain and function in comparison to traditional therapeutic exercise in patients with shoulder impingement syndrome . DESIGN Single-blind r and omized , non-inferiority clinical trial . SETTING Outpatient clinic of Geriatrics and Physiatrics , University Hospital . POPULATION Forty-eight patients with shoulder impingement syndrome ( Neer stage I ) and pain lasting for at least three months . METHODS Participants were r and omly allocated ( 1:1 ) to either neurocognitive therapeutic exercise or traditional therapeutic exercise . Both treatments were provided one-hour session , three times a week for five weeks . The primary outcome measure was the short form of the Disability of the Arm , Shoulder and H and Question naire ( Quick-DASH question naire ) for the assessment of physical ability and symptoms of the upper extremity . SECONDARY OUTCOME MEASURES Constant-Murley shoulder outcome score for the determination of range of motion , pain and strength ; American Shoulder and Elbow Surgeons Society st and ardized shoulder assessment form for the evaluation of physical ability in daily-living tasks ; a visual analogue scale for pain assessment at rest and during movements ; Likert score for the estimation of participant satisfaction . ENDPOINTS before treatment , end of treatment , 12 and 24 weeks after the completion of each intervention for all outcome measures , except for the Likert score that was evaluated only at the end of treatment . FOLLOW-UP 24 weeks . RESULTS At the end of treatment and at follow-up , both treatment groups experienced improvements in all outcomes measures relative to baseline values , except for the visual analogue scale at rest that was unaffected by traditional therapeutic exercise . For all outcome measures , changes over time were greater in the neurocognitive therapeutic exercise group relative to the traditional therapeutic exercise group . The level of satisfaction with treatment was higher for participants in the neurocognitive therapeutic exercise group . CONCLUSION Neurocognitive rehabilitation is effective in reducing pain and improving function in patients with shoulder impingement syndrome , with benefits maintained for at least 24 weeks . CLINICAL REHABILITATION IMPACT skills and function of the shoulder can greatly benefit from neurocognitive rehabilitation OBJECTIVES The aim of this r and omized controlled study was to assess the efficacy of manual therapy in the treatment of patients with symptomatic supraspinatus tendinopathy . METHODS Seventy-seven patients ( age range , 30 to 55 years ) with supraspinatus tendinopathy , were r and omly assigned to one of the three treatment groups : a supervised exercise program ( Group 1 ) , a supervised exercise program combined with joint and soft tissue mobilization ( Group 2 ) , or a home-based rehabilitation program ( Group 3 ) . All patients had rehabilitation for 12 weeks . Pain level was evaluated with a visual analogue scale ( VAS ) and the range of motion ( ROM ) was measured with a goniometer . The Modified American Shoulder and Elbow Surgery ( MASES ) score was used in functional assessment . Flexion , abduction , internal and external rotation strengths were measured with a manual muscle test . All patients were evaluated before , and at the 4th and 12th week of the rehabilitation . RESULTS All groups experienced significant decrease in pain and an increase in shoulder muscle strength and function by both the 4th and 12th weeks of treatment ( p<0.05 ) . There was no significant difference between the groups in terms of function ( p>0.05 ) . However , the greatest improvement in functionality was found in Group 2 . CONCLUSION Supervised exercise , supervised and manual therapy , and home-based exercise are all effective and promising methods in the rehabilitation of the patients with subacromial impingement syndrome . The addition of an initial manual therapy may improve the results of the rehabilitation with exercise Abstract The purpose of this double-blind , r and omized controlled pilot study was to compare the effectiveness of four physical therapy interventions in the treatment of primary shoulder impingement syndrome : 1 ) supervised exercise only , 2 ) supervised exercise with glenohumeral mobilizations , 3 ) supervised exercise with a mobilization-with-movement ( MWM ) technique , or 4 ) a control group receiving only physician advice . Thirty-three subjects diagnosed with primary shoulder impingement were r and omly assigned to one of these four groups . Main outcome measures included 24-hour pain ( VAS ) , pain with the Neer and Hawkins-Kennedy tests , shoulder active range of motion ( AROM ) , and shoulder function ( SPADI ) . Repeated- measures analyses indicated significant decreases in pain , improved function , and increases in AROM . Univariate analyses on the percentage of change from pre- to post-treatment for each dependent variable found no statistically significant differences ( P<0.05 ) between the four groups . Although not significant , the MWM and mobilization groups had a higher percentage of change from pre- to post-treatment on all three pain measures ( VAS , Neer , Hawkins-Kennedy ) . The three intervention groups had a higher percentage of change on the SPADI . The MWM group had the highest percentage of change in AROM , and the mobilization group had the lowest . This pilot study suggests that performing glenohumeral mobilizations and MWM in combination with a supervised exercise program may result in a greater decrease in pain and improved function although studies with larger sample s and discriminant sampling methods are needed BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . OBJECTIVE To assess pain , function , quality of life , and muscle strength in patients with shoulder impingement syndrome who participated in muscle strengthening exercises . METHODS A total of 60 patients diagnosed with shoulder impingement syndrome were selected from the clinics of the Federal University of São Paulo and r and omly distributed into experimental and control groups . Patients were evaluated regarding pain , function , quality of life , muscle strength , and the number of antiinflammatory drugs and analgesics taken . Patients then participated in the progressive resistance training program for the musculature of the shoulder , which was held twice a week for 2 months , while the control group remained on a waiting list . RESULTS Sixty patients were r and omly allocated to the experimental group ( 21 women and 9 men , mean age 56.3 years ) and control group ( 25 women and 5 men , mean age 54.8 years ) . Patients from the experimental group showed an improvement from 4.2 cm to 2.4 cm on a 10-cm visual analog scale ( P < 0.001 ) regarding pain at rest and from 7.4 cm to 5.2 cm ( P < 0.001 ) regarding pain during movement . Function went from 44.0 to 33.2 ( P < 0.007 ) using the Disabilities of the Arm , Shoulder , and H and assessment and domains from the Short Form 36 . There was a statistically significant difference in improvement in pain and function between patients in the experimental group and those in the control group ( P < 0.05 ) . CONCLUSION The progressive resistance training program for the musculature of the shoulder in patients with shoulder impingement syndrome was effective in reducing pain and improving function and quality of life OBJECTIVES To evaluate the short-term efficacy of muscle shortening manoeuvre ( MSM ) , by inducing an increase in strength of the shoulder muscles , for the treatment of shoulder impingement syndrome ( SIS ) . METHODS Sixty subjects ( mean age : 58.6 years ) with SIS were assigned to one of 3 different treatment interventions : 1 ) MSM : a series of fast accelerations in the upward direction was applied to the upper limb that was also su bmi tted to forces acting in the opposite direction ( added mass ) ; 2 ) traditional physiotherapeutic technique : scapulothoracic gliding ; 3 ) simple traction : the added mass was applied to the limb without the series of fast accelerations . Pain intensity , Neer 's impingement sign , range of motion and muscle strength were assessed . Ultrasound ( US ) examination was performed before , immediately after and 30 days after each treatment to study the width of the subacromial-subdeltoid bursa , long biceps tendon sheath and acromioclavicular joint . Impingement was evaluated by dynamic examination . RESULTS After treatment with MSM , pain was significantly reduced ( p<0.001 ) , Neer 's impingement sign was negative , range of motion and muscle strength were increased . US examination showed that the widths of the subacromial-subdeltoid bursa ( p<0.001 ) , long biceps tendon sheath ( p<0.001 ) and acromioclavicular joint ( p<0.001 ) were significantly reduced ; impingement was no more detected . After 30 days , improvement in clinical and US findings was maintained . In the two control groups , no significant changes were observed after treatment . CONCLUSIONS Clinical and US findings demonstrate that MSM , by inducing an increase in muscle strength , is effective in the short-term treatment of SIS BACKGROUND AND PURPOSE There is no definitive evidence for the efficacy of the physical therapy interventions used for patients with impingement syndrome . The purpose of this study was to compare manual acupuncture and continuous ultrasound , both applied in addition to home exercises , for patients diagnosed with impingement syndrome . SUBJECTS AND METHODS Eighty-five patients with clinical signs of impingement syndrome were r and omly assigned to either a group that received acupuncture ( n=44 ) or a group that received ultrasound ( n=41 ) . Both interventions were given by physical therapists twice a week for 5 weeks in addition to a home exercise program . Scores from 3 shoulder disability measures , combined in the analysis , measured change during a period of 12 months . RESULTS Both groups improved , but the acupuncture group had a larger improvement in the combined score . DISCUSSION AND CONCLUSION The results suggest that acupuncture is more efficacious than ultrasound when applied in addition to home exercises Abstract Objective : To compare the efficacy of physiotherapy , manipulation , and corticosteroid injection for treating patients with shoulder complaints in general practice . Design : R and omised , single blind study . Setting : Seven general practice s in the Netherl and s. Subjects : 198 patients with shoulder complaints , of whom 172 were divided , on the basis of physical examination , into two diagnostic groups : a shoulder girdle group ( n = 58 ) and a synovial group ( n = 114 ) . Interventions : Patients in the shoulder girdle group were r and omised to manipulation or physiotherapy , and patients in the synovial group were r and omised to corticosteroid injection , manipulation , or physiotherapy . Main outcome measures : Duration of shoulder complaints analysed by survival analysis . Results : In the shoulder girdle group duration of complaints was significantly shorter after manipulation compared with physiotherapy ( P < 0.001 ) . Also the number of patients reporting treatment failure was less with manipulation . In the synovial group duration of complaints was shortest after corticosteroid injection compared with manipulation and physiotherapy ( P < 0.001 ) . Drop out due to treatment failure was low in the injection group ( 17 % ) and high in the manipulation group ( 59 % ) and physiotherapy group ( 51 % ) . Conclusions : For treating shoulder girdle disorders , manipulation seems to be the preferred treatment . For the synovial disorders , corticosteroid injection seems the best treatment . Key messages Many patients with shoulder complaints are treated in general practice , but there has been little evaluation of different treatments In this single blind r and omised trial we investigated the effect of corticosteroid injection , manipulation , and physiotherapy on the duration of shoulder complaints among patients treated in general practice Patients were divided into two diagnostic groups : those with complaints originating from the synovial structures and those whose complaints originated from the shoulder girdle The first group was treated by injection , manipulation , or physiotherapy : those receiving injection showed quickest recovery and only 17 % of patients dropped out because of treatment failure , compared with 51 % in physiotherapy group and 59 % in manipulation group Patients with a shoulder girdle disorder were treated by manipulation or physiotherapy : duration of complaints was significantly shorter after manipulation , and there was only 20 % drop out in this group compared with 45 % in physiotherapy AIM Rotator cuff problems are common causes of pain and restriction of movement in shoulder . The aim of this study to compare the effect of intra-articular injection of corticosteroid and conventional transcutaneous electrical nerve stimulator ( TENS ) treatment in treatment of rotator cuff tendinitis . METHODS Subjects were r and omly allocated into Group 1 ( intra-articular injection of corticosteroid ) and Group 2 ( conventional transcutaneous electrical nerve stimulation-TENS ) . Outcome measurements were performed using the Visual Analogue Scale ( VAS ) for pain , range of motion ( ROM ) , the Shoulder Disability Question naire ( SDQ ) , the Short Form-36 ( SF-36 ) , and Beck Depression Scale ( BDS ) question naires and paracetamol consumption . RESULTS In both groups , significant improvement was observed in all weeks in VAS , ROM and SDQ scores ( P<0.05 ) . Improvement was detected in most of the SF36 scores at the end of the treatment in both groups ( P<0.05 ) , while no significant change was observed in BDI score ( P>0.05 ) . In both treatment groups , paracetamol consumption decreased in time ( P<0.05 ) . When the groups were compared , a significant difference was found between the groups in favor of Group 1 in terms of VAS-at night and VAS-at rest in weeks 1 , 4 and 12 , and VAS-during movement in week 1 and 12 ( P<0.05 ) . The comparison of two groups revealed a significant difference in favor of Group 1 in weeks 1 in the passive abduction and the active and passive IR ROM measurements ( P<0.05 ) . There was also a significant difference in favor of Group 1 observed in weeks 1 in SDQ scores ( P<0.05 ) . CONCLUSION Intra-articular injection of corticosteroid and conventional TENS are efficient in the treatment of rotator cuff tendinitis . When two treatments are compared , it may be concluded that intra-articular steroid injection was more effective especially in the first weeks regarding pain , ROM and disability . Otherwise , use of TENS allow to patients to increase activity level , improve function and quality of life like that in our study . TENS , as it is cheaper , non-invasive , more easily performed and efficient , may be preferable for the treatment of shoulder pain . Further studies are needed to include these results in the prospect i ve treatment guidelines Purpose . To investigate the effectiveness of low-level laser therapy ( LLLT ) in addition to exercise programme on shoulder function in subacromial impingement syndrome ( SAIS ) . Method . Sixty-seven patients with SAIS were r and omly assigned to either a group that received laser ( n = 34 ) or a group that received placebo Laser ( n = 26 ) . Pain , functional assessment , disability and muscle strength of shoulder were assessed before and after a 3-week rehabilitation programme . Besides Laser or placebo Laser , superficial cold and progressive exercise programme were administered to both groups , 5 days a week , for 3 weeks . A progressive exercise programme that was done daily twice under supervision in clinic and at home was given to the patients . Results . After the treatment , all outcome measurements had shown significant improvement except muscle strength in both the groups . When the parameters of the improvement were compared , there were no significant differences between the two groups after treatment . Conclusion . We concluded that there is no fundamental difference between LLLT and placebo LLLT when they are supplementing an exercise programme for rehabilitation of patients with shoulder impingement syndrome Thirty-five patients with rotator cuff tendinitis were r and omly allocated to active ( CB Medico Master III 830 nm Ga As AL diode ) laser or dummy laser treatment twice weekly for 8 weeks . Movement range , painful arc score , resisted movement score and responses to visual analogue scales for night pain , rest pain , movement pain and functional limitation were measured second weekly . All responses improved from baseline but there was no difference between the two groups . These results fail to demonstrate the effectiveness of laser therapy in rotator cuff tendinitis OBJECTIVE The purpose of this study was to compare the effects of manual therapy with exercise to kinesiotaping with exercise for patients with subacromial impingement syndrome . METHODS R and omized clinical before and after trial was used . Fifty-four patients diagnosed as having subacromial impingement syndrome who were referred for outpatient treatment were included . Eligible patients ( between 30 and 60 years old , with unilateral shoulder pain ) were r and omly allocated to 2 study groups : kinesiotaping with exercise ( n = 28 ) or manual therapy with exercise ( n = 26 ) . In addition , patients were advised to use cold packs 5 times per day to control for pain . Visual analog scale for pain , Disability of Arm and Shoulder Question naire for function , and diagnostic ultrasound assessment for supraspinatus tendon thickness were used as main outcome measures . Assessment s were applied at the baseline and after completing 6 weeks of related interventions . RESULTS At the baseline , there was no difference between the 2 group characteristics ( P > .05 ) . There were significant differences in both groups before and after treatment in terms of pain decrease and improvement of Disability of Arm and Shoulder Question naire scores ( P < .05 ) . No difference was observed on ultrasound for tendon thickness after treatment in both groups ( P > .05 ) . The only difference between the groups was at night pain , result ing in favor of the kinesiotaping with exercise group ( P < .05 ) . CONCLUSION For the group of subjects studied , no differences were found between kinesiotaping with exercise and manual therapy with exercise . Both treatments may have similar results in reducing pain and disability in subacromial impingement in 6 weeks The effectiveness of arthroscopic surgery , supervised exercises , and placebo was compared in 125 patients with rotator cuff disease ( impingement syndrome stage II ) in a r and omized clinical trial . The median age was 48 years , and the median duration of complications was 1 to 2 years . The treatments were arthroscopic subacromial decompression performed by 2 experienced surgeons , an exercise regimen supervised for 3 to 6 months by 1 experienced physiotherapist , or 12 sessions of detuned soft laser ( placebo ) for 6 weeks . The criterion for success was a Neer shoulder score > 80 . Fifteen ( 50 % ) and 11 ( 22 % ) of the patients r and omized to placebo and exercises , respectively , had surgery during the 2 1/2-year follow-up period and were classified as having failure with the treatments . The success rate was higher ( P < .01 ) for patients r and omized to surgery ( 26 of 38 ) and exercises ( 27 of 44 ) compared with the placebo group ( 7 of 28 ) . The odds ratio for success after surgery compared with exercises was 1.5 ( 95 % confidence interval 0.6 to 3.7 ; P = .49 ) . Including all patients who underwent operation , the success rate in those not on sick leave ( 19 of 21 ) before surgery was higher compared with those on sick leave ( 18 of 36 ) ( adjusted odds ratio 5.6 [ 1.2 to 29.2 ] ) . Similar results were observed for patients not receiving versus those receiving regular pain medication before surgery ( adjusted odds ratio 4.2 [ 1.2 to 15.8 ] ) The aim of this prospect i ve , r and omized clinical study was to compare the effectiveness of two physical therapy treatment approaches for impingement syndrome , either by joint and soft tissue mobilization techniques or by a self-training program . Thirty patients ( Group 1 , n = 15 ; Group 2 , n = 15 ) with the diagnosis of an outlet impingement syndrome of the shoulder were treated either by strengthening the depressors of the humeral head with a guided self-training program ( Group 1 , age 49.5 ± 7.9 years ) , or by joint and soft tissue mobilization techniques ( Group 2 , age 48.1 ± 7.5 years ) . Group 1 was instructed with the active range of motion ( ROM ) , stretching and strengthening exercise program including rotator cuff muscles , rhomboids , levator scapulae and serratus anterior with an elastic b and at home at least seven times a week for 10–15 min and Group 2 received a prescription for 12 sessions of joint and soft tissue mobilization techniques , ice application , stretching and strengthening exercise programs and patient education in clinic for three times per week . All patients were tested with visual analog scale ( VAS ) for pain level , goniometric measurement for ROM and algometry for the pain threshold . Function was measured with a functional assessment question naire . The VAS ( 10 cm ) used to measure pain with functional activities and the functional assessment question naire ( Neer ) were also measured 3 months after the initiation of treatment . Subjects in both groups experienced significant decreases in pain and increases in shoulder function , but there was significantly more improvement in the manual therapy group compared to the exercise group . For example , pain in the manual therapy group was reduced from a pre-treatment mean ( ±SD ) of 6.7 ( ±0.3 ) to a post-treatment mean of 2.0 ( ±2.0 ) . In contrast , pain in the exercise group was reduced from a pre-treatment mean of 6.6 ( ±1.4 ) to a post-treatment mean of 3.0 ( ±1.8 ) . ROM at flexion , abduction and external rotation in the manual therapy group improved significantly while ROM in the exercise group did not . There were statistically differences among the groups in function ( P > 0.05 ) . Group 2 showed significantly greater improvements in the Neer Question naire score and shoulder satisfaction score than Group 1 . The patients treated with manual physical therapy applied by experienced physical therapists combined with supervised exercise in a brief clinical trial showed improvement of symptoms including increasing strength , decreasing pain and improving function earlier than with exercise program BACKGROUND DATA AND OBJECTIVE Although previous studies have evaluated the effect of different kinds of physical therapy in subacromial impingement syndrome ( SIS ) , there have been few investigations assessing the effectiveness of low-level laser therapy ( LLLT ) in shoulder disorders . The goal of this prospect i ve r and omized study was to assess whether gallium-arsenide ( Ga-As ) laser therapy improves the outcome of a comprehensive home exercise program in patients with SIS . MATERIAL S AND METHODS Forty-four newly-diagnosed SIS patients were enrolled in this study . Group 1 patients ( n = 22 ) received Ga-As laser therapy combined with a 12-wk comprehensive home exercise program , and group 2 patients ( n = 22 ) received the same 12-wk comprehensive home exercise program alone . Night pain , shoulder pain and disability index ( SPADI ) , and University of California-Los Angeles end- result ( UCLA ) scores were used as outcome measures . RESULTS Both groups showed a significant reduction in night pain and SPADI scores at the second and 12th weeks with respect to baseline values , with the exception of the SPADI total score at the second week in group 1 . UCLA results improved significantly in both groups at the 12th in comparison to the second week . There were no significant differences between groups in mean actual changes in night pain and SPADI scores at the second week from baseline . When values at the 12th week were compared to baseline , mean actual changes in night pain differed significantly between the groups , with a larger change in group 1 , but there was no difference between groups in mean actual change in SPADI scores . Second- and 12th-week UCLA scores did not differ between the two groups . CONCLUSION Our study was unable to demonstrate any distinct advantage of low-level laser therapy over exercise alone . Comprehensive home exercise programs should be the primary therapeutic option in the rehabilitation process in SIS STUDY DESIGN R and omized controlled trial . OBJECTIVE To evaluate the effects of an exercise protocol , with and without manual therapy , on scapular kinematics , function , pain , and mechanical sensitivity in individuals with shoulder impingement syndrome . BACKGROUND Stretching and strengthening exercises have been shown to effectively decrease pain and disability in individuals with shoulder impingement syndrome . There is still conflicting evidence regarding the efficacy of adding manual therapy to an exercise therapy regimen . METHODS Forty-six patients were assigned to 1 of 2 groups , one of which received a 4-week intervention of stretching and strengthening exercises ( exercise alone ) and the other the same intervention , supplemented by manual therapy targeting the shoulder and cervical spine ( exercise plus manual therapy ) . All outcomes were measured preintervention and postintervention at 4 weeks . Outcome measures were scapular kinematics in the scapular and sagittal planes during arm elevation , function as determined through the Disabilities of the Arm , Shoulder and H and ( DASH ) question naire , pain as assessed with a visual analog scale , and mechanical sensitivity as assessed with pressure pain threshold . RESULTS Independent of the intervention group , small , clinical ly irrelevant changes in scapular kinematics were observed postintervention . A significant group-by-time interaction effect ( P = .001 ) was found for scapular anterior tilt during elevation in the sagittal plane , with a 3.0 ° increase ( 95 % confidence interval [ CI ] : -1.5 ° , 7.5 ° ) relative to baseline in the exercise-plus-manual therapy group compared to a decrease of 0.3 ° ( 95 % CI : -4.2 ° , 4.8 ° ) in the exercise-alone group . Pain , mechanical sensitivity , and the DASH score improved similarly for both groups by the end of the intervention period . CONCLUSION Adding manual therapy to an exercise protocol did not enhance improvements in scapular kinematics , function , and pain in individuals with shoulder impingement syndrome . The noted improvements in pain and function are not likely explained by changes in scapular kinematics Acupuncture has gained increasing attention in the treatment of chronic pain . The lack of a satisfying placebo method has made it impossible to show whether needling is an important part of the method or whether the improvement felt by the patient is due to the therapeutic setting and psychological phenomena . Also , the effectiveness of acupuncture has not been demonstrated sufficiently . We treated 52 sportsmen with rotator cuff tendinitis in a r and omised single-blind clinical trial using a new placebo-needle as control . Patients were treated for 4 weeks . The primary endpoint of the trial was the change in the modified Constant-Murley-score from the baseline . Assessment of the treatment outcome was made by experienced orthopaedists not informed of the treatment allocation . Acupuncture with penetration of the skin was shown to be more effective than a similar therapeutic setting with placebo needling in the treatment of pain . The acupuncture-group improved 19.2 Constant-Murley-score points ( SD 16.1 , range from -13 to 50 ) , the control-group improved 8.37 points ( SD 14.56 , range from -20 to 41 ) , ( P=0.014 ; C.I. 2.3;19.4 ) . This study showed that needling is an important part of the acupuncture effect in the treatment of chronic shoulder pain in athletes . No conclusions can be derived from this study concerning the importance of choosing points and the rules of Traditional Chinese Medicine . Using the new placebo method as control for other ailments could improve the evidence of specific acupuncture effects beyond pain treatment OBJECTIVE To explore the effectiveness of naturopathic care ( NC ) on rotator cuff tendinitis using a prospect i ve r and omized clinical trial design . METHODS Canadian postal workers with rotator cuff tendinitis for a duration of > 6 weeks were r and omized to receive NC ( n = 43 ) or st and ardized physical exercises ( PEs ; n = 42 ) over 12 weeks . Participants in the NC group received dietary counseling , acupuncture , and Phlogenzym ( 2 tablets 3 times/day ) . The PE intervention group received passive , active-assisted , and active range of motion exercises and matched placebo . The primary outcome measure was the Shoulder Pain and Disability Index ( SPADI ) , and secondary outcomes were the pain visual analog scale ( VAS ) , Short Form 36 ( SF-36 ) , Measure Yourself Medical Outcomes Profile ( MYMOP ) , and shoulder maximal range of motion . Participants and assessors were blinded to group and placebo allocation . RESULTS Seventy-seven participants ( 87 % ) completed > or=8 weeks of the trial . Final total SPADI scores decreased by 54.5 % ( P < 0.0001 ) in the NC group and by 18 % ( P = 0.0241 ) in the PE group . Between-group differences in changes to SPADI scores showed statistically significant decreases in shoulder pain and disability in the NC group compared with the PE group ( P < 0.0001 ) . Significant differences between groups were also observed in the pain VAS , MYMOP , SF-36 , and shoulder extension , flexion , and abduction , with the NC group showing superiority in each outcome . No serious adverse reactions were observed . CONCLUSION NC and PE provided significant improvements , with greater improvement in shoulder function in the NC group compared with the PE group . Statistically significant improvements in quality of life measures were observed in the NC group as compared with the PE group Purpose To investigate superior value of adding heavy load eccentric training to conservative treatment in patients with subacromial impingement . Methods Sixty-one patients with subacromial impingement were included and r and omly allocated to the traditional rotator cuff training ( TT ) group ( n = 30 , mean age = 39.4 ± 13.1 years ) or traditional rotator training combined with heavy load eccentric training ( TT + ET ) group ( n = 31 , mean age = 40.2 ± 12.9 years ) . Isometric strength was measured to abduction at 0 ° , 45 ° and 90 ° of scapular abduction and to internal and external rotation . The SPADI question naire was used to measure shoulder pain and function . Patients rated subjective perception of improvement . Outcome was assessed at baseline , at 6 and 12 weeks after start of the intervention . Both groups received 9 physiotherapy treatments over 12 weeks . At home , the TT group performed traditional rotator cuff strengthening exercises 1x/day . The TT + ET group performed the same exercises 1x/day and a heavy load eccentric exercise 2x/day . Results After treatment , isometric strength had significantly increased in all directions , and SPADI score had significantly decreased . The TT + ET group showed a 15 % higher gain in abduction strength at 90 ° of scapular abduction . Chi-square tests showed patients ’ self-rated perception of improvement was similar in both groups . Conclusion Adding heavy load eccentric training result ed in a higher gain in isometric strength at 90 ° of scapular abduction , but was not superior for decreasing pain and improving shoulder function . This study showed that the combination of a limited amount of physiotherapy sessions combined with a daily home exercise programme is highly effective in patients with impingement . Level of evidence II |
1,695 | 11,115,167 | RESULTS Antipsoriatic effects of acitretin , cyclosporine , and psoralen-UV-A phototherapy were enhanced with the addition of topical calcipotriene using the Psoriasis Area and Severity Index as the outcome , but this is not translated into an increase in the number of patients who achieve at least marked improvement .
There is limited evidence that use of calcipotriene might reduce the cumulative exposure to phototherapy and systemic treatment .
Overall , there is insufficient evidence to support any large effects in favor of combination treatment .
In the patient assessment s , the results do not show an adjuvant effect , but there is some evidence that use of calcipotriene might reduce cumulative exposure to systemic therapy to obtain clearance .
There were no long-term morbidity data on the effectiveness of any of the combinations studied . | OBJECTIVE To examine the efficacy and tolerability of calcipotriene combined with phototherapy or systemic therapies compared with monotherapy for the treatment of chronic plaque psoriasis . | The synthetic compound MC 903 ( calcipotriol ) is a structural analogue of the naturally occurring , biologically active 1,25-dihydroxyvitamin D3 [ 1,25-(OH)2-D3 ] . MC 903 and 1,25-(OH)2-D3 show similar receptor binding and comparable effects on cell differentiation . However , MC 903 appears to be at least 100 times less potent in its effects on calcium metabolism . In previous double-blind placebo-controlled studies , topical MC 903 has been shown to have a therapeutic effect in psoriasis . The present open study involving 20 patients with psoriasis vulgaris was a right/left comparison of the efficacy and tolerability of MC 903 ointment ( 50 micrograms/g ) alone or with UVB radiation . After treatment for 8 weeks , topical MC 903 alone result ed in marked improvement in 66 % of the patients and in clearance in 17 % . Combination of topical MC 903 with UVB result ed in marked improvement in 50 % of the patients and in clearance in 39 % . These differences were not statistically significant . No significant change in serum calcium levels was detected . Two patients developed a facial dermatitis which disappeared spontaneously during continued treatment . These results show that the combination of topical MC 903 and UVB radiation is well tolerated . Larger-scale studies are warranted to answer the question whether UVB radiation induces a significant improvement of the antipsoriatic effect of topical MC 903 Summary Combining PUVA with other therapeutic agents which reduce the UVA dose required for clearance of psoriasis may be of benefit by reducing the long‐term risk of cutaneous malignancy and by increasing the efficacy of treatment . We have therefore studied the effect of calcipotriol in 13 patients with plaque‐type psoriasis who were about to start twice weekly PUVA . In each patient , from the start of PUVA treatment , two plaques on symmetrical body sites were selected for assessment . Calcipotriol ointment was applied to one twice daily , and placebo to the other . Response was assessed weekly for 6 weeks : an investigator , unaware of treatment allocation . compared psoriasis severity within each of the plaques , and blood flux was measured using a scanning laser‐Doppler velocimeter . Of the 11 patients who completed the study , in nine the calcipotriol‐treated plaque either cleared before the placebo‐treated plaque ( n=7 ) or was consistently judged to be better ( n = 2 ) . From the third week of the trial , mean blood flux was significantly lower in the calcipotriol‐treated plaques than in those treated with placebo . In the seven patients whose psoriasis was clear in at least one plaque at the end of the study period , there was a median reduction in UVA dose of 26·5 % for calcipotriol compared with placebo . With the exception of one patient , the improved response was not associated with earlier relapse BACKGROUND A narrow-b and UVB lamp ( Philips TL 01 ) emitting a peak of approximately 311 nm was developed to improve the phototherapy for psoriasis . Only a few studies have been performed with promising results . OBJECTIVE The therapeutic efficacy of the Philips TL 01 lamp in a new 100 W version was compared with conventional broad-b and lamps ( Sylvania UV 6 ) in a controlled trial . METHODS Twenty-three patients with psoriasis were treated with half-body exposures from the different UVB sources . The rate of clearing was monitored by estimation of the Psoriasis Area and Severity Index . All patients used emollients ; excessive scaling was removed with salicylic acid in yellow petrolatum . In 13 patients dithranol in a modified Ingram regimen was added . In most cases the study was discontinued once a difference between the two sides was evident . RESULTS In 20 of 23 cases the TL 01 lamp proved to be significantly more effective than the conventional source . Application of dithranol provided a substantial additional therapeutic effect . With the high-intensity TL 01/100W bulbs , exposure times were comparable to broad-b and UVB phototherapy . CONCLUSION The therapeutic efficacy of Philips TL 01/100W and its practicability for psoriasis phototherapy have been demonstrated BACKGROUND Recent advances in the treatment of psoriasis include both the topical vitamin D analogue calcipotriol and cyclosporine . Combined treatments have been sought to decrease the incidence of side effects while maintaining efficacy in the treatment of severe chronic plaque psoriasis . OBJECTIVE The objective of this study was to evaluate the efficacy and safety of the combination of 2 mg/kg/day of cyclosporine with calcipotriol ointment ( 50 micrograms/gm ) in the treatment of severe plaque psoriasis . METHODS Sixty-nine patients were r and omly selected for this double-blind , multicenter study to receive cyclosporine ( 2 mg/kg/day ) combined with calcipotriol ointment ( 50 micrograms/gm ) or cyclosporine ( 2 mg/kg/day ) combined with placebo ointment ( vehicle of calcipotriol ) for a 6-week period . RESULTS Complete clearing or 90 % improvement in Psoriasis Area and Severity Index score occurred in 50.0 % of patients in the calcipotriol/cyclosporine group in comparison with 11.8 % of patients treated with placebo/cyclosporine ( p = 0.0019 ) . The confidence interval for the difference ranged from 17.8 % to 58.7 % . No difference was found between the two groups with respect to side effects . CONCLUSION The calcipotriol/cyclosporine combination was more effective than placebo/cyclosporine . Further studies are needed to establish the long-term efficacy and safety profile of this combination therapy OBJECTIVE The aim of this study was to evaluate the efficacy and tolerability of the association of calcipotriol ointment ( 50 micrograms/g ) plus cyclosporine versus cyclosporine alone in the treatment of moderate psoriasis ( mean PASI : 13 ) . METHODS Twenty patients were enrolled in this right-left open study . All the patients admitted were treated with cylosporine at an initial dose of 4.5 mg/kg/day ; in case of clinical improvement this dosage was reduced by 0.5 mg/kg/day every 15 days . In each patient we chose two similar , symmetrical lesions and calcipotriol ointment was applied only on the right lesion , twice a day , until the healing of the lesion or for 1 month . Patients were checked at baseline and every 15 days . RESULTS Eighteen patients completed the study and 17 of the 18 presented more evident improvement on the side treated with combined therapy , while only one patient showed a better result on the side treated with cyclosporine alone . A significant difference of the total score was already present after 15 days of therapy and was confirmed at the following check-ups . CONCLUSIONS These results underline the usefulness of the association of calcipotriol and cyclosporine in order to decrease the total dosage of cyclosporine Ro 10 - 9359 is a retinoic acid derivative , selected for study because of a better tolerance than retinoic acid , shown in animal experiments . Doses of 25 mg b.i.d . , 25 mg t.i.d . and 50 mg b.i.d . were administered orally to 27 patients suffering from severe chronic generalized psoriasis . The clinical efficacy was evaluated by means of a new index , psoriasis area and severity index ( PASI ) based on severity and area of psoriatic lesions . At doses of 25 mg t.i.d . or 50 mg b.i.d . Ro 10 - -9359 proved to be an extremely potent antipsoriatic drug . A more than 90 % reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4 - 8 weeks of treatment . This good effect lasted about 5 weeks after treatment . Side effects were frequent , but mostly mild and completely reversible after termination of treatment Eighteen patients with symmetric plaque-type psoriasis were recruited for an open , controlled , bilateral half-body comparison study to evaluate the efficacy of calcipotriol/tar/UVB vs. anthralin/tar/UVB in a day care treatment setting . No patient had been on systemic antipsoriatic agents for at least 3 months prior to enrolment . One half-body was arbitrarily assigned to treatment with gradually increasing concentrations of anthralin as tolerated . The other half-body received calcipotriol ointment twice daily . Both sides received UVB and additional coal tar distillate in accordance with our st and ard day care regimen . Patients who were admitted to the day care program attended the clinic for UVB , anthralin , and calcipotriol on weekdays for two consecutive weeks . Anthralin was applied to psoriatic plaques on one side in the following fashion : anthralin 0.1 % with salicylic acid 3 % in zinc oxide paste on days 1 and 2 ; anthralin 0.2 % with salicylic acid 3 % in zinc oxide paste on days 3 - 5 ; anthralin 1 % with salicylic acid 3 % in hydrophilic petrolatum for 60 min on days 8 - 10 to thicker lesions ; and anthralin 2 % with salicylic acid 3 % in hydrophilic petrolatum for 60 min on day 11 to thicker lesions . On the contralateral side , calcipotriol ointment 0.05 microgram/mL ( Leo Pharmaceuticals , Ajax , Ontario ) was applied to lesions twice daily . No anthralin or calcipotriol was applied on weekends . All patients applied coal tar oil 50 % ( Doak Oil Forte , Trans CanaDerm , St-Laurent , Québec , equivalent to 5 % coal tar distillate ) with salicylic acid 5 % in hydrophilic petrolatum to their lesions at home in the evenings and on weekends . UVB ( FSX72T12 lamps , National Biologic Corporation , Twinsburg , Ohio ) was administered twice daily on weekdays in increasing doses as tolerated ( to erythema ) prior to the application of the topical medications . No trial medications were applied to the face , scalp , or genital regions . For clinical evaluation , the st and ard Psoriasis Activity and Severity Index ( PASI ) score was modified by splitting the score for area under 10 % ; the modified score ( mPASI ) for an area of coverage of 1%-4 % was 0.5 and for an area of 5%-9 % was 1 . The head and neck area was excluded from the analysis since neither anthralin nor calcipotriol was used at these sites . Each half-body was considered to represent 100 % in the area score determination . The maximum modified score for each side was 64.8 ( vs. 72 in the st and ard PASI scoring system ) . Clinical evaluations were completed at days 0 ( baseline ) , 3 , 7 , 10 , and 42 . The primary end-point was day 10 . On day 10 , patients were asked to compare the calcipotriol ointment to the anthralin on a five-point scale in terms of efficacy and irritancy and to state their future preferred treatment modality . Following discharge from day care , patients were continued on outpatient UVB and tar treatments three times weekly and asked to return for a repeat clinical assessment after 4 weeks ( day 42 ) . Blood sample s taken prior to treatment and at day 10 were analyzed for serum calcium . Comparisons of treatment efficacy were based on changes in the mPASI scores from onset of treatment to day 10 , as well as on the corresponding percentage changes . Analyses were carried out using the Wilcoxon test . Subjective patient comparisons of effectiveness and irritancy , as well as patient preference , were tested for equiprobability using the chi-square goodness-of-fit test with an examination of the adjusted residuals A total of 20 patients with symmetric plaque-type psoriasis were recruited for a controlled , investigator-blinded , right-left study . None of the patients had used any therapy other than emollients for 2 months prior to starting in the trial . All patients had a negative antinuclear antibody . By history , all patients had previously improved upon exposure to sunlight or ultraviolet light . Two symmetrical sites of equal severity were selected as target areas . Each patient was treated on one side with mineral oil twice daily and on the opposite side with calcipotriene 0.005 % ointment twice daily . The investigator was blinded as to which site received which topical treatment . Both sides were treated with equal doses of ultraviolet B ( UVB ) three times weekly in graduated suberythemogenic doses . Ultraviolet B radiation was emitted by a group of 6-ft fluorescent bulbs ( Light Sources FS72 T12 UVB HO ) in a st and ard phototherapy unit . The above regimen was continued for a total of 12 weeks . The severity of psoriasis in the target sites was rated by the examiner at baseline and at weekly intervals for the 12 weeks of study . Target sites were rated by severity of erythema , scaling , plaque elevation , and pruritus , with each of these parameters being assigned a score on a four-point scale : 0 , clear ; 1 , mild ; 2 , moderate ; 3 , severe . The four scores were added together to arrive at a total severity score for each of the target sites . Statistical analysis was performed using the paired t test , P values less than 0.05 were considered statistically significant . Eleven of the 20 patients ( 55 % ) showed a greater decrease in the severity of their psoriasis with UVB plus calcipotriene compared with UVB plus mineral oil . The difference in severity scores between the two groups was statistically significant as early as week 1 ( P < 0.05 ) . The difference between the UVB and calcipotriene group versus the UVB and mineral oil group peaked between weeks 3 and 6 . The differences then decreased but remained statistically significant through to week 12 ( Fig. 1 ) . There were no instances of local cutaneous irritation , but mild photosensitivity occurred symmetrically on both sides in three patients We studied the effects of combining topical calcipotriol , used at the maximal licensed dose , and narrow‐b and short wave ultraviolet light ( TL01 ) on systemic calcium homeostasis in the treatment of chronic plaque psoriasis . Patients were r and omized in an open fashion to receive either UVB alone , UVB plus 100 g of calcipotriol ( 50 μg/g ) ointment per week or calcipotriol ointment alone ( 100 g/week ) . With the exception of a slight increase in serum phosphate in the group receiving combination therapy ( from 0·92 to 1·22 mmol/l ; P= 0·046 ) , no differences were observed between or within the groups . Psoriasis area and severity scores ( PASI ) improved to a greater extent in those patients receiving both UVB and calcipotriol ( P= 0·045 ) . The combination of UVB and calcipotriol is a safe , effective treatment for chronic plaque psoriasis |
1,696 | 28,361,290 | The pooled effect estimate did not favor ATZ/r over DRV/r regarding the change in plasma levels of total cholesterol , triglycerides , or high-density lipoprotein at 24 , 48 , and 96 weeks .
The ATZ/r regimen was generally as effective and well-tolerated as the LPV/r regimen for the treatment of HIV-1 patients .
Compared to the DRV/r regimen , ATZ/r has no favorable effect on the plasma lipid profile or adipose tissue distribution | Atazanavir ( ATZ ) is a well-tolerated protease inhibitor that can be boosted with ritonavir ( r ) to treat infection with resistant strains of human immunodeficiency virus 1 ( HIV-1 ) .
The aim of this meta- analysis was to compare the efficacy , safety , and metabolic effects of ATZ/r regimen versus commonly used antiretroviral drugs such as lopinavir ( LPV ) and darunavir ( DRV ) in HIV-1-infected patients . | Objective : To evaluate atazanavir/ritonavir ( ATV/RTV ) ( 300/100 mg ) once daily , atazanavir/saquinavir ( ATV/SQV ) ( 400/1200 mg ) once daily , and lopinavir/ritonavir ( LPV/RTV ) ( 400/100 mg ) twice daily , each with tenofovir ( 300 mg ) once daily and a nucleoside reverse transcriptase inhibitor in treatment-experienced HIV-infected patients . Methods : R and omized , open-label , 48-week multicenter trial of 358 r and omized adult patients who had failed two or more prior HAART regimens with baseline HIV RNA ≥ 1000 copies/ml and CD4 cell count ≥ 50 × 106 cells/l . Results : The primary efficacy endpoint [ plasma HIV RNA reduction assessed by time-averaged difference ( TAD ) ] was similar for ATV/RTV and LPV/RTV [ TAD 0.13 ; 97.5 % confidence interval , −0.12 to 0.39 ] at 48 weeks . Mean reductions from baseline for ATV/RTV and LPV/RTV were comparable at 1.93 and 1.87 log10 copies/ml , respectively . Mean CD4 cell count increases were 110 and 121 × 106 cells/l for ATV/RTV , and LPV/RTV , respectively . The efficacy of ATV/SQV was lower than LPV/RTV by both these parameters . Declines in total cholesterol and fasting triglycerides were greater with ATV/RTV and ATV/SQV than with LPV/RTV ( P ≤ 0.005 ) . Lipids in the LPV/RTV arm at week 48 generally increased from baseline . Lipid-lowering agents were used more frequently in the LPV/RTV arm than in the ATV arms ( P < 0.05 versus ATV/RTV ) , as were antidiarrheal agents ( P ≤ 0.04 versus both ATV treatments ) . No new or unique safety findings emerged . Conclusions : ATV boosted with RTV is as effective and well tolerated as LPV/RTV in treatment-experienced patients , with a more favorable impact on serum lipids . Pharmacokinetically enhanced ATV provides a suitable choice for therapy of treatment-experienced HIV-infected patients BACKGROUND It is unclear whether metabolic or body composition effects differ between protease inhibitor-based regimens recommended for initial treatment of human immunodeficiency virus ( HIV ) infection . METHODS ATADAR is a phase 4 , open-label , multicenter , r and omized clinical trial . Stable antiretroviral-naive HIV-infected adults were r and omly assigned to atazanavir/ritonavir 300/100 mg or darunavir/ritonavir 800/100 mg in combination with tenofovir/emtricitabine daily . Predefined endpoints were treatment or virological failure , drug discontinuation due to adverse effects , and laboratory and body composition changes at 96 weeks . RESULTS At 96 weeks , 56 ( 62 % ) atazanavir/ritonavir and 62 ( 71 % ) darunavir/ritonavir patients remained free of treatment failure ( estimated difference 8.2 % ; 95 % confidence interval [ CI ] , -.6 to 21.6 ) and 71 ( 79 % ) atazanavir/ritonavir and 75 ( 85 % ) darunavir/ritonavir patients remained free of virological failure ( estimated difference 6.3 % ; 95 % CI , -.5 to 17.6 ) . Seven patients discontinued atazanavir/ritonavir and 5 discontinued darunavir/ritonavir due to adverse effects . Total and high-density lipoprotein cholesterol similarly increased in both arms , but there was a greater increase in triglycerides in the atazanavir/ritonavir arm . At 96 weeks , body fat ( estimated difference 2862.2 gr ; 95 % CI , 726.7 to 4997.7 ; P = .0090 ) , limb fat ( estimated difference 1403.3 gr ; 95 % CI , 388.4 to 2418.2 ; P = .0071 ) , and subcutaneous abdominal adipose tissue ( estimated difference 28.4 cm(2 ) ; 95 % CI , 1.9 to 55.0 ; P = .0362 ) increased more in the atazanavir/ritonavir arm than in darunavir/ritonavir arm . Body fat changes in the atazanavir/ritonavir arm were associated with higher insulin resistance . CONCLUSIONS We found no major differences between atazanavir/ritonavir and darunavir/ritonavir in efficacy , clinical ly relevant side effects , or plasma cholesterol fractions . However , atazanavir/ritonavir led to higher triglycerides and more total and subcutaneous fat than darunavir/ritonavir . Also , fat gains with atazanavir/ritonavir were associated with insulin resistance . Clinical Trials Registration . NCT01274780 BACKGROUND The use of either efavirenz or lopinavir-ritonavir plus two nucleoside reverse-transcriptase inhibitors ( NRTIs ) is recommended for initial therapy for patients with human immunodeficiency virus type 1 ( HIV-1 ) infection , but which of the two regimens has greater efficacy is not known . The alternative regimen of lopinavir-ritonavir plus efavirenz may prevent toxic effects associated with NRTIs . METHODS In an open-label study , we compared three regimens for initial therapy : efavirenz plus two NRTIs ( efavirenz group ) , lopinavir-ritonavir plus two NRTIs ( lopinavir-ritonavir group ) , and lopinavir-ritonavir plus efavirenz ( NRTI-sparing group ) . We r and omly assigned 757 patients with a median CD4 count of 191 cells per cubic millimeter and a median HIV-1 RNA level of 4.8 log10 copies per milliliter to the three groups . RESULTS At a median follow-up of 112 weeks , the time to virologic failure was longer in the efavirenz group than in the lopinavir-ritonavir group ( P=0.006 ) but was not significantly different in the NRTI-sparing group from the time in either of the other two groups . At week 96 , the proportion of patients with fewer than 50 copies of plasma HIV-1 RNA per milliliter was 89 % in the efavirenz group , 77 % in the lopinavir-ritonavir group , and 83 % in the NRTI-sparing group ( P=0.003 for the comparison between the efavirenz group and the lopinavir-ritonavir group ) . The groups did not differ significantly in the time to discontinuation because of toxic effects . At virologic failure , antiretroviral resistance mutations were more frequent in the NRTI-sparing group than in the other two groups . CONCLUSIONS Virologic failure was less likely in the efavirenz group than in the lopinavir-ritonavir group . The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance . ( Clinical Trials.gov number , NCT00050895 [ Clinical Trials.gov ] . ) BACKGROUND We assessed a once-daily combination to simplify therapy in patients infected with human immunodeficiency virus type 1 ( HIV-1 ) . METHODS A total of 355 adults with plasma HIV-1 RNA levels < 400 copies/mL were r and omly assigned to either switch to once-daily emtricitabine , didanosine , and efavirenz ( n=178 ) or maintain their protease inhibitor (PI)-based regimens ( n=177 ) . The primary end point was sustained suppression of plasma HIV-1 RNA levels to < 400 copies/mL. RESULTS At week 48 , the proportion of patients meeting the end point was 87.6 % in the PI group and 90.5 % in the once-daily group , with a treatment difference of -2.9 % ( upper bound of the 1-tailed 95 % confidence interval , 2.6 % ) . The proportion of patients with HIV-1 RNA levels < 50 copies/mL was higher in the once-daily group ( 87 % ) than in the PI group ( 79 % ) ( P<.05 ) . Resistance mutations to efavirenz and emtricitabine were detected in all patients in the once-daily group who experienced virologic failure while receiving study medication . The proportion of patients discontinuing study medication because of adverse events was similar between the once-daily group ( 9 % ) and the PI group ( 10 % ) ( P=.8 ) . CONCLUSIONS Substituting a convenient once-daily combination of emtricitabine , didanosine , and efavirenz for a PI-based regimen was well tolerated and associated with sustained virologic suppression Background : In BMS Study 045 , once-daily ( QD ) atazanavir/ritonavir ( ATV/RTV ) demonstrated comparable efficacy and safety to twice-daily ( BID ) lopinavir/ritonavir ( LPV/RTV ) over 48 weeks in treatment-experienced patients . Results of extended follow-up to 96 weeks are presented . Methods : BMS Study 045 was an open-label , r and omized , multi-national trial of HIV-infected patients with virologic failure on two or more prior HAART regimens design ed to evaluate the efficacy and safety of ATV/RTV ( 300/100 mg ) QD and LPV/RTV ( 400/100 mg ) BID , each with tenofovir ( 300 mg ) QD and one nucleoside reverse transcriptase inhibitor . The primary efficacy measure was the time-averaged difference ( TAD ) in reduction in HIV RNA from baseline . Secondary objectives included evaluation of safety and plasma lipid levels through week 96 . Results : Over 96 weeks , the ATV/RTV regimen demonstrated similar virologic efficacy to the LPV/RTV regimen . Mean reductions from baseline in HIV RNA were −2.29 and −2.08 log10 copies/ml , respectively [ TAD ( 97.5 % confidence interval ) : 0.14 log10 copies/ml ( −0.13 , 0.41 ) ] . The LPV/RTV regimen result ed in significant increases in total cholesterol ( + 9 % ) and fasting triglycerides ( + 30 % ) in comparison with the ATV/RTV regimen , which demonstrated decreases in these parameters [ −7 and −2 % , respectively , ( P < 0.0001 ) ] . Grade 2–4 diarrhoea occurred less frequently in ATV/RTV patients ( 3 % ) in comparison with LPV/RTV patients ( 13 % ) ( P < 0.01 ) . Grade 3–4 elevations in bilirubin were more common in ATV/RTV patients ( 53 % ) than LPV/RTV patients ( < 1 % ) ( P < 0.0001 ) , with no result ing discontinuations . Conclusions : Regimens containing once-daily ATV/RTV demonstrated comparable efficacy and safety , with significant reductions in total cholesterol and fasting triglycerides and improved gastrointestinal-tolerability in comparison with twice-daily regimens containing LPV/RTV over 96 weeks in treatment-experienced patients BACKGROUND Atazanavir/ritonavir is as effective as lopinavir/ritonavir , with a more favourable lipid profile and less gastrointestinal toxicity , in treatment-experienced HIV-1-infected patients . We compared these two combinations directly in treatment-naive patients . METHODS In this open-label , international non-inferiority study , 883 antiretroviral-naive , HIV-1-infected patients were r and omly assigned to receive atazanavir/ritonavir 300/100 mg once daily ( n=440 ) or lopinavir/ritonavir 400/100 mg twice daily ( n=443 ) , in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily . R and omisation was done with a computer-generated central ised r and omisation schedule and was stratified by baseline levels of HIV RNA ( viral load ) and geographic region . The primary endpoint was the proportion of patients with viral load less than 50 copies per mL at week 48 . The main efficacy analysis was done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00272779 . FINDINGS At week 48 , 343 ( 78 % ) of 440 patients receiving atazanavir/ritonavir and 338 ( 76 % ) of 443 patients receiving lopinavir/ritonavir had achieved a viral load of less than 50 copies per mL ( difference 1.7 % , 95 % CI -3.8 to 7.1 ) . Mean increases from baseline in CD4 cell count were similar ( 203 cells per muL in the atazanavir/ritonavir group vs 219 cells per muL in the lopinavir/ritonavir group ) . 25 ( 6 % ) patients in the atazanavir/ritonavir group and 26 ( 6 % ) in the lopinavir/ritonavir group were virological failures by week 48 . Only two patients , both in the atazanavir/ritonavir group , had non-polymorphic protease inhibitor resistance mutations emerge on treatment , which conferred phenotypic resistance to atazanavir in one patient . Serious adverse events were noted in 51 ( 12 % ) of 441 patients in the atazanavir/ritonavir group and in 42 ( 10 % ) of 437 patients in the lopinavir/ritonavir group . Fewer patients in the atazanavir/ritonavir group than in the lopinavir/ritonavir group experienced grade 2 - 4 treatment-related diarrhoea ( 10 [ 2 % ] vs 50 [ 11 % ] ) and nausea ( 17 [ 4 % ] vs 33 [ 8 % ] ) . Grade 2 - 4 jaundice was seen in 16 ( 4 % ) of 441 patients in the atazanavir/ritonavir group versus none of 437 patients in the lopinavir/ritonavir group ; grade 3 - 4 increases in total bilirubin were seen in 146 ( 34 % ) of 435 patients on atazanavir/ritonavir and in one ( < 1 % ) of 431 patients on lopinavir/ritonavir . INTERPRETATION In treatment-naive patients , atazanavir/ritonavir once-daily demonstrated similar antiviral efficacy to lopinavir/ritonavir twice-daily , with less gastrointestinal toxicity but with a higher rate of hyperbilirubinaemia OBJECTIVES To assess LDL subfraction phenotype and lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) in naive HIV-infected patients starting atazanavir/ritonavir or darunavir/ritonavir plus tenofovir/emtricitabine . METHODS This was a sub study of a multicentre r and omized study . St and ard lipid parameters , LDL subfraction phenotype ( by gradient gel electrophoresis ) and Lp-PLA2 activity ( by 2-thio-PAF ) were measured at baseline and weeks 24 and 48 . Multivariate regression analysis was performed . Results are expressed as the median ( IQR ) . RESULTS Eighty-six ( atazanavir/ritonavir , n=45 ; darunavir/ritonavir , n=41 ) patients were included : age 36 ( 31 - 41 ) years ; 89 % men ; CD4 319 ( 183 - 425 ) cells/mm(3 ) ; and Framingham score 1 % ( 0%-2 % ) . No differences in demographics or lipid measurements were found at baseline . At week 48 , a mild but significant increase in total cholesterol and HDL-cholesterol was observed in both arms , whereas LDL cholesterol increased only in the darunavir/ritonavir arm and triglycerides only in the atazanavir/ritonavir arm . The apolipoprotein A-I/apolipoprotein B ratio increased only in the atazanavir/ritonavir arm . At week 48 , the LDL subfraction phenotype improved in the darunavir/ritonavir arm ( increase in LDL particle size and in large LDL particles ) , whereas it worsened in the atazanavir/ritonavir arm ( increase in small and dense LDL particles , shift to a greater prevalence of phenotype B ) ; the worsening was related to the greater increase in triglycerides in the atazanavir/ritonavir arm . No changes in total Lp-PLA2 activity or relative distribution in LDL or HDL particles were found at week 48 in either arm . CONCLUSIONS In contrast with what occurred in the atazanavir/ritonavir arm , the LDL subfraction phenotype improved with darunavir/ritonavir at week 48 . This difference was associated with a lower impact on plasma triglycerides with darunavir/ritonavir Objectives : To evaluate the efficacy and safety of switching from boosted lopinavir ( LPV/r ) to boosted atazanavir ( ATV/r ) in virologically suppressed HIV-1-infected patients versus continuing LPV/r . Methods : Forty-eight weeks analysis of a r and omized , open-label , noninferiority trial including patients with virological suppression ( ≤200 copies/mL for ≥6 months ) on LPV/r-containing triple highly active antiretroviral therapy . Patients ( n = 248 ) were r and omized 1:1 either to continue LPV/r twice a day ( n = 127 ) or to switch to ATV/r every day ( ATV/r ; n = 121 ) , with no change in nucleoside reverse transcriptase inhibitor backbone . Those known to have > 4 protease inhibitor (PI)-associated mutations and /or who had failed > 2 PI-containing regimens were excluded . Results : Baseline characteristics were balanced . 30 % harboured ≥1 PI-associated mutation ( 10 % harboured ≥1 major mutation ) . Treatment failure at 48 weeks ( primary end point ) occurred in 20 % ( 25 of 127 ) of the LPV/r arm and in 17 % ( 21 of 121 ) of the ATV/r arm ( difference −2.3 % ; 95 % confidence interval : −12.0 to 8.0 ; P = 0.0018 ) . Virological failure occurred in 7 % ( 9 of 127 ) of the LPV/r arm and in 5 % ( 6 of 121 ) of the ATV/r arm ( difference −2.1 % ; 95 % confidence interval : −8.7 % to 4.2 % , P < 0.0001 for noninferiorating ) . CD4 + changes from baseline were similar in each arm ( approximately 40 cells/mm3 ) . Adverse event rate leading to study drug discontinuation was 5 % in both arms . Median fasting triglycerides and total cholesterol decreased significantly in the ATV/r arm ( −53 and −19 mg/dL , respectively versus −4 and −4 mg/dL in the LPV/r arm ; P < 0.001 in both comparisons ) . Alanine aminotransferase/aspartate aminotransferase hepatic abnormalities were similar in the 2 arms . Conclusions : Switching to ATV/r in virologically suppressed patients who were receiving a LPV/r-containing highly active antiretroviral therapy provided comparable ( noninferior ) efficacy and a safety profile with improved lipid parameters [ IS RCT N24813210 ] Background : Once-daily atazanavir/ritonavir demonstrated similar antiviral efficacy to twice-daily lopinavir/ritonavir over 48 weeks , with less gastrointestinal disturbance and a better lipid profile , in treatment-naive patients . Methods : International , multicenter , open-label , 96-week noninferiority r and omized trial of atazanavir/ritonavir 300/100 mg once daily vs lopinavir/ritonavir 400/100 mg twice daily , each in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily , in antiretroviral-naive , HIV-1-infected patients . The primary end point was the proportion of patients with HIV RNA < 50 copies/mL at 48 weeks . Results through 96 weeks are reported . Results : Of 883 patients enrolled , 440 were r and omized to atazanavir/ritonavir and 443 to lopinavir/ritonavir . At week 96 , more patients receiving atazanavir/ritonavir achieved HIV RNA < 50 copies/mL ( 74 % vs 68 % , P < 0.05 ) in the intent-to-treat analysis . On both regimens , 7 % of subjects were virologic failures by 96 weeks . Bilirubin-associated disorders were greater in patients taking atazanavir/ritonavir . Treatment-related gastrointestinal adverse events were greater in patients taking lopinavir/ritonavir . Mean changes from baseline in fasting total cholesterol , non-high-density lipoprotein cholesterol , and triglycerides at week 96 were significantly higher with lopinavir/ritonavir ( P < 0.0001 ) . Conclusions : Noninferiority of atazanavir/ritonavir to lopinavir/ritonavir was confirmed at 96 weeks . Atazanavir/ritonavir had a better lipid profile and fewer gastrointestinal adverse events than lopinavir/ritonavir Background : Few r and omized clinical trials have investigated antiretroviral regimens in very advanced HIV-1–infected patients . The objective was to study the immune reconstitution in very immunosuppressed antiretroviral-naive , HIV-1–infected individuals by comparing an efavirenz-based regimen with 2 ritonavir-boosted protease inhibitor regimens . Methods : R and omized , controlled , open-label , multicenter clinical trial . Eighty-nine HIV-1–infected antiretroviral-naive patients with < 100 CD4 cells per cubic millimeter were r and omly assigned in a 1:1:1 ratio to efavirenz ( n = 29 ) , atazanavir/ritonavir ( n = 30 ) , or lopinavir/ritonavir ( n = 30 ) combined with tenofovir plus emtricitabine . The primary outcome was median increase in CD4 cell count at week 48 . Secondary end points were the proportion of patients with HIV-1 RNA < 50 copies per milliliter , adverse events , disease progression , and death . Results : In the on-treatment analysis , the median ( interquartile range ) increase in the CD4 count after 48 weeks was + 193 ( 129–349 ) cells per microliter in the efavirenz arm , + 197 ( 146–238 ) cells per microliter in the ritonavir-boosted atazanavir arm , and + 205 ( 178–327 ) cells per microliter in the ritonavir-boosted lopinavir arm ( P = 0.73 ) . The percentage of patients achieving viral suppression was similar in all 3 treatment arms at 48 weeks { efavirenz , 85.71 % [ 95 % confidence interval ( CI ) : 68.5 to 94.3 ] ; atazanavir , 80 % [ 95 % CI : 62.7 to 90.5 ] ; and lopinavir , 82.8 % [ 95 % CI : 65.5 to 92.4 ] ; P = 0.88}. Bacterial translocation , inflammation , immune activation , and apoptotic markers , but not D-dimer , declined significantly and similarly in the 3 treatment arms . Adverse events had a similar incidence in all 3 antiretroviral regimens . No patients died . Conclusions : The immune reconstitution induced by an efavirenz-based regimen in very advanced HIV-1–infected patients was similar to that induced by a ritonavir-boosted protease inhibitor – based regimen ( Clinical Trials.gov registration number : NCT00532168 ) BACKGROUND Once-daily combination therapy with emtricitabine , didanosine and efavirenz has been highly effective in clinical trials but its long-term efficacy and safety has not been previously reported . METHODS This multicentre , single-arm , open-label trial enrolled 40 antiretroviral-naive HIV-1-infected patients who received a once-daily regimen of emtricitabine , didanosine and efavirenz . The objective was to assess the long-term effects of this combination on plasma HIV RNA levels , CD4 + T-cell counts , safety and tolerability . RESULTS After 5 years , 73 % and 68 % of patients had plasma HIV RNA levels < 400 and < 50 copies/ml , respectively , in an intent-to-treat , missing-equals-failure analysis . Genotypic resistance on treatment emerged in six patients . There was a significant increase in CD4 + T-cell count of 294 x 10(6 ) cells/l . Only six patients discontinued study treatment , because of non-severe adverse events . Lipodystrophy was infrequent , and lipid and glucose profiles were favourable with a significant increase in high-density lipoprotein cholesterol . CONCLUSION A convenient once-daily regimen of emtricitabine , didanosine and efavirenz provided durable antiretroviral response and was well tolerated through 5 years of therapy Objective : To compare the efficiency and safety of atazanavir and nelfinavir in antiretroviral-naive patients . Design : R and omization to atazanavir 400 mg or 600 mg once daily ; nelfinavir 1250 mg twice a day , plus lamivudine and stavudine . Methods : A blinded ( to the atazanavir dose ) , 48-week trial in patients with HIV-1 RNA ⩾ 2000 copies/ml , CD4 cell count ⩾ 100 × 106cells/l . Primary end-point : change in HIV-1 RNA from baseline at 48 weeks . Secondary end-point : subjects with HIV-1 RNA < 400 , and < 50 copies/ml , CD4 cell count changes , adverse events . Results : The 467 r and omized subjects had comparable baseline characteristics across treatments . With atazanavir 400 mg , 600 mg and nelfinavir , respectively , mean changes in HIV-1 RNA ( log10 copies/ml ) from baseline to 48 weeks were −2.51 , −2.58 , −2.31 ; HIV-1 RNA < 400 copies/ml [ intent-to-treat population ( ITT ) , non-completion = failure ( NC = F ) ] , 64 % , 67 % , 53 % ; HIV-1 RNA < 50 copies/ml ( ITT NC = F ) , 35 % , 36 % , 34 % ; mean CD4 cell count increased comparably at 48 weeks ( 234 × 106 , 243 × 106 , 211 × 106cells/l ) . Adverse events were similar across treatments with the exception of diarrhea ( more frequent with nelfinavir ) and jaundice ( more frequent with atazanavir ) . Mean changes from baseline to 48 weeks were : fasting low density lipoprotein cholesterol , + 5.2 % , + 7.1 % and + 23.2 % ( at 56 weeks ) and fasting triglycerides ( 48 weeks ) , + 7.2 % , + 7.6 % and + 49.5 % , in the atazanavir 400 mg , 600 mg , and nelfinavir groups , respectively ( P < 0.01 , atazanavir versus nelfinavir ) . Conclusions : Atazanavir is a potent , safe , well tolerated , and effective once-daily protease inhibitor with low pill burden ( two capsules/day ) . Lipid changes with atazanavir were significantly less than with nelfinavir , however , clinical significance of these finding in terms of decreased cardiovascular risk is unknown The introduction of combination antiretroviral therapy for HIV infection revolutionized treatment of AIDS and HIV disease . Such treatment , which usually includes two nucleoside analogue inhibitors of HIV reverse transcriptase and at least one HIV protease inhibitor or non-nucleoside inhibitor of HIV reverse transcriptase , is called highly active antiretroviral therapy ( HAART ) . Early cohort and registry-based studies showed a lower incidence of AIDS and decreased rates of AIDS-related mortality after the introduction of HAART in late 1995 in the United States ( 1 - 3 ) , France ( 4 ) , Australia ( 5 ) , Germany ( 6 ) , and Switzerl and ( 7 ) . However , ecologic studies those that measured use of HAART and mortality in groups rather than in individual patients may be subject to confounding by calendar period changes in other unmeasured variables . In addition , many studies that directly measured the effects of HAART on survival of patients with AIDS did not provide specific evidence of such effects in the patients with the most advanced cases ( 8 - 10 ) , with the exception of small cohorts of patients with cytomegalovirus ( CMV ) retinitis ( 11 ) and progressive multifocal leukoencephalopathy ( 12 ) . We therefore studied the effect of HAART in a large multicenter trial of blood transfusion in patients with advanced HIV disease who were also anemic , an indicator of poor prognosis ( 13 , 14 ) . Because the study spanned the period before and after the introduction of HAART , we could directly assess the effect of HAART status on subsequent death or opportunistic events . In addition , because our person-year analysis was controlled for calendar time , our estimates of the magnitude of the effect of HAART on mortality and morbidity are less likely to be confounded by changes in patient mix or medical practice compared with previously published studies . Methods Patients and Study Design The Viral Activation Transfusion Study ( VATS ) was a multicenter , r and omized , double-blind clinical trial of leukoreduced versus nonleukoreduced red blood cell transfusion in HIV-infected patients who required a first transfusion for anemia . Details of the study design have been published elsewhere ( 15 , 16 ) . In brief , we enrolled patients who were HIV seropositive , were CMV seropositive or had a history of documented CMV disease , had an expected survival of at least 1 month , and required red blood cell transfusion for anemia . Data on clinical end points and prescribed medications were obtained by interview and medical record review at baseline and every 3 months thereafter . Ophthalmologic examinations to detect CMV retinitis were done at baseline and every 6 months thereafter . In patients who did not return for follow-up visits , vital status was ascertained by review of the medical record , a search for a death certificate , and tracing by using public data bases . Of 528 patients , 58 were excluded before death or end of the study , including 29 for whom no follow-up information on opportunistic events was available and 3 for whom follow-up for death but not for opportunistic events was complete . The CD4 + lymphocyte count and plasma HIV RNA level were measured by using frozen blood specimens at the central study laboratory , as described elsewhere ( 15 ) . The study protocol was approved by the institutional review boards of the 11 participating medical centers , and informed consent was obtained from all participants . Definitions of HAART and End Points The VATS did not dictate the choice of antiretroviral therapy for enrolled patients , except that prescription of new antiretroviral drugs was discouraged during the 2 weeks after the first two transfusion episodes . Highly active antiretroviral therapy was defined as prescription of at least three antiretroviral medications with activity against HIV , at least one of which was an HIV protease inhibitor or a non-nucleoside HIV reverse transcriptase inhibitor . Medication history collected at each quarterly visit included the names and start and stop date s of any HIV antiretroviral medications taken since the previous visit or in the 30 days before entry into the study . Patients taking no HIV antiretroviral medications and those taking HIV antiretroviral medications that did not fulfill our definition of HAART were classified as before HAART until the day that they began HAART . Once a patient initiated HAART , all of his or her subsequent follow-up time remained design ated as after HAART even if they discontinued HAART , to approximate an intention-to-treat analysis . We made this conservative decision to avoid overestimating the effect of HAART , which would occur if patients who stopped HAART because of intolerance subsequently contributed outcomes to the before HAART person-years . Adherence to prescribed medications was not measured . End points of the current study were death , opportunistic events , and recurrent transfusions . Opportunistic events were defined a priori and confirmed by expert review ers ; they included clinical diagnoses corresponding to the Centers for Disease Control and Prevention 's AIDS-defining conditions ( 17 ) , with some modifications . Presumptive diagnoses of central nervous system toxoplasmosis were allowed according to the Centers for Disease Control and Prevention 's definition . For CMV retinitis , progression of disease requiring initiation of or a change in anti-CMV medication counted as a clinical event . For analysis , end points were grouped as follows : CMV opportunistic events ; non-CMV opportunistic events ; all opportunistic events ; death ; and any end point , including death and all opportunistic events . We analyzed recurrent red blood cell transfusion ( that is , occurring after the enrollment transfusion event ) as a separate end point . Statistical Analysis We used a person-years approach to analyze event rates . The denominator for these rates was not the individual patient but was person-years of observation time , defined as study follow-up time for each patient classified as before or after initiation of HAART and summed over all patients . For example , patients who started HAART during the study contributed observation time to both the post-HAART and pre-HAART categories , in effect serving as their own controls . Patients who began HAART before study entry and those who never began HAART during the study period contributed only post-HAART or pre-HAART observation time , respectively . Observation time for a patient extended from the date of study entry to death or the end of follow-up . Because some patients had no follow-up information for opportunistic events and a few had less follow-up for opportunistic events than for mortality , the total observation time for opportunistic events was shorter than that for overall survival . Events were assigned to the time period during which they occurred , and incidence was reported as the number of events per person-year of observation time . A single patient could contribute multiple events ( except for the mortality analysis ) to the same or to different time periods . The association between HAART use and incidence rates was expressed as a rate ratio . Confidence intervals and P values were calculated from a Poisson regression model using generalized estimating equations with exchangeable correlation structure to adjust for correlated observations across time within the same patient ( 18 , 19 ) . All P values are two sided . Because the use of HAART increased dramatically over the 4 years of the study , the comparison of post-HAART and pre-HAART data is confounded with calendar time . In addition , the mixture of HIV risk groups , prevalence of prophylaxis against opportunistic infections , diagnostic testing accuracy , and physician experience may have changed over time . To evaluate and control for these and other calendar time effects , each patient 's observation time was further categorized as four 1-year calendar time periods , starting in July 1995 . Similarly , a patient 's time since entering the study was divided into five study time periods ( 0 to 6 , 7 to 12 , 13 to 18 , 19 to 24 , or > 24 months from r and omization ) . The Poisson regression generalized estimating equations method was then used to calculate the rate ratios associated with CD4 T-cell count , plasma HIV RNA level , calendar time , and time on study and to adjust the comparisons of post-HAART and pre-HAART data for these covariates , both in pairs and combined with patient characteristics . Results Participants The VATS enrolled patients with anemia and HIV infection who received a first red blood cell transfusion between August 1995 and July 1998 . Patients were followed until death or their last scheduled quarterly visit before 30 June 1999 . Of 531 patients enrolled in VATS , we excluded 3 patients for whom no data on medication were available ; thus , the sample for analysis in this study was 528 patients . Table 1 shows the baseline characteristics of the study sample . Most patients were 30 to 49 years of age and male , and equal proportions of patients were of white and nonwhite ethnicity . Half of the patients were men who reported sex with other men as their only HIV risk factor ; 19 % each were injection drug users or sexually active heterosexuals without other risk factors for HIV ; and 12 % had multiple or other risk factors . At baseline , the median CD4 + lymphocyte count was 0.015 109 cells/L , and 69 % of patients had a CD4 + lymphocyte count less than 0.050 109 cells/L. The median HIV RNA level was 4.8 log10 copies/mL , and only 8 % of patients had plasma levels of HIV RNA levels less than 200 copies/mL. Table 1 . Baseline Characteristics of 528 Patients in the Viral Activation Transfusion Study At baseline , most patients had previously taken antiretroviral medication ; more than half had taken such medication for 12 months or longer . The proportion of patients taking prophylaxis or treatment of Pneumocystis carinii pneumonia and Mycobacterium avium complex infection decreased from 95 % and 49 % , respectively , in 19951996 to 82 % and 44 % in Abstract Background : The objective of this study was to compare the efficacy of ritonavir boosted atazanavir versus ritonavir boosted lopinavir or efavirenz , all in combination with 2 nucleoside analogue reverse transcriptase inhibitors ( NRTIs ) , over 144 weeks in antiretroviral-naïve HIV-1-infected individuals . Methods : A prospect i ve open-label r and omized controlled trial was conducted at 29 sites in Sweden and Norway between April 2004 and December 2009 . Patients were r and omized to receive either efavirenz 600 mg once daily ( EFV ) , or atazanavir 300 mg and ritonavir 100 mg once daily ( AZV/r ) , or lopinavir 400 mg and ritonavir 100 mg twice daily ( LPV/r ) . The primary endpoints were the proportion of patients with HIV-1 RNA < 50 copies/ml at 48 and 144 weeks . Results : Of 245 patients enrolled , 243 were r and omized and 239 received the allocated intervention : 77 EFV , 81 AZV/r , and 81 LPV/r . Median ( interquartile range ) CD4 cell counts at baseline were 150 ( 80–200 ) , 170 ( 80–220 ) , and 150 ( 90–216 ) per microlitre , respectively . At week 48 the proportion ( 95 % confidence interval ( CI ) ) of patients achieving HIV-1 RNA < 50 copies/ml was 86 (78–94)% in the EFV arm , 78 (69–87)% in the AZV/r arm and , 69 (59–78)% in the LPV/r arm in the intention-to-treat analysis . There was a significant difference between the EFV and LPV/r arm ( p = 0.014 ) . At week 144 , the proportion ( 95 % CI ) of patients achieving HIV-1 RNA < 50 copies/ml was 61 (50–72)% , 58 (47–69)% , 51 (41–63)% , respectively ( p = 0.8 ) . Patients with CD4 cell counts of ≤ 200/μl or HIV-1 RNA > 100,000 copies/ml at baseline had similar response rates in all arms . Conclusion : EFV was superior to LPV/r at week 48 , but there were no significant differences between the 3 arms in the long-term ( 144 weeks ) follow-up |
1,697 | 26,873,043 | For complication outcomes that did include at least 2 studies in the meta- analysis , there was no clear evidence to support a difference between eEVAR and open repair .
Outcomes between eEVAR and open repair , specifically 30-day mortality , are similar . | OBJECTIVES Emergency endovascular aneurysm repair ( eEVAR ) may improve outcomes for patients with ruptured abdominal aortic aneurysm ( RAAA ) .
The study aim was to compare the outcomes for eEVAR with conventional open surgical repair for the treatment of RAAA . | OBJECTIVE To assess the efficacy of endovascular aneurysm repair ( EVAR ) against st and ard alternative management in patients with large abdominal aortic aneurysm ( AAA ) . DESIGN Two national , multicentre r and omised trials - EVAR trials 1 and 2 . SETTING Patients were recruited from 38 out of 41 eligible UK hospitals . PARTICIPANTS Men and women aged at least 60 years , with an AAA measuring at least 5.5 cm on a computerised tomography scan that was regarded as anatomically suitable for EVAR , were assessed for fitness for open repair . Patients considered fit were r and omised to EVAR or open repair in EVAR trial 1 and patients considered unfit were r and omised to EVAR or no intervention in EVAR trial 2 . INTERVENTIONS EVAR , open repair or no intervention . MAIN OUTCOME MEASURES The primary outcome was mortality ( operative , all-cause and AAA related ) . Patients were flagged at the UK Office for National Statistics with central ly coded death certificates assessed by an Endpoints Committee . Power calculations based upon mortality indicated that 900 and 280 patients were required for EVAR trials 1 and 2 , respectively . Secondary outcomes were graft-related complications and re interventions , adverse events , renal function , health-related quality of life and costs . Cost-effectiveness analyses were performed for both trials . RESULTS Recruitment occurred between 1 September 1999 and 31 August 2004 , with targets exceeded in both trials : 1252 r and omised into EVAR trial 1 ( 626 to EVAR ) and 404 r and omised into EVAR trial 2 ( 197 to EVAR ) . Follow-up closed in December 2009 with very little loss to follow-up ( 1 % ) . In EVAR trial 1 , 30-day operative mortalities were 1.8 % and 4.3 % in the EVAR and open-repair groups , respectively : adjusted odds ratio 0.39 [ 95 % confidence interval ( CI ) 0.18 to 0.87 ] , p = 0.02 . During a total of 6904 person-years of follow-up , 524 deaths occurred ( 76 AAA related ) . Overall , there was no significant difference between the groups in terms of all-cause mortality : adjusted hazard ratio ( HR ) 1.03 ( 95 % CI 0.86 to 1.23 ) , p = 0.72 . The EVAR group did demonstrate an early advantage in terms of AAA-related mortality , which was sustained for the first few years , but lost by the end of the study , primarily due to fatal endograft ruptures : adjusted HR 0.92 ( 95 % CI 0.57 to 1.49 ) , p = 0.73 . The EVAR procedure was more expensive than open repair ( mean difference £ 1177 ) and not found to be cost-effective , but the model was sensitive to alternative assumptions . In EVAR trial 2 , during a total of 1413 person-years of follow-up , a total of 305 deaths occurred ( 78 AAA related ) . The 30-day operative mortality was 7.3 % in the EVAR group . However , this group later demonstrated a significant advantage in terms of AAA-related mortality , but this became apparent only after 4 years : overall adjusted HR 0.53 ( 95 % CI 0.32 to 0.89 ) , p = 0.02 . Sadly , this advantage did not result in any benefit in terms of all-cause mortality : adjusted HR 0.99 ( 95 % CI 0.78 to 1.27 ) , p = 0.97 . Overall , EVAR was more expensive than no intervention ( mean difference £ 10,222 ) and not found to be cost-effective . CONCLUSIONS EVAR offers a clear operative mortality benefit over open repair in patients fit for both procedures , but this early benefit is not translated into a long-term survival advantage . Among patients unfit for open repair , EVAR is associated with a significant long-term reduction in AAA-related mortality but this does not appear to influence all-cause mortality . TRIAL REGISTRATION Current Controlled Trials IS RCT N 55703451 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 16 , No. 9 . See the HTA programme website for further project information The modern era of aortic aneurysm repair started in AAA 4.0 - 5.5 cm in diameter . 5 The U.K Small AnEurope . The first successful resection of an abdominal eurysm Trial Participants were 126 vascular surgeons aortic aneurysm , with homograft replacement , was from 93 hospitals who collaborated in a r and omised performed in Paris on 25th March , 1951 , by Dubost trial to collect the evidence to answer the question : and colleagues , t Homografts were rapidly replaced does early elective surgery or ultrasound surveillance by prosthetic grafts of man-made fibres . Since then provide the better management for patmnts with small prostheses have been developed and st and ardised , AAA ? the operative techniques refined and anaesthesia has In the 4-year period between Autumn 1991 and improved . The number of aneurysms repaired electAutumn 1995 , 1090 patients , aged 60 - 76 years , were lvely each year continues to rise , with procedures m r and omised to a treatment policy of either early electEngl and and Wales having almost doubled recently , i ve surgery ( n=563 ) or a period of ultrasound surfrom 1405 to 2378 in the five years from 1990 - 1995 . 2 velllance ( n = 527 ) . Ultrasound surveillance was Few have stopped to consider to what extent the continued at regular intervals untd the anaurysm diapatmnt benefits from elective surgical repair of an meter exceeded 5.5 cm , the aneurysm became tender , abdominal aortic aneurysm . Since the start of ultraor the aneurysm grew by > 1 cm in a year . The trial sound screening programmes m the 1980s , more and protocol , together with details of how the trial was more asymptomatic abdominal aortic aneurysms executed , have been published previously in this ( AAAs ) are being detected . 3 Most of these screenjournal . 5 detected AAAs are small , < 5.5 cm in diameter . Should The end points of the UK Small Aneurysm Trial such aneurysms be repaired electlvely ? The first evlwere : all cause mortahty ; aneurysm related mortality ; dence to answer this question comes from Europe . quality of life ; costs and cost-effectiveness . The U K. Small Aneurysm Trial reported at the Annual An independent Data Monitoring and Ethics CornMeeting of the Vascular Surgical Society of Great Britmlttee review ed the progress of the trial after each ain and Irel and in November 1998 . 4 The evidence , successive 70 deaths and was empowered to stop the outlined below , indicates that elective open surgical trial at any point , should either one treatment arm repair of an asymptomatic AAA of < 5.5 cm in diameter be clearly superior or the 30-day operative mortahty should not be recommended , exceed 5 % ( allowing for appropriate confidence inThe U.K. Small Aneurysm Trial was established m tervals ) . The trial participants and Trial Steering Com1991 because many vascular surgeons in Britain were mittee were blind to all results until after the trial uncertain whether elective surgical aneurysm repair closed on 30th June , ] 998 . At this time the mean patient should be offered to patients with small asymptomatic follow-up was 4.6 years and 309 deaths had been recorded . At r and omisatlon , the baseline characteristics of the 563 patients r and omised to early elective surgery and Please address all correspondence to l T Powell , Imperial College School of Medicine , Charmg Cross Hospital , Fulham Palace Road , the 527 patients r and omised to ultrasound surveillance London W6 8RF , U K were very similar . The mean age of the surgery INTRODUCTION EVAR has the potential to improve outcome after ruptured abdominal aortic aneurysm ( AAA ) . Published series have been based upon selected population s. METHODS An interim analysis of a single centre prospect i ve r and omised controlled trial comparing endovascular aneurysm repair ( EVAR ) with open aneurysm repair ( OAR ) in patients with ruptured AAA was performed . Patients who had a ruptured AAA and who were considered fit for open repair were r and omised to EVAR or OAR after consent had been obtained . Those in the EVAR group had pre-operative spiral computed tomographic angiography ( CTA ) . The primary endpoint was operative ( 30-day ) mortality and secondary endpoints were moderate or severe operative complications , hospital stay and time between diagnosis and operation . A power study calculation required 100 patients to be recruited . RESULTS Between September 2002 and December 2004 , 103 patients were admitted with suspected ruptured AAA . Only 32 patients were recruited to the study . Of these , four patients died before receiving surgical treatment . On an intention to treat basis the 30-day mortality rate was 53 % in the EVAR group and 53 % in the OAR group . Moderate or severe operative complications occurred in 77 % in the EVAR group and in 80 % in the OAR group . Median total hospital stay in the EVAR group was 10 days ( inter-quartile range 6 - 28 ) and 12 days ( 4 - 52 ) in the OAR group . Median time between diagnosis and operation was 75 minutes ( 64 - 126 ) in the EVAR group and 100 minutes ( 48 - 138 ) in the OAR group . CONCLUSIONS Despite the relative high operative mortality in the EVAR group , these preliminary results show that it is possible to recruit patients to a r and omised trial of OAR and EVAR in patients with ruptured AAA . CT scanning does not delay treatment The objective of the Amsterdam Acute Aneurysm Trial is to study the combined outcome of conventional emergency surgery versus endovascular treatment for ruptured abdominal aortic aneurysms . The design used was a multicenter r and omized clinical trial conducted in two university hospitals and one teaching hospital in the Amsterdam region . The study included all patients with a ruptured abdominal aneurysm who were eligible for endovascular and conventional surgery . The primary end points were combined mortality and severe morbidity . The secondary end points were quality of life and cost-effectiveness . The background , design , and methods of this trial are presented , and the ethical and legal issues of this type of research are discussed INTRODUCTION acute haemodynamic changes and /or loss of abdominal muscle tone can occur during induction of general anaesthesia and may be the Achilles ' tendon in endovascular aneurysm repair ( EVAR ) of ruptured aortoiliac aneurysms ( rAIA ) . The purpose of this study was to evaluate the use of local anaesthesia ( LA ) for EVAR to overcome these limitations . METHODS twenty-one consecutive patients with rAIA are included in this study . Twenty patients underwent EVAR under LA , and 1 patient was treated under general anaesthesia . Haemodynamics were stabilised during assessment of EVAR feasibility by CT-scan and during the procedure itself by controlled hypotension ( MAP 50 - 60 mmHg ) and moderate fluid resuscitation . RESULTS median procedure time was 120 min . Haemodynamics remained stable in all but 3 patients who required transfemoral balloon occlusion of the supra-renal aorta . Perioperative intubation was necessary in 5 patients because of respiratory distress ( n=3 ) , or retroperitoneal access ( n=2 ) . Temporary deterioration of renal function occurred in 6 patients , with 2 requiring hemofiltration . CT-scan confirmed sealing of the rAIA in all patients at discharge . 30-day mortality was 9.5 % ( 2 deaths ) . In the median follow-up of 19 months , there were no deaths , but 3 endovascularre- interventions , 1 crossover femoro-femoral bypass , and 1 open surgical graft repair . DISCUSSION our series is the first to show that EVAR for rAIA can be safely performed under LA . This approach allows implantation of commercially available bifurcated SG and improves patient outcome BACKGROUND Although endovascular aneurysm repair ( EVAR ) has a lower 30-day operative mortality than open repair , the long-term results of EVAR are uncertain . We instigated EVAR trial 1 to compare these two treatments in terms of mortality , durability , health-related quality of life ( HRQL ) , and costs for patients with large abdominal aortic aneurysm ( AAA ) . METHODS We did a r and omised controlled trial of 1082 patients aged 60 years or older who had aneurysms of at least 5.5 cm in diameter and who had been referred to one of 34 hospitals proficient in the EVAR technique . We assigned patients who were anatomically suitable for EVAR and fit for an open repair to EVAR ( n=543 ) or open repair ( n=539 ) . Our primary endpoint was all-cause mortality , with secondary endpoints of aneurysm related mortality , HRQL , postoperative complications , and hospital costs . Analyses were by intention to treat . FINDINGS 94 % ( 1017 of 1082 ) of patients complied with their allocated treatment and 209 died by the end of follow-up on Dec 31 , 2004 ( 53 of aneurysm-related causes ) . 4 years after r and omisation , all-cause mortality was similar in the two groups ( about 28 % ; hazard ratio 0.90 , 95 % CI 0.69 - 1.18 , p=0.46 ) , although there was a persistent reduction in aneurysm-related deaths in the EVAR group ( 4%vs 7 % ; 0.55 , 0.31 - 0.96 , p=0.04 ) . The proportion of patients with postoperative complications within 4 years of r and omisation was 41 % in the EVAR group and 9 % in the open repair group ( 4.9 , 3.5 - 6.8 , p<0.0001 ) . After 12 months there was negligible difference in HRQL between the two groups . The mean hospital costs per patient up to 4 years were UK pound sterling 13,257 for the EVAR group versus pound sterling 9946 for the open repair group ( mean difference pound sterling 3311 , SE 690 ) . INTERPRETATION Compared with open repair , EVAR offers no advantage with respect to all-cause mortality and HRQL , is more expensive , and leads to a greater number of complications and re interventions . However , it does result in a 3 % better aneurysm-related survival . The continuing need for interventions m and ates ongoing surveillance and longer follow-up of EVAR for detailed cost-effectiveness assessment Endovascular aortic repair ( EVAR ) treatment for ruptured aortoiliac aneurysms ( rAIA ) avoids the additional surgical insult to physiology that comes with laparotomy and open repair ( OR ) . In systematic review s , the pooled mortality rate from rAIA after EVAR is around 20 % and morbidity around 40 % . The proportion of patients with rAIA treated by EVAR is steadily increasing , as most centers are adopting an EVAR as a first line therapy . However , two trials , one r and omized ( n = 32 ) and one nonr and omized , failed to demonstrate any benefit of EVAR to OR . The multicentric r and omized study named ECAR ( for Endosvasculaire vs Chirurgie dans les Anévrysmes Rompus ) was setup on 160 patients to compare the EVAR vs OR in rAIA . The primary outcome is mortality at 1 month . The study started in January 2008 and is still in progress BACKGROUND Organ failure is a major cause of morbidity and mortality after abdominal aortic aneurysm ( AAA ) repair . The aim of this study was to determine the relationships between the systemic inflammatory response syndrome ( SIRS ) , organ failure , and mortality after AAA repair and to determine whether the clinical monitoring of SIRS was a useful adjunct to clinical method . METHODS One hundred consecutive patients undergoing open AAA repair were prospect ively studied . Patients were divided into three groups : those undergoing elective AAA repair , those with symptomatic but nonruptured AAA , and those with ruptured AAA . The presence of SIRS and organ failure was recorded on a daily basis for each patient until discharge or death . RESULTS Most patients had SIRS develop during the postoperative period : 89 % of the elective group , 92 % of the emergency nonruptured ( urgent ) group , and 100 % of the ruptured group . Multiorgan failure occurred in 3.8 % of the elective group , 38 % of the urgent group , and 64 % of the ruptured AAA group . After ruptured AAA repair , the concurrent absence of both SIRS and any organ failure for 48 hours had a sensitivity of 93 % and a specificity of 91 % as a predictive indicator of subsequent survival to hospital discharge . Patients in whom multiorgan failure developed after ruptured AAA repair had a significantly higher mortality rate ( 69 % ) than those who did not ( 0 % ; P = .001 ; 95 % CI for the difference , 30.2 % to 85.8 % ) . CONCLUSION The differences in the incidence rate of multiorgan failure between the patient groups compared with the high incidence rate of SIRS in all patient groups supports the two-hit hypothesis of multiorgan failure . The presence of multiorgan failure after ruptured AAA repair is associated with poor outcome . The absence of SIRS and organ failure in these patients is a good predictive indicator of survival OBJECTIVE To assess whether a strategy of endovascular repair ( if aortic morphology is suitable , open repair if not ) versus open repair reduces early mortality for patients with suspected ruptured abdominal aortic aneurysm . DESIGN R and omised controlled trial . SETTING 30 vascular centres ( 29 UK , 1 Canadian ) , 2009 - 13 . PARTICIPANTS 613 eligible patients ( 480 men ) with a clinical diagnosis of ruptured aneurysm . INTERVENTIONS 316 patients were r and omised to the endovascular strategy ( 275 confirmed ruptures , 174 anatomically suitable for endovascular repair ) and 297 to open repair ( 261 confirmed ruptures ) . MAIN OUTCOME MEASURES 30 day mortality , with 24 hour and in-hospital mortality , costs , and time and place of discharge as secondary outcomes . RESULTS 30 day mortality was 35.4 % ( 112/316 ) in the endovascular strategy group and 37.4 % ( 111/297 ) in the open repair group : odds ratio 0.92 ( 95 % confidence interval 0.66 to 1.28 ; P=0.62 ) ; odds ratio after adjustment for age , sex , and Hardman index 0.94 ( 0.67 to 1.33 ) . Women may benefit more than men ( interaction test P=0.02 ) from the endovascular strategy : odds ratio 0.44 ( 0.22 to 0.91 ) versus 1.18 ( 0.80 to 1.75 ) . 30 day mortality for patients with confirmed rupture was 36.4 % ( 100/275 ) in the endovascular strategy group and 40.6 % ( 106/261 ) in the open repair group ( P=0.31 ) . More patients in the endovascular strategy than in the open repair group were discharged directly to home ( 189/201 ( 94 % ) v 141/183 ( 77 % ) ; P<0.001 ) . Average 30 day costs were similar between the r and omised groups , with an incremental cost saving for the endovascular strategy versus open repair of £ 1186 ( € 1420 ; $ 1939 ) ( 95 % confidence interval -£625 to £ 2997 ) . CONCLUSIONS A strategy of endovascular repair was not associated with significant reduction in either 30 day mortality or cost . Longer term cost effectiveness evaluations are needed to assess the full effects of the endovascular strategy in both men and women . TRIAL REGISTRATION Current Controlled Trials IS RCT N48334791 BACKGROUND Opposing views have been published on the importance of ultrasound screening for abdominal aortic aneurysms . The Multicentre Aneurysm Screening Study was design ed to assess whether or not such screening is beneficial . METHODS A population -based sample of men ( n=67800 ) aged 65 - 74 years was enrolled , and each individual r and omly allocated to either receive an invitation for an abdominal ultrasound scan ( invited group , n=33839 ) or not ( control group , n=33961 ) . Men in whom abdominal aortic aneurysms ( > or =3 cm in diameter ) were detected were followed-up with repeat ultrasound scans for a mean of 4.1 years . Surgery was considered on specific criteria ( diameter > or = 5.5 cm , expansion > or = 1 cm per year , symptoms ) . Mortality data were obtained from the Office of National Statistics , and an intention-to-treat analysis was based on cause of death . Quality of life was assessed with four st and ardised scales . The primary outcome measure was mortality related to abdominal aortic aneurysm . FINDINGS 27147 of 33839 ( 80 % ) men in the invited group accepted the invitation to screening , and 1333 aneurysms were detected . There were 65 aneurysm-related deaths ( absolute risk 0.19 % ) in the invited group , and 113 ( 0.33 % ) in the control group ( risk reduction 42 % , 95 % CI 22 - 58 ; p=0.0002 ) , with a 53 % reduction ( 95 % CI 30 - 64 ) in those who attended screening . 30-day mortality was 6 % ( 24 of 414 ) after elective surgery for an aneurysm , and 37 % ( 30 of 81 ) after emergency surgery . INTERPRETATION Our results provide reliable evidence of benefit from screening for abdominal aortic aneurysms AIM Several studies have shown the feasibility of endovascular repair of ruptured abdominal aortic aneurysms ( rEVAR ) . However , the role and value of rEVAR remains controversial due to selection bias and lack of long-term results . In the present study we describe our short- and long-term results of treating patients with rEVAR irrespective of hemodynamic condition and challenging anatomy . METHODS In April 2006 we started the single centre prospect i ve non-r and omised Ruptured Aneurysm Study ( RASA ) . During a four year enrolment period all consecutive patients presenting with infrarenal ruptured AAA ( rAAA , N.=117 ) were assessed for preferential rEVAR treatment . A rAAA was defined as extravasation of blood or hematoma outside the AAA due to transmural tear in the infrarenal abdominal aorta wall documented by preoperative computed tomography ( CT ) angiography examination or during open repair . Patients with challenging anatomy ( infrarenal neck length below 15 mm and neck angulation above 60 degrees ) were included as part of a damage control concept . Complication and mortality rates were studied at 30 days and yearly afterwards . RESULTS Thirty-five patients ( 33 % of all admitted rAAA ) were treated with rEVAR and 42 % of them were considered hemodynamically unstable ( systolic blood pressure < 100 mmHg ) and 30 % had challenging AAA anatomy . The mortality rate at 30 days in the rEVAR group was 17 % , in the open repair group 31 % , and in the entire rAAA group ( including abstained patients ) 36 % . During the first 30 days , 18 rEVAR patients experienced complications with nine re- interventions as a result . Long-term mortality of the rEVAR patients was 34 % after a median follow-up of 3.4 years . All deaths after one year follow-up were non-AAA related . Multivariate analysis shows that Hardman index , presence of peripheral arterial obstructive disease and lowest systolic blood pressure during surgery are independently associated with long-term survival . Challenging rAAA anatomy was not associated with impaired survival . CONCLUSION Our study shows that rEVAR is feasible irrespective of hemodynamic condition and that it is associated with relative low mortality rates . Challenging rAAA anatomy may not affect overall long-term survival , but six out of ten patients remain unsuitable for rEVAR because of inappropriate anatomy PURPOSE To report our experience in establishing a treatment protocol for endovascular aneurysm repair ( EVAR ) of ruptured abdominal aortic aneurysms ( rAAA ) , including an investigation of the reasons for patient exclusion and a report of our short-term results . METHODS Between 1997 and July 2002 , 21 patients with rAAA underwent endovascular repair according to our protocol and were followed prospect ively . A retrospective analysis was also conducted of 23 rAAA patients treated with open repair from January 2001 through June 2002 . Procedural and clinical data from this sample were compared to 14 contemporaneous emergent EVAR cases and analyzed to determine why the open repair patients were not treated with an endovascular approach . RESULTS Among the 21 patients treated with emergent EVAR since the beginning of this protocol , 6 ( 29 % ) procedures were performed under local anesthesia and 6 were performed percutaneously . Thirty-day mortality was 19 % . In the comparison of 14 emergent EVAR cases to 23 open rAAA repairs , the mean duration of symptoms prior to intervention was 12 hours for the EVAR patients and < 1 hour for OR patients . No significant difference was found in operating time , but the EVAR group had significantly less blood loss ( p=0.0001 ) and transfusion needs ( p=0.02 ) ; duration of intensive care unit stay was significantly shorter in the EVAR group ( p=0.02 ) . Thirty-day mortality was 29 % ( 4/14 ) for EVAR and 35 % for OR ( 8/23 ) ( p>0.05 ) . Reasons for not performing EVAR were unavailability of adequate equipment ( n=11 ) or trained staff ( n=7 ) , hemodynamically unstable patient ( n=2 ) , mycotic aneurysm ( n=2 ) , and unfavorable anatomy in a 60-year old patient with a < 5-mm-long , sharply angled infrarenal neck . CONCLUSIONS Endovascular repair of ruptured aortic aneurysms is feasible , and short-term results are promising . Good logistics , adequate training of physicians and staff in an elective setting , and versatile endografts are prerequisites for this type of treatment program OBJECTIVE Outcome of treatment of patients with ruptured or symptomatic non-ruptured aneurysm ( rAAA and snrAAA ) , preferentially treated by emergency endovascular repair was assessed . The outcome was compared with a historical group of patients treated by open repair . PATIENTS AND METHODS Two groups of patients presenting with acute symptomatic AAA were compared . Group I ( study group ) consisted of 40 consecutive prospect ively enrolled patients from May 2001 until June 2002 , in whom emergency endovascular abdominal aortic aneurysm repair ( e-EVAR ) was the preferential management . Short or wide neck or profound hypovolemic shock were exclusion criteria for e-EVAR . Group II ( control group ) consisted of 28 patients , retrospectively analysed , all treated by conventional surgical repair between January 1999 and May 2001 . In group I , 26 patients had rAAA and in group II 22 patients . The other patients had snrAAA . RESULTS In group I , 14 patients were treated by open repair . Unsuitable anatomy or profound hypovolemia was the cause of open repair in eight patients , while logistic reasons were the reasons for use of open repair in six patients ( off- protocol use of open surgery ) . Thus , in this prospect i ve series the feasibility of EVAR was 80 % ( 32/40 ) . Patient characteristics , proportion rAAA or hemodynamically unstable patients were comparable in group I and II . Volume of blood loss and need for fluid transfusion were significantly less in group I compared to group II . The perioperative mortality in group I was significantly less than in group II ( 20 % vs. 43 % , respectively , p = 0.04 ) . If patients with rAAA were considered the mortality was 31 % in group I and 50 % in group II , which difference did not reach the level of statistical significance . CONCLUSION e-EVAR was a feasible treatment in the majority of patients with rAAA and snrAAA . Blood loss and the requirements of fluid transfusion were significantly decreased . Most importantly in this institutional series significantly lower first-month mortality was observed in the group with preferential e-EVAR compared to a control group . A multi-center study assessing the outcome of preferential use of e-EVAR in patients with acute symptomatic AAA is required OBJECTIVE The objective of this study was to examine patterns of referral , management , and outcome of patients with ruptured abdominal aortic aneurysm ( RAAA ) within the catchment area of this regional vascular unit ( RVU ) . METHODS Referral , management , and outcome data regarding 972 consecutive patients admitted to the hospital or certified deceased in the community because of RAAA between January 1 , 1989 , and December 31 , 1995 , were retrieved from prospect ively gathered computerized national and local data bases . RESULTS Of 381 ( 39.2 % ) patients admitted to this unit , 316 ( 82.9 % ) underwent surgery , and of those , 188 ( 59.5 % ) survived . There was no significant difference in overall mortality between patients who were admitted directly to this unit ( 152 of 310 , 49 % ) and those who were transferred from elsewhere ( 41 of 71 , 58 % ) . Surgical patients traveled significantly farther to the RVU than nonsurgical patients ( P < .001 ) , but there was no significant difference in traveling distance between surgical patients who survived and those who did not . Of 372 ( 38 % ) patients who were admitted to other units and not transferred , 24 ( 6.4 % ) underwent surgery and 14 ( 3.8 % ) survived . Of 972 patients , the overall community mortality from RAAA was 770 ( 79 % ) . CONCLUSION Transferring patients from outlying units did not appear to prejudice operative outcome in this RVU . However , less than half of all RAAA patients were transferred , and only a small minority of those not transferred underwent surgery . Although the overall community mortality from RAAA was similar to that reported in earlier studies from other regions and countries where central ization has not occurred , central ization of vascular surgical services may be associated with an inappropriately low operation and survival rate for those patients who are not transferred to the regional center . The effect of central ization on the community outcome of emergent vascular surgical conditions requires further investigation BACKGROUND Endovascular aneurysm repair ( EVAR ) to exclude abdominal aortic aneurysm ( AAA ) was introduced for patients of poor health status considered unfit for major surgery . We instigated EVAR trial 2 to identify whether EVAR improves survival compared with no intervention in patients unfit for open repair of aortic aneurysm . METHODS We did a r and omised controlled trial of 338 patients aged 60 years or older who had aneurysms of at least 5.5 cm in diameter and who had been referred to one of 31 hospitals in the UK . We assigned patients to receive either EVAR ( n=166 ) or no intervention ( n=172 ) . Our primary endpoint was all-cause mortality , with secondary endpoints of aneurysm-related mortality , health-related quality of life ( HRQL ) , postoperative complications , and hospital costs . Analyses were by intention to treat . FINDINGS 197 patients underwent aneurysm repair ( 47 assigned no intervention ) and 80 % of patients adhered to protocol . The 30-day operative mortality in the EVAR group was 9 % ( 13 of 150 , 95 % CI 5 - 15 ) and the no intervention group had a rupture rate of 9.0 per 100 person years ( 95 % CI 6.0 - 13.5 ) . By end of follow up 142 patients had died , 42 of aneurysm-related factors ; overall mortality after 4 years was 64 % . There was no significant difference between the EVAR group and the no intervention group for all-cause mortality ( hazard ratio 1.21 , 95 % CI 0.87 - 1.69 , p=0.25 ) . There was no difference in aneurysm-related mortality . The mean hospital costs per patient over 4 years were UK pound sterling 13,632 in the EVAR group and pound sterling 4983 in the no intervention group ( mean difference pound sterling 8649 , SE 1248 ) , with no difference in HRQL scores . INTERPRETATION EVAR had a considerable 30-day operative mortality in patients already unfit for open repair of their aneurysm . EVAR did not improve survival over no intervention and was associated with a need for continued surveillance and re interventions , at substantially increased cost . Ongoing follow-up and improved fitness of these patients is a priority BACKGROUND Endovascular aneurysm repair ( EVAR ) is a new technology to treat patients with abdominal aortic aneurysm ( AAA ) when the anatomy is suitable . Uncertainty exists about how endovascular repair compares with conventional open surgery . EVAR trial 1 was instigated to compare these treatments in patients judged fit for open AAA repair . METHODS Between 1999 and 2003 , 1082 elective ( non-emergency ) patients were r and omised to receive either EVAR ( n=543 ) or open AAA repair ( n=539 ) . Patients aged at least 60 years with aneurysms of diameter 5.5 cm or more , who were fit enough for open surgical repair ( anaesthetically and medically well enough for the procedure ) , were recruited for the study at 41 British hospitals proficient in the EVAR technique . The primary outcome measure is all-cause mortality and these results will be released in 2005 . The primary analysis presented here is operative mortality by intention to treat and a secondary analysis was done in per- protocol patients . FINDINGS Patients ( 983 men , 99 women ) had a mean age of 74 years ( SD 6 ) and mean AAA diameter of 6.5 cm ( SD 1 ) . 1047 ( 97 % ) patients underwent AAA repair and 1008 ( 93 % ) received their allocated treatment . 30-day mortality in the EVAR group was 1.7 % ( 9/531 ) versus 4.7 % ( 24/516 ) in the open repair group ( odds ratio 0.35 [ 95 % CI 0.16 - 0.77 ] , p=0.009 ) . By per- protocol analysis , 30-day mortality for EVAR was 1.6 % ( 8/512 ) versus 4.6 % ( 23/496 ) for open repair ( 0.33 [ 0.15 - 0.74 ] , p=0.007 ) . Secondary interventions were more common in patients allocated EVAR ( 9.8 % vs 5.8 % , p=0.02 ) . INTERPRETATION In patients with large AAAs , treatment by EVAR reduced the 30-day operative mortality by two-thirds compared with open repair . Any change in clinical practice should await durability and longer term results An ultrasonography screening programme for detecting abdominal aortic aneurysm ( AAA ) in the community is described in which 7200 men and women aged between 65 and 80 years were contacted by letter . Of these , 4237 were screened ; the aorta was visualized in 4122 and 179 AAAs of 3 cm or more in diameter were detected ( 4.3 per cent ) . Criteria for surgery are suggested and the results of their application prospect ively over 6 years are discussed . Using these criteria , under 10 per cent of patients with ultrasonographically‐detected AAA should require surgery for this condition provided ultrasonography follow‐up is used OBJECTIVES To assess the mid-term outcomes up to 5 years following endovascular repair of abdominal aortic aneurysms ( EVAR ) , following its initial introduction into practice in the UK . DESIGN A prospect i ve voluntary Registry of Endovascular Treatment of Aneurysms ( RETA ) collected demographic and risk factor data , short term ( 30 day ) outcomes and follow up outcomes up to 5 years from the 41 centres that initially undertook EVAR in the UK . RESULTS Short term outcomes ( 30 days ) : 90.4 % of aneurysms were successfully excluded , 6.1 % had persistent endoleaks and 5.8 % of patients had died . Follow up was obtained from 30 days up to 5 years ( mean 3.1 years ) . Returns rates for requested follow up data were 87 % at 1 year and 77 , 65 , 52 and 51 % at 2 , 3 , 4 and 5 years , respectively . Ninety percent of deaths at follow up were unrelated to the stent-graft or aneurysm . Persistent proximal type I endoleak was associated with significant mortality both from attempted open repair or from rupture if untreated . Other endoleaks were more benign . Complications related to the aneurysm or device occurred at an average rate of 15 % per annum . The most common complications were secondary endoleaks or graft migration . Endovascular treatment was preferred if treatment was necessary for graft complications . The cumulative freedom from secondary procedure ( Kaplan-Meier ) were 87 , 77 , 70 , 65 and 62 % at 1 , 2 , 3 , 4 and 5 years of follow up , respectively . CONCLUSIONS Registry data provides useful information to guide the design of more formal trials . Collecting follow up from voluntarily su bmi tted data is difficult . The registry data remains well ahead of the trial data , but indicate that long term follow up is required in these trials , because of the high rate of complications seen at follow up PURPOSE To evaluate anatomical suitability and application rate for endovascular repair of patients with a ruptured abdominal aortic aneurysm ( RAAA ) . METHODS The Amsterdam Acute Aneurysm trial is a multicenter r and omised trial comparing open with endovascular treatment in patients with a RAAA ( International St and ard R and omized Controlled Trial Number ( IS RCT N ) 66212637 ) . Between April 2004 and January 2006 , all consecutive patients with clinical suspicion of a RAAA at presentation were assessed prospect ively . Anatomical suitability for endovascular repair was based on use of an aorto-uni-iliac endovascular graft and assessed in patients with a proven aortic rupture on CT angiography ( CTA ) . RESULTS In 128/256 patients , presenting with clinical suspicion of a ruptured aneurysm , RAAA was diagnosed . 105 patients were brought to a trial center and CTA confirmed RAAA in 83 patients . In 38 of 83 patients ( 45.8 % ) with positive CTA , the anatomy of the aorta and iliac arteries was considered suitable for endovascular repair . Exclusion from endovascular repair was due to unsuitable infrarenal neck or iliac anatomy ( 37 and 8 patients respectively ) . Overall , endovascular treatment was applicable in 38/128 patients ( 29.7 % ) with a RAAA in the Amsterdam region and in 38 out of 105 patients ( 35.5 % ) admitted to the trial centers . CONCLUSION In this prospect i ve cohort of all patients with a RAAA in the Amsterdam Acute Aneurysm Trial region , the suitability for endovascular repair in patients with a RAAA confirmed on CTA is 45.8 % , but the application rate was lower Abstract Background : Systematic review s have suggested a survival advantage for patients with ruptured abdominal aortic aneurysm ( AAA ) , who are managed by endovascular repair . These review s are based on single centre experiences of selected patients . Objective : To determine whether a policy of endovascular repair improves the survival of all patients with ruptured AAA . Methods : A r and omized controlled trial , IMPROVE ( IS RCT N 48334791 ) will r and omize patients with a clinical diagnosis of rAAA , made in hospital , either to immediate CT scan and endovascular repair whenever anatomically suitable ( endovascular first ) , or to open repair , with CT scan being optional ( normal care ) , The trial is set on a background of guidelines for emergency care , CT scanning and anaesthesia , which incorporate the protocol of permissive hypotension . Recruitment started in October 2009 and 600 patients are required to show a 14 % survival benefit at 30 days ( primary outcome ) for the endovascular first policy . Recruitment will be from the UK and Europe . Secondary outcomes include 24h , in-hospital and 1 year survival , complications , major morbidities , costs and quality of life . Discussion : This is a “ real life ” trial that will answer the fundamental relevant clinical dilemma , namely , do patients who present with ruptured AAA derive benefit from treatment in a system , which offers a preferential strategy of endovascular repair ? The trial addresses whether the anticipated reduced mortality and morbidity associated with endovascular repair is offset by the relatively greater ease of access and speed to conventional surgery . This issue is pivotal to future patient care and provision of services |
1,698 | 11,034,673 | The lack of evidence of benefit in long term survival does not support the routine or selective use of glycerol treatment in patients with acute stroke | BACKGROUND Brain oedema is a major cause of early death after stroke .
A 10 % solution of glycerol is a hyperosmolar agent that is cl aim ed to reduce brain oedema .
OBJECTIVES To determine whether I.V. glycerol treatment in acute stroke , either ischaemic or haemorrhagic , influences death rates and functional outcome in the short or long term and whether the treatment is safe . | A double-blind , r and omized trial was performed with 51 patients suffering from focal ischemic lesions in the territory of the middle cerebral artery . Intravenous infusions of 10 % glycerol in 0.9 % NaCI - 5 % glucose solutions were administered twice daily for 6 days to 26 patients , and the same amount of NaCI - glucose solutions to 25 controls . Glycerol did not reduce mortality ( 9 deaths in each group ) . The functional recovery was assessed by repeated neurological examinations during the 4 month trial . Glycerol significantly improved global performances and motor and sensory functions in patients with moderate disability , but its effect on global performances was transient . The patients with severe disability were not improved at all Abstract A double-blind evaluation of the effects of glycerol administration intravenously for 4 or 6 days in patients with acute stroke was completed in a stroke centre . Fifty-four patients with acute cerebral infa rct ion and eight patients with spontaneous intracerebral haemorrhage were admitted to the study . The neurological status was evaluated by use of a neurological scoring system . Patients with cerebral infa rct ion treated with glycerol showed significant improvement in neurological status compared to the patients treated with placebo ( The effects of intravenous glycerol and intravenous dextrose were compared using a double-blind trial in twenty-seven patients with acute stroke . Administration continued for up to 6 days . A st and ard scoring system was used for neurological evaluation . There was no difference in mortality or in improvement in neurological score between the two groups The results of clinical trials investigating various therapies in acute ischemic stroke have been inconsistent . The effect of glycerol therapy and a combination therapy of glycerol and dextran was evaluated in a double-blind , placebo-controlled study . Repeated neurologic examinations ( Day 0 , Weeks 1 , 6 , 12 , and 24 ) according to a modified Mathew score were performed on 62 patients . Statistical analysis showed no superiority of either treatment compared with placebo in acute ischemic stroke . A retrospective estimation of the Type II error of the study yielded approximately p = 0.25 . A major side effect was hemolysis in 98 % of patients treated with glycerol 1 . In patients with acute strokes entering a large ongoing r and omised double-blind controlled trial of intravenous glycerol therapy , the extent and pathogenesis of any ensuing haemolysis were evaluated using st and ard clinical investigations and in vitro techniques . 2 . Twenty patients received 10 % glycerol in saline ( 500 ml over 4 h on 6 consecutive days ) and 15 received corresponding control treatment with saline . 3 . Intravascular haemolysis was evident after the first infusion ; compared with the controls the glycerol group had i ) a greater mean reduction in serum haptoglobin concentration ( P less than .05 ) , and ii ) a greater proportion exhibiting haemoglobinaemia ( P = 0.03 ) . 4 . After 6 days of glycerol treatment , the mean reduction in haemoglobin concentration was only 0.8 g more than in controls ; this difference being neither clinical ly nor statistically significant . 5 . Glycerol therapy was not associated with haemoglobinuria , renal insufficiency or disseminated intravascular coagulation . 6 . Exposure of red blood cells to 1 - 10 % glycerol in vitro did not induce haemolysis per se ; on re-exposure to lower concentrations lysis ensued provided a minimum osmotic gradient was present . 7 . Whilst taking st and ard dosage regimes of glycerol , the stroke patients we studied manifested a degree of intravascular haemolysis but its consequences were not clinical ly significant ; lysis probably ensued after venous blood acquiring high glycerol concentrations mixed with blood containing little or no glycerol Background and Purpose This clinical trial investigates the effectiveness of intravenous glycerol therapy in patients with acute cortical infa rct ion in whom intracerebral hemorrhage was rigorously excluded . Methods Within 48 hours of symptoms from their first ischemic stroke , 113 hospital in patients were r and omized into the trial , provided that hemorrhage was excluded by computed tomography and informed consent was obtained . Patients were stratified into alert , semicoma , and coma groups using the Glasgow Coma Scale . Treatment was allocated according to a double-blind , r and omized protocol ; 56 patients received 500 mL of 10 % glycerol in saline over 4 hours on 6 consecutive days , and 57 patients received corresponding placebo treatment with saline . Using a variety of objective scoring systems , patient follow-up was up to 6 months . Results Corresponding measures of outcome in the glycerol and placebo groups were similar . At 6 months , respective mortality rates were 17 of 56 and 16 of 57 , and mean ±SD improvements in scores were 9.98±14.40 vs 10.51±12.68 ( long-term ) , 1.12±7.20 vs 1.57±6.30 ( prognostic ) , −1.94±5.53 vs −2.06±5.34 ( Glasgow Coma Scale ) , and 21.72±23.40 vs 11.94± 18.10 ( Barthel Index rating in survivors ) . Hemolysis ( generally sub clinical ) was the only adverse effect . Conclusions There was no clinical ly or statistically significant difference in outcome between the groups ; a trend toward greater functional recovery among survivors was evident after treatment with glycerol A prospect i ve study of 93 acute stroke patients r and omly selected by type of antiedema treatment given ( hypertonic glicerol infusion plus dexamethasone versus dexamethasone alone ) failed to elicit any statistically significant difference between the two treatments on survival rates and quality of survival 7 and 30 days after the stroke Intravenous administration of glycerol has been used in an effort to improve the prognosis for patients with acute cerebral infa rct ion . Fifty patients were treated actively and 56 served as a control group . The neurological status before , during and after treatment for six days was assessed by a score system . The patients were grouped according to the initial score . Those with the highest and lowest scores did not improve from glycerol infusion . However , the treated patients with intermediate scores , where the prognosis is known to be dubious , showed a significant improvement compared to the controls . The mortality was not influenced . No undesirable side-effects from glycerol were registered Background and Purpose Hitherto , treatment of acute cerebral hemorrhage with intravenous glycerol has not been evaluated in rigorous clinical studies with sufficient patient numbers . Methods We undertook a double-blind , stratified and r and omized , placebo-controlled clinical trial . Only patients with a first stroke admitted to the hospital within 24 hours after onset of symptoms were recruited , provided computed tomography confirmed hemorrhage and informed consent was obtained . After stratification into alert , semicoma , and coma subgroups using the Glasgow Coma Scale , 107 patients received active treatment ( 500 ml of 10 % glycerol in saline by intravenous infusion over 4 hours on 6 consecutive days ) and 109 were given corresponding saline treatment . Using a variety of objective scoring systems , patients were followed up for up to 6 months . Results At follow-up , all measures of outcome in the treated and control groups were very similar . At 6 months , respective mortality rates were 37 of 107 and 33 of 109 . Corresponding mean±SD improvements in Sc and inavian Stroke Study Group scores were 8.35±16.9 versus 11.55±15.6 ( long-term ) and 0.64±7.3 versus 2.40±6.9 ( prognostic ) , and improvements in the Barthel Index ratings were 10.72±24.7 versus 13.95±23.3 , respectively . Glasgow Coma Scale score improvements in the survivors were 0.81±1.5 and 1.16±1.7 in the treated and control groups , respectively . Hemolysis ( generally sub clinical ) was the only adverse effect of glycerol noted . Conclusions In the absence of any clinical ly or statistically significant difference in outcome between the treated and control groups , this trial provides no justification for glycerol therapy following acute cerebral The effects of intravenous glycerol in elderly patients with recent onset of acute ischaemic stroke were evaluated in a double-blind r and omised controlled trial . 173 patients received either 500 ml of a 10 % solution of glycerol in physiological saline or 500 ml of physiological saline administered intravenously over 4 h daily for 6 consecutive days . The number of deaths within the first week was 10 ( 12 % ) in the glycerol group versus 26 ( 30 % ) in the controls . Subsequent mortality up to 12 months was similar in the two groups and a survival analysis confirmed a beneficial effect of treatment ( p less than 0.02 ) . The neurological and functional recovery of survivors , their length of hospital stay , and the proportion able to return to live in their own home were similar in the two groups . The improvement in survival time with glycerol was achieved without serious adverse effects and without an increase in the proportion of survivors with severe residual disability 10 percent glycerol was given for 6 days to 30 patients who had had acute ischaemic cerebral infa rct ion , and the results were compared with those obtained after treating 31 similar patients with dexamethasone ( 16 mg . per 24 hours for 6 days ) . 1 patient treated with glycerol died of haemoglobinuria and acute renal failure . 6 patients treated with dexamethasone died--3 from cerebral oedema and 3 from non-neurological complications ( pulmonary embolism , myocardial infa rct ion , and aspiration pneumonia ) . Improvement was significantly greater in the glycerol group after 8 and 15 days . No improvement was noted using either glycerol or dexamethasone in 7 patients with spontaneous intracerebral haemorrhage Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews In a prospect i ve , community-based study of 675 consecutive patients with a first-ever stroke , of whom over 90 % had computed tomography ( CT ) and /or necropsy examinations , 129 deaths occurred within 30 days of the onset of symptoms , a case fatality rate ( CFR ) of 19 % . The 30 day CFR for patients with cerebral infa rct ion was 10 % ( 57 of 545 , for primary intracerebral haemorrhage 52 % ( 34 of 66 ) , for subarachnoid haemorrhage 45 % ( 15 of 33 ) and for those of uncertain pathological type 74 % ( 23 of 31 ) . The CFR for patients who had been functionally dependent pre-stroke was 33 % compared with 17 % for those who had been independent pre-stroke . The age-adjusted relative risk of death for patients who had been functionally dependent pre-stroke was not significantly greater ( 1.8 , 95 % confidence interval 0 to 4.3 ) . There was a significant trend for CFR to increase with age ( Chi square for trend = 4.0 , p less than 0.05 ) . This relationship was found in those patients who had been functionally independent prestroke ( Chi square for trend = 7.9 , p less than 0.005 ) but not in those who had been dependent pre-stroke ( Chi square for trend = 0.5 , NS ) . The pattern of increasing CFR with increasing age amongst those who had been independent prestroke was seen particularly in patients with cerebral infa rct ion ( Chi square for trend = 8.6 , p less than 0.005 ) . The age-adjusted relative risk of death for patients with cerebral infa rct ion who had been functionally dependent pre-stroke was 2.2 ( 95 % confidence interval 1.2 to 4.1 ) . Fifty three percent of all deaths within 30 days of stroke were due to the direct neurological sequelae of the stroke . Patients with primary intracerebral or subarachnoid haemorrhages were significantly more likely to die in this way than those with cerebral infa rct ion ( relative risk 4.1 ; 95 % confidence interval 3.4 - 4.9 ) and 56 % of such deaths occurred within 72 hours of onset . In patients with cerebral infa rct ion , 51 % of deaths were due to complications of immobility ( for example , pneumonia , pulmonary embolism ) and these were more likely to occur after the first week . These findings have implication s for clinical practice and the planning of clinical trials |
1,699 | 16,510,881 | A number of advantages of BI suggest they are well suited for translating behavioral research .
In addition , findings from 13 systematic review s of BI effects show their potential versatility . | The purpose of this article is to examine the potential of brief intervention ( BI ) as a modality for translating health behavior intervention research into practice .
We discuss common definitions of BI , applications within common models of translation research , effects of BI on a range of health behaviors and across various population s , current and potential mechanisms , and uses for dissemination to practice . | AIMS Despite widespread prevention efforts to decrease adolescent risk-taking , substance use and driving after drinking ( DD ) are prevalent in the United States . The current study compared the efficacy of an abbreviated version of Drug Abuse and Resistance Education ( DARE-A ) to a new Risk Skills Training Program ( RSTP ) . DESIGN Adolescent participation in drinking , drug use , DD and riding with a drunk driver was examined longitudinally . After baseline assessment s , adolescents were r and omly assigned to the RSTP . DARE-A or a no intervention control group and then completed 2-month post-test and 6-month follow-up assessment s. SETTING Adolescents attended a mid-sized suburban high school . PARTICIPANTS The sample ( N = 300 ) was comprised of 58 % females and the age range was 14 - 19 years . INTERVENTION The RSTP was developed to target several risk behaviors and to examine the feasibility of conducting a brief personalized prevention program in a group setting . DARE-A focused on increasing knowledge and underst and ing the deleterious effects of substance use . MEASUREMENTS Risk-taking behavior , perception of peer risk-taking and positive and negative alcohol expectancies were assessed . FINDINGS RSTP participants decreased participation in several risk behaviors at post-test , but reductions were not maintained at 6-month follow-up . The control and DARE-A groups increased their positive and decreased their negative alcohol expectancies . The control group increased their alcohol consumption . CONCLUSIONS Results suggest that a brief , personalized , group prevention program is a feasible approach to reducing adolescent risk-taking . Strategies must be developed to solidify these positive changes so that they are longer-lasting Abstract Objective : To evaluate the effectiveness of combinations of three methods to promote physical activity . Design : R and omised controlled trial . Baseline assessment with post-intervention follow up at 12 weeks and 1 year . Setting : One urban general practice , 1995 - 7 . Participants : 523 adults aged 40 to 64 years , r and omised to four intervention groups and a control group . Interventions : Brief ( one interview ) or intensive ( six interviews over 12 weeks ) motivational interviewing based on the stages of change model of behaviour change , with or without financial incentive ( 30 vouchers entitling free access to leisure facilities ) . Main outcome measures : Physical activity score ; sessions of moderate and vigorous activity in the preceding four weeks . Results : Response rate was 81 % at 12 weeks and 85 % at one year . More participants in the intervention group reported increased physical activity scores at 12 weeks than controls ( 38 % v 16 % , difference 22 % , 95 % confidence interval for difference 13 % to 32 % ) , with a 55 % increase observed in those offered six interviews plus vouchers . Vigorous activity increased in 29 % of intervention participants and 11 % of controls ( difference 18 % , 10 % to 26 % ) , but differences between the intervention groups were not significant . Short term increases in activity were not sustained , regardless of intensity of intervention . Conclusions : The most effective intervention for promoting adoption of exercise was the most intensive . Even this did not promote long term adherence to exercise . Brief interventions promoting physical activity that are used by many schemes in the United Kingdom are of question able effectiveness . Key messages Schemes promoting physical activity are currently popular in general practice in Britain , but few have been rigorously evaluated and their effectiveness is unknown . In this study , the most effective intervention for promoting adoption of physical activity was the most intensive , involving six motivational interviews and a financial incentive A comparatively brief intervention ( one interview ) was only effective in the short term in around a third of participants Short term increases in physical activity were not maintained at one year follow up and even the most intensive intervention was ineffective in promoting long term adherence to increased physical activity . National and local government , health authorities , and primary healthcare teams should be cautious about current and future expenditure on , and implementation of , exercise prescription or referral OBJECTIVES Message tailoring , based on individual needs and circumstances , is commonly used to enhance face-to-face patient counseling . Only recently has individual tailoring become feasible for printed messages . This study sought to determine whether printed tailored recommendations addressing women 's specific screening and risk status and perceptions about breast cancer and mammography are more effective than st and ardized printed recommendations . METHODS Computer-assisted telephone interviews were conducted with 435 women , aged 40 to 65 years , who had visited family practice groups within the previous 2 years . Subjects were r and omly allocated to receive individually tailored or st and ardized mammography recommendation letters mailed from physicians to patients ' homes . Follow-up interviews were conducted 8 months later . RESULTS Tailored letter recipients were more likely to remember and to have read more of their letters than st and ardized version recipients . After controlling for baseline status , tailored letter receipt was associated with more favorable follow-up mammography status for women with incomes below $ 26,000 and for Black women . CONCLUSIONS Tailored messages are a more effective medium for physicians ' mammography recommendations ; tailoring may be especially important for women of low socioeconomic status OBJECTIVES To examine the efficacy of UV photographs and information about photoaging ( eg , wrinkles and age spots ) for increasing the sun protection intentions and behaviors of young adults and to determine whether any effects of this appearance-based intervention could be enhanced by providing a non-UV alternative for achieving a tan ( ie , sunless tanning lotion ) . DESIGN R and omized control trial with 1-month follow-up . SETTING Two universities in Southern California . PARTICIPANTS A volunteer sample of 146 college students , 91.1 % of whom completed the " surprise " 1-month follow-up . INTERVENTION A UV facial photograph and a brief videotape describing the causes and consequences of photoaging . The study tested the effects of the photoaging information/UV photographic intervention only , the intervention plus use of sunless tanning lotion , and a control condition . MAIN OUTCOME MEASURES Participants sun protection intentions as assessed immediately after the intervention and sun protection behaviors during the month after the intervention as assessed during a surprise telephone follow-up . RESULTS The intervention result ed in significantly stronger sun protection intentions ( P<.001 ) and greater sun protection behaviors ( P<.05 ) relative to controls . Furthermore , the group that also used sunless tanning lotion tended to engage in greater sun protection behaviors than the group that received the intervention alone ( P<.08 ) . CONCLUSION The UV photographic intervention holds promise as a cost-effective approach to motivate practice s that may ultimately result in health benefits ( ie , reduced skin cancer rates ) Testing behavioral interventions to increase safer sex practice s of HIV+ individuals has the potential to significantly reduce the number of new infections . This study evaluated a behavioral intervention design ed to reduce the sexual risk behaviors of HIV+ individuals . HIV+ individuals ( N = 387 ) who reported engaging in unprotected sex with HIV- or partners of unknown serostatus were r and omly assigned to ( a ) a single counseling session targeting problem areas identified by the participant in 3 possible intervention domains ( i.e. , condom use , negotiation , disclosure ) ; ( b ) a single-session comprehensive intervention that covered all 3 intervention domains ; ( c ) the same comprehensive intervention , plus 2 monthly booster sessions ; or ( d ) a 3-session diet and exercise attention-control condition . The median number of unprotectedsex acts decreasedfrom 14 at baseline to6 , 6 , and 4 at 4- , 8- , and 12-month follow-ups , respectively . A repeated measures analysis of variance revealed a significant decrease in unprotected sex acts across all groups across time . A significant Group x Time interaction revealed that the comprehensive-with-boosters group had the most unprotected sex at 8-month follow-up as compared to the other 3 groups . These findings suggest that a brief intervention can result in large reductions in HIV transmission risks among HIV+ individuals , but the relative benefit of one intervention approach over another remains unclear The authors investigated the efficacy of an interactive Web site , MyStudentBody.com : Alcohol ( MSB : Alcohol ) that offers a brief , tailored intervention to help heavy drinking college students reduce their alcohol use . They conducted a r and omized , controlled clinical trial to compare the intervention with an alcohol education Web site at baseline , postintervention , and 3-month follow-up . Students were assessed on various drinking measures and their readiness to change their drinking habits . The intervention was especially effective for women and persistent binge drinkers . Compared with women who used the control Web site , women who used the intervention significantly reduced their peak and total consumption during special occasions and also reported significantly fewer negative consequences related to drinking . In addition , persistent heavy binge drinkers in the experimental group experienced a more rapid decrease in average consumption and peak consumption compared with those in the control group . The authors judged MSB : Alcohol a useful intervention for reaching important subgroups of college binge drinkers Motivational interviewing offers health care professionals a potentially effective strategy for increasing a patient 's readiness to change health behaviors . Recently , elements of motivational interviewing and the stages of change model have been simplified and adapted for use with patients in brief clinical encounters . This paper describes in detail a brief motivational intervention model to improve and renew dietary adherence with adolescents in the Dietary Intervention Study in Children ( DISC ) . DISC is a r and omized , multi-center clinical trial assessing the efficacy and safety of lowering dietary fat to decrease low-density lipoprotein cholesterol in high-risk children . In the first 3 years of follow-up covering ages 8 - 13 , intervention participants ( n = 334 ) were exposed to a family-based group intervention approach to change dietary choices . To address adherence and retention obstacles as participants moved into adolescence ( age 13 - 17 ) , an individual-level motivational intervention was implemented . The DISC motivational intervention integrates several intervention models : stages of change , motivational interviewing , brief negotiation and behavioral self-management . A preliminary test of the intervention model suggests that it was acceptable to the participants , popular with interventionists and appeared to be an age-appropriate shift from a family-based intervention model AIMS This clinical trial investigated effects of motivational enhancement treatment ( MET ) and group coping-skills training ( CST ) tailored for cocaine dependence . Effects of MET were hypothesized to be greater with CST and for less motivated patients . DESIGN AND INTERVENTIONS A 2 x 2 design investigated two individual sessions of MET compared to meditation-relaxation ( MRT ) , followed by four group sessions of CST versus drug education ( ED ) , as daily adjuncts to intensive treatment . SETTING The substance abuse program provided full-day treatment with a learning-theory and 12-Step orientation . PARTICIPANTS Cocaine-dependent patients were recruited . MEASUREMENTS Assessment included treatment retention ; change in cocaine-related urge , self-efficacy , pros and cons , and motivation ; substance use and problems during 12-month follow-up . Findings Of 165 patients , follow-up status is known for 90 % ( n = 149 ) . Patients in MET with low initial motivation to change reported less cocaine and alcohol relapse and use days and fewer alcohol problems than MET patients with higher initial motivation . MET produced more employment improvement than MRT , with no other significant benefit for MET . Patients with higher motivation had more cocaine use and alcohol problems after MET than MRT . Group CST reduced cocaine and alcohol use during follow-up for women only and reduced alcohol relapse for men and women . CONCLUSIONS MET is more beneficial for patients with lower initial motivation than for patients with high initial motivation . CST reduced cocaine and alcohol use for women only and reduced alcohol relapses , in contrast to results with lengthier individual CST OBJECTIVE The current study examined the efficacy of mailed personalized normative feedback ( PNF ) as a brief alcohol intervention for at-risk college drinkers , and investigated discrepancy as a possible mediator of the intervention effect . METHOD Participants consisted of 100 at-risk college drinkers who completed an alcohol-use assessment at baseline , 6-week posttest and 6-month follow-up . Measures included number of drinks consumed per heaviest drinking week , frequency of heavy-drinking episodes , peak blood alcohol concentration and number of alcohol-related problems , all for the last month . Participants were r and omly assigned to either a mailed brief intervention ( MBI ; n = 49 ) or attention-control ( C ; n = 51 ) group . The MBI group received mailed PNF that was based on baseline responses to the drinking measures ; the C group received a psychoeducational brochure about alcohol . RESULTS Mixed-model , repeated measures ANOVAs were used to examine the effects of time , group and gender on discrepancy and the drinking variables . Following the intervention , the MBI group reported significantly higher perceived discrepancy between self and others ' drinking than the C group . The MBI group reported consuming significantly fewer drinks per heaviest drinking week and engaging in heavy episodic drinking less frequently than the C group at the 6-week posttest ; however , these differences were no longer evident at the 6-month follow-up . Hierarchical regression analyses did not provide evidence for the hypothesized mediating effect of discrepancy . CONCLUSIONS Mailed PNF may be a cost- and time-efficient means of developing discrepancy and temporarily reducing heavy alcohol consumption among at-risk college drinkers OBJECTIVE Comorbidity of substance abuse disorders with schizophrenia is associated with a greater risk for serious illness complications and poorer outcome . Method ologically sound studies investigating treatment approaches for patients with these disorders are rare , although recommendations for integrated and comprehensive treatment programs abound . This study investigates the relative benefit of adding an integrated psychological and psychosocial treatment program to routine psychiatric care for patients with schizophrenia and substance use disorders . METHOD The authors conducted a r and omized , single-blind controlled comparison of routine care with a program of routine care integrated with motivational interviewing , cognitive behavior therapy , and family or caregiver intervention . RESULTS The integrated treatment program result ed in significantly greater improvement in patients ' general functioning than routine care alone at the end of treatment and 12 months after the beginning of the study . Other benefits of the program included a reduction in positive symptoms and in symptom exacerbations and an increase in the percent of days of abstinence from drugs or alcohol over the 12-month period from baseline to follow-up . CONCLUSIONS These findings demonstrate the effectiveness of a program of routine care integrated with motivational interviewing , cognitive behavior therapy , and family intervention over routine psychiatric care alone for patients with comorbid schizophrenia and alcohol or drug abuse or dependence Two brief treatments for problem gambling were compared with a waiting-list control in a r and omized trial . Eighty-four percent of participants ( N = 102 ) reported a significant reduction in gambling over a 12-month follow-up period . Participants who received a motivational enhancement telephone intervention and a self-help workbook in the mail , but not those who received the workbook only , had better outcomes than participants in a 1-month waiting-list control . Participants who received the motivational interview and workbook showed better outcomes than those receiving the workbook only at 3- and 6-month follow-ups . At the 12-month follow-up , the advantage of the motivational interview and workbook condition was found only for participants with less severe gambling problems . Overall , these results support the effectiveness of a brief telephone and mail-based treatment for problem gambling The chameleon effect refers to nonconscious mimicry of the postures , mannerisms , facial expressions , and other behaviors of one 's interaction partners , such that one 's behavior passively and unintentionally changes to match that of others in one 's current social environment . The authors suggest that the mechanism involved is the perception-behavior link , the recently documented finding ( e.g. , J. A. Bargh , M. Chen , & L. Burrows , 1996 ) that the mere perception of another 's behavior automatically increases the likelihood of engaging in that behavior oneself . Experiment 1 showed that the motor behavior of participants unintentionally matched that of strangers with whom they worked on a task . Experiment 2 had confederates mimic the posture and movements of participants and showed that mimicry facilitates the smoothness of interactions and increases liking between interaction partners . Experiment 3 showed that dispositionally empathic individuals exhibit the chameleon effect to a greater extent than do other people A stage-matched expert system intervention was evaluated on 4144 smokers in a two-arm r and omized control trial with four follow-ups over 24 months . Smokers were recruited by r and om digit-dial calls , and 80.0 % of the eligible smokers were enrolled . Individualized and interactive expert system computer reports were sent at 0 , 3 , and 6 months . The reports provided feedback on 15 variables relevant for progressing through the stages . The primary outcomes were point prevalence and prolonged abstinence rates . At 24 months , the expert system result ed in 25.6 % point prevalence and 12 % prolonged abstinence , which were 30 % and 56 % greater than the control condition . Abstinence rates at each 6-month follow-up were significantly greater in the Expert System ( ES ) condition than in the comparison condition with the absolute difference increasing at each follow-up . A proactive home-based stage-matched expert system smoking cessation program can produce both high participation rates and relatively high abstinence rates OBJECTIVES The aim of the present study was to develop , implement and evaluate a brief intervention to improve adherence to the recommended lifestyle changes for patients with Type 2 diabetes , in particular to help patients to reduce the total amount of fat consumed and to increase lifestyle physical activity levels . DESIGN AND METHOD A brief , tailored lifestyle self-management intervention for patients with Type 2 diabetes was evaluated in a r and omized controlled trial . One hundred participants ( aged 40 - 70 yrs ) completed assessment s at three time points- baseline , three months and one year . Participants were allocated to either an intervention group who received the brief tailored intervention including follow-up telephone calls , or a usual care control group . RESULTS Results indicate that the intervention was successful in helping patients to reduce fat intake and , to a lesser extent , increase lifestyle physical activity levels . These self-reported changes in behaviour were reflected in the objective data with weight maintenance in the intervention group compared to the control group , together with a significant reduction ( 2 cm ) in waist circumference . CONCLUSIONS These results provide further evidence of the effectiveness of tailored interventions for lifestyle change The primary purpose of this study was to test the efficacy of a brief , multi-health behavior intervention integrating physical activity and alcohol use prevention messages for high school-aged adolescents . A total of 604 participants , 335 9th and 269 11th grade students from a suburban high school in northeast Florida participated in this study . A r and omized control trial was conducted with participants r and omly assigned within grade levels to receive either a brief consultation and prescription with a mailed reinforcing follow-up flyer ( Project SPORT ) or a minimal intervention control consisting of a wellness brochure provided in school and a pamphlet about teen health and fitness mailed to the home . Differences between intervention groups were evaluated with a series of MANCOVA tests . Project SPORT participants demonstrated significant positive effects at 3-months postintervention for alcohol consumption , alcohol initiation behaviors , alcohol use risk and protective factors , drug use behaviors , and exercise habits , and at 12-months for alcohol use risk and protective factors , cigarette use , and cigarette initiation ( p 's < 0.05 ) . A post hoc analysis examining interactions between past 30-day use of marijuana and /or cigarettes by treatment group indicates significant positive effects for drug using adolescents who received Project SPORT on alcohol consumption , drug use behaviors , and drug use initiation at 3-months , and for drug use behaviors and exercise habits at 12-months ( p 's < 0.05 ) . A brief , 12-min one-on-one consultation integrating alcohol avoidance messages within those promoting fitness and other positive health behaviors holds promise for influencing adolescent alcohol and cigarette use and other health behaviors at posttreatment and 1 year later . Long-term sustained effects for cigarette and marijuana use , and both vigorous and moderate physical activity , were found among adolescents using marijuana and /or cigarettes prior to intervention BACKGROUND Evidence suggests that preoperative clinics , like other hospital outpatient clinics and inpatient wards , fail to systematic ally provide smoking cessation care to patients having planned surgery . METHODS The aim of the study was to assess the efficacy , acceptability , and cost of a multifaceted intervention to facilitate the provision of comprehensive smoking cessation care to patients attending a preoperative clinic . Two hundred ten smoking patients attending a preoperative clinic at a major teaching hospital in Australia took part in the study . One hundred twenty-four patients were r and omly assigned to an experimental group and 86 patients to a usual cessation care group . A multifaceted intervention was developed that included the use of opinion leaders , consensus processes , computer-delivered cessation care , computer-generated prompts for care provision by clinic staff , staff training , and performance feedback . RESULTS Ninety-six percent of experimental group patients received behavioral counseling and tailored self-help material . Experimental group patients were significantly more likely than usual care patients to report receiving brief advice by nursing ( 79 % vs. 47 % ; P < 0.01 ) and anaesthetic ( 60 % vs. 39 % ; P < 0.01 ) staff . Experimental group patients who were nicotine dependent were also more likely to be offered preoperative nicotine replacement therapy ( NRT ) ( 82 % vs. 8 % ; P < 0.01 ) and be prescribed postoperative NRT ( 86 % vs. 0 % ; P < 0.01 ) . The multifaceted intervention was found to be acceptable by staff . CONCLUSION A multifaceted clinical practice change intervention may be effective in improving the delivery of smoking cessation care to preoperative surgical patients Thirty-one self-referred problem drinkers were r and omly assigned to one of two modalities for behavioral self-control training with a goal of moderation : ( 1 ) minimal therapist contact , in which clients worked only with a self-help manual ; and ( 2 ) therapist directed training , in which clients received self-help material s plus 10 individual treatment sessions . Both groups showed significant reductions in alcohol consumption and peak blood alcohol concentration . Contrary to expectations , there were no significant differences on outcome measures between groups . Results are interpreted within a self-control framework This r and omized controlled trial evaluated the efficacy of a brief intervention design ed to reduce the harmful consequences of heavy drinking among high-risk college students . Students screened for risk while in their senior year of high school ( 188 women and 160 men ) were r and omly assigned to receive an individualized motivational brief intervention in their freshman year of college or to a no-treatment control condition . A normative group selected from the entire screening pool provided a natural history comparison . Follow-up assessment s over a 2-year period showed significant reductions in both drinking rates and harmful consequences , favoring students receiving the intervention . Although high-risk students continued to experience more alcohol problems than the natural history comparison group over the 2-year period , most showed a decline in problems over time , suggesting a developmental maturational effect BACKGROUND Results are reported from a large r and omized trial design ed to increase fruit and vegetable consumption among callers to the National Cancer Institute 's Cancer Information Service ( CIS ) ( n = 1,717 ) . METHODS CIS callers assigned to the intervention group ( n = 861 ) received a brief proactive educational intervention over the telephone at the end of usual service , with two follow-up mailouts . Key educational messages and print material derived from the NCI 5 A Day for Better Health program were provided to intervention participants . Participants were interviewed by telephone at 4 weeks ( n = 1,307 ) , 4 months ( n = 1,180 ) , and 12 months for follow-up ( n = 1,016 ) . RESULTS Results obtained from a single-item measure of fruit and vegetable consumption indicate a significant intervention effect of 0.88 servings per day at 4 weeks follow-up ( P < 0.001 ) , 0.63 servings per day at 4 months follow-up ( P < 0.001 ) , and 0.43 servings per day at 12 months follow-up ( P < 0.001 ) . Using a 7-item food frequency measure , an intervention effect of 0.63 servings per day was obtained at 4 weeks follow-up ( P < 0.001 ) , compared with 0.39 servings per day at 4 months follow-up ( P = 0.002 ) and 0.44 servings per day at 12 months follow-up ( P = 0.002 ) . A 24-h recall assessment included in the 4-month interviews also yielded a significant intervention effect of 0.67 servings per day ( P = 0.015 ) . The vast majority of callers ( 90 % ) endorsed the strategy of providing 5 A Day information proactively within the CIS . CONCLUSIONS This brief educational intervention was associated with higher levels of self-reported fruit and vegetable intake at both short- and long-term follow-up . Additional research is recommended to test this or a similar intervention in diverse population This study tested the potential of a novel intervention addressing alcohol prevention within the context of a sport program . Study participants were r and omly assigned to one of three groups , with one group receiving the sport consultation ( Sport ) , a second the sport consultation plus an alcohol consultation ( Sport Plus ) , and a third a sport consultation , alcohol consultation , and mailed parent print material s ( Sport Plus Parent ) . Research ers recruited 465 eighth grade rs from three schools in the northeast Florida region to participate in the study . The Youth Alcohol and Health Survey was used to collect data on alcohol and drug consumption , alcohol use risk and protective factors , and exercise habits at baseline and three-month post-intervention . Significant time effects ( p 's < .05 ) were found on three of six alcohol measures , both exercise measures , and four risk/protective factors , with all but one risk factor showing improvements over time . Time by assignment by current drinking status ( yes/no ) interaction effects ( p 's < .05 ) were found on alcohol initiation , length of alcohol use , quantity , heavy use , moderate physical activity , and four risk/protective factors , with preintervention drinking adolescents exposed to the Sport intervention showing the greatest improvements on all but two measures . Findings suggest that a brief sport-based screen and consultation tailored to adolescents ' health habits , with and without parent material s , may potentially reduce alcohol use while increasing exercise frequency Reducing the prevalence of adolescent cigarette smoking and alcohol drinking are public health goals of the United States . Although families have strong influence on their children , few r and omized studies have examined whether family-directed programs influence those behaviors in general universal population s. This paper reports findings from an evaluation of a family program that features the mailing of four booklets to adult family members with follow-up telephone calls by health educators . A national sample of adolescent – parent pairs and a r and omized experimental design were used to evaluate the program . Baseline users and nonusers of those substances were considered simultaneously in analyses so that program influences on smoking and drinking prevalence could be examined . The findings suggest that the program significantly reduced the prevalence of smoking cigarettes and drinking alcohol among adolescents . These findings are discussed in the context of earlier reports of research on the family program and implication s for public health BACKGROUND Public health dental clinic patients use tobacco at disproportionately high rates . The purpose of this study was to evaluate a tobacco-use cessation program delivered via public health dental practitioners . METHODS Two public health dental clinics participated in this quasiexperimental design study . First , all patients in one clinic who used tobacco ( n = 178 ) received usual care . Next , the authors trained all practitioners to conduct a tobacco-use assessment and provide a brief cessation intervention . Subsequently , all patients in both clinics who used tobacco ( N = 190 ) received the intervention . All enrolled patients had an income at or below the federal poverty level . The authors conducted follow-up assessment s at six weeks and three and six months after enrollment . RESULTS Differences in self-reported quitting by condition between participants in the two groups were significant across all endpoints . Patients in the intervention group were more likely to quit than those receiving usual care ( 15.5 versus 4.3 percent ) and after 12 months ( 18.8 versus 4.6 percent ) . Controlling for enrollment differences between patients in the two groups ( age , race/ethnicity , time to first cigarette after waking ) , the authors found that differences between groups were significant for quitting at three months ( P < .05 ; odds ratio [ OR ] = 4.85 ; 95 percent confidence interval [ CI ] = 1.20 , 19.60 ) , and six months ( P < . 01 ; OR = 5.25 ; 95 percent CI = 1.35 , 20.36 ) . CONCLUSIONS The results of this study suggest the viability and effectiveness of delivering a tobacco intervention to low-income smokers via public dental practitioners . A r and omized clinical trial is warranted . CLINICAL IMPLICATION S The potential reach of public health dental clinics is great . Because of the high percentage of tobacco-using patients in these clinics , the public health impact of a program such as the one reported here would be significant Problem drinking is common among patients in primary medical care , but often unrecognized . Brief physician interventions can be helpful , but several barriers hinder their adoption in practice , notably a lack of time . We conducted a r and omized pilot study of written behavioral contracts that patients wrote with help from a computer program . In eight family medicine practice s , 2684 patients were approached and 2399 screened with the Alcohol Use Disorders Identification Test ( AUDIT ) . Of those , 186 screened positive , 154 were eligible , and 80 enrolled . Follow‐up interviews were completed with 69 ( 86 % ) . At 12 months , the AUDIT and Addiction Severity Index alcohol scores decreased nonsignificantly more in the intervention group than in the controls . The study demonstrated that computer‐based interventions are acceptable to patients and physicians , feasible in busy primary care practice s , and have effect sizes comparable to those of physician‐based interventions . Computer‐based interventions may be an effective and efficient tool to enhance identification of and intervention with problem drinkers in primary care Abstract The effectiveness of 4 alternative forms of behavioral self-control training ( BSCT ) design ed to reduce alcohol consumption was evaluated . Forty-one problem drinkers were assigned to 1 of 4 treatment conditions : ( a ) bibliotherapy , in which clients were evaluated and then provided with a self-help manual ( Miller & Munoz , 1976 ) and self-monitoring cards but were not given therapy sessions , ( b ) BSCT alone , consisting of 10 individual sessions following material presented in the manual , ( c ) BSCT plus relaxation training , being identical to ( b ) except that training in progressive deep muscle relaxation was added within the 10 sessions , and ( d ) group therapy identical in content to ( c ) but offered in a group rather than in individual format . Outcome data included information from client interviews , psychometric measures , self-monitoring cards , and interviews with significant others . All data sources indicated significant and substantial reduction in alcohol consumption , particularly in “ alcoholismic ” drinking patterns . No significant differences were found among the 4 treatment groups . The cost-effectiveness of a bibliotherapy approach was supported , consistent with prior research . Overall improvement rates were 84 % and 69 % at 3- and 12-month follow-up , respectively BACKGROUND Brief intervention is effective for alcohol misuse , but not adequately tested in the clinical setting with drug using patients . This study tested the impact of a single , structured encounter targeting cessation of drug use , conducted between peer educators and out-of-treatment cocaine and heroin users screened in the context of a routine medical visit . METHODS A r and omized , controlled trial was conducted in inner-city teaching hospital outpatient clinics with 3 and 6 months follow-up by blinded observers . Drug abstinence was documented by RIA hair testing . Analysis was limited to enrollees with drug-positive hair at baseline . RESULTS Among 23,669 patients screened 5/98 - 11/00 , 1232 ( 5 % ) were eligible , and 1175 enrolled . Enrollees ( mean age 38 years ) were 29 % female , 62 % non-hispanic black , 23 % hispanic , 46 % homeless . Among those with positive hair at entry , the follow-up rate was 82 % . The intervention group was more likely to be abstinent than the control group for cocaine alone ( 22.3 % versus 16.9 % ) , heroin alone ( 40.2 % versus 30.6 % ) , and both drugs ( 17.4 % versus 12.8 % ) , with adjusted OR of 1.51 - 1.57 . Cocaine levels in hair were reduced by 29 % for the intervention group and only 4 % for the control group . Reductions in opiate levels were similar ( 29 % versus 25 % ) . CONCLUSIONS Brief motivational intervention may help patients achieve abstinence from heroin and cocaine Objective . To test the long-term efficacy of brief counseling plus a computer-based tobacco intervention for teens being seen for routine medical care . Methods . Both smoking and nonsmoking teens , 14 to 17 years of age , who were being seen for routine visits were eligible for this 2-arm controlled trial . Staff members approached teens in waiting rooms of 7 large pediatric and family practice departments within a group- practice health maintenance organization . Of 3747 teens invited at ≥1 visits , 2526 ( 67 % ) consented and were r and omized to tobacco intervention or brief dietary advice . The tobacco intervention was individually tailored on the basis of smoking status and stage of change . It included a 30-second clinician advice message , a 10-minute interactive computer program , a 5-minute motivational interview , and up to two 10-minute telephone or in-person booster sessions . The control intervention was a 5-minute motivational intervention to promote increased consumption of fruits and vegetables . Follow-up smoking status was assessed after 1 and 2 years . Results . Abstinence rates after 2 years were significantly higher for the tobacco intervention arm , relative to the control group , in the combined sample of baseline smokers and nonsmokers ( odds ratio [ OR ] : 1.23 ; 95 % confidence interval [ CI ] : 1.03–1.47 ) . Treatment effects were particularly strong among baseline self-described smokers ( OR : 2.42 ; 95 % CI : 1.40–4.16 ) but were not significant for baseline nonsmokers ( OR : 1.25 ; 95 % CI : 0.97–1.61 ) or for those who had “ experimented ” in the past month at baseline ( OR : 0.95 ; 95 % CI : 0.45–1.98 ) . Conclusions . Brief , computer-assisted , tobacco intervention during routine medical care increased the smoking cessation rate among self-described smokers but was less effective in preventing smoking onset This study examined whether indicators of drug-related memory associations predicted drug use prospect ively . The predictive effects of outcome expectancies , sensation seeking , and other variables also were investigated . The results revealed that the memory association measures significantly predicted subsequent drug use . Outcome expectancies and sensation seeking predicted alcohol use , but not marijuana use . The findings suggest 2 possibly different aspects of cognition involved in drug use motivation : ( a ) a memory activation or implicit cognition component , representing the effects of memory associations that are prompted relatively spontaneously by the prevailing motivational and situational circumstances and ( b ) an outcome expectancy component , which is more likely to reflect explicit cognitions involved in introspection and deliberate decision-making processes OBJECTIVES The relative effects of simple advice and brief counseling were evaluated with heavy drinkers identified in primary care and other health setting s in eight countries . METHODS Subjects ( 1260 men , 299 women ) with no prior history of alcohol dependence were selected if they consumed alcohol with sufficient frequency or intensity to be considered at risk of alcohol-related problems . Subjects were r and omly assigned to a control group , a simple advice group , or a group receiving brief counseling . Seventy-five percent of subjects were evaluated 9 months later . RESULTS Male patients exposed to the interventions reported approximately 17 % lower average daily alcohol consumption than those in the control group . Reductions in the intensity of drinking were approximately 10 % . For women , significant reductions were observed in both the control and the intervention groups . Five minutes of simple advice were as effective as 20 minutes of brief counseling . CONCLUSIONS Brief interventions are consistently robust across health care setting s and sociocultural groups and can make a significant contribution to the secondary prevention of alcohol-related problems if they are widely used in primary care This study evaluated the use of a brief motivational interview ( MI ) to reduce alcohol-related consequences and use among adolescents treated in an emergency room ( ER ) following an alcohol-related event . Patients aged 18 to 19 years ( N = 94 ) were r and omly assigned to receive either MI or st and ard care ( SC ) . Assessment and intervention were conducted in the ER during or after the patient 's treatment . Follow-up assessment s showed that patients who received the MI had a significantly lower incidence of drinking and driving , traffic violations , alcohol-related injuries , and alcohol-related problems than patients who received SC . Both conditions showed reduced alcohol consumption . The harm-reduction focus of the MI was evident in that MI reduced negative outcomes related to drinking , beyond what was produced by the precipitating event plus SC alone OBJECTIVE The objective of this study was to develop and test a brief , experimental alcohol preventive intervention matched to the use of specific alcohol beverages among adolescents . METHOD A total of 232 high school students who drank within the last year participated in this study . Participants were r and omly assigned to either the experimental intervention or a minimal intervention control . Four-month postintervention data are reported . RESULTS Overall multivariate analyses of covariance ( MANCOVAs ) were significant ( p 's < .05 ) on risk factors ( influenceability , perceived severity , perceived susceptibility and perceived peer prevalence ) for three of six beverages ( beer , wine and distilled spirits ) , with a fourth , malt liquor , approaching significance ( p = .06 ) . These tests showed intervention adolescents experiencing less risk for alcohol use than control adolescents . In addition , whereas the overall MANCOVA for malt liquor use was not significant , univariate analyses were significant for 30-day frequency ( F = 5.69 , 1/195 df , p = .01 ) and 30-day quantity of malt liquor use ( F = 4.03 , 1/195 df , p = .04 ) with intervention adolescents showing less consumption than control adolescents . A post hoc analysis examining differential intervention effects using preintervention drug use as a factor ( i.e. , 30-day cigarette or marijuana use ) showed a significant overall factorial MANCOVA interaction ( F = 6.90 , 4/189 df , p = .000 ) , with drug-using intervention adolescents consuming cigarettes and marijuana less frequently than drug-using control adolescents at postintervention . CONCLUSIONS The findings of this study suggest the brief , beverage-tailored intervention reduced certain risk factors mediating individual alcohol beverage use and consumption of malt liquor ( 4 months after intervention ) and may have reduced the frequency of cigarette and marijuana use among those already using drugs BACKGROUND Previous interventions to promote performance of cancer prevention activities have largely targeted physicians in university-based practice s. METHODS We r and omly assigned 40 primary care physicians in community-based practice s to either ( 1 ) Cancer Prevention Reminders , computer-generated lists of overdue screening tests , and smoking and dietary assessment and counseling , supplemented by cancer education material s ; or ( 2 ) controls . For each physician , we review ed a r and om sample of 60 medical records for data about screening test , assessment , and counseling performance during 12-month preintervention and intervention periods . We calculated performance scores as percentage compliance with American Cancer Society and /or National Cancer Institute recommendations . Multiple regression analyses provided estimates of incremental differences in performance scores between intervention and control groups . RESULTS Controlling for preintervention performance levels , significant incremental differences in performance scores between intervention and control groups ( P less than .05 ) were achieved for nine maneuvers : stool occult-blood test , + 14.5 ; rectal examination , + 10.5 ; pelvic examination , + 11.8 ; Papanicolaou 's smear , + 30.7 ; breast examination , + 8.7 ; smoking assessment , + 10.2 ; smoking counseling , + 17.3 ; dietary assessment , + 12.3 ; and dietary counseling , + 13.9 . Increments for sigmoidoscopy and mammography were not significant . CONCLUSION Computerized reminders can significantly increase physicians ' performance of cancer prevention activities in community-based practice Abstract Objective To assess the effect of brief interventions during the “ watchful waiting ” period for hypertension . Design Factorial trial . Setting General practice . Methods 296 patients with blood pressure > 160/90 mm Hg were r and omised to eight groups defined by three factors : an information booklet ; low sodium , high potassium salt ; prompt sheets for high fruit , vegetable , fibre ; and low fat . Main outcome measures Blood pressure ( primary outcome ) ; secondary outcomes of diet , weight , and dietary biomarkers ( urinary sodium : potassium ( Na : K ) ratio ; carotenoid concentrations ) . Results Blood pressure was not affected by the booklet ( mean difference ( diastolic blood pressure ) at one month 0.2 , 95 % confidence interval 1.6 to 2.0 ) , salt ( 0.13 ; 1.7 to 2.0 ) , or prompts ( 0.52 ; 1.3 to 2.4 ) . The salt decreased Na : K ratio ( difference 0.32 ; 0.08 to 0.56 , P = 0.01 ) , and the prompts helped control weight ( difference 0.39 ( 0.85 to 0.05 ) kg at one month , P = 0.085 ; 1.2 ( 0.1 to 2.25 ) kg at six months , P = 0.03 ) . Among those with lower fruit and vegetable consumption ( < 300 g per day ) , prompts increased fruit and vegetable consumption and also carotenoid concentrations ( difference 143 ( 16 to 269 ) mmol/l , P < 0.03 ) but did not decrease blood pressure . Conclusion During watchful waiting , over and above the effect of brief advice and monitoring , an information booklet , lifestyle prompts , and low sodium salt do not reduce blood pressure . Secondary analysis suggests that brief interventions —particularly lifestyle prompts — can make useful changes in diet and help control weight , which previous research indicates are likely to reduce the long term risk of stroke |
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